tag:blogger.com,1999:blog-58726739301127273452024-03-16T14:49:50.373-04:00Nephron PowerKenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.comBlogger1655125tag:blogger.com,1999:blog-5872673930112727345.post-15551034355824798662024-03-14T06:01:00.002-04:002024-03-14T06:01:17.432-04:00In the News: Dense Deposit Disease and ApoE- the new connection<p>C3 glomerulopathy arises from irregularities in the alternative pathway of complement. It manifests as two types: C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), identifiable by bright C3 staining in the glomeruli under immunofluorescence. EM distinguishes DDD by dense deposits along the glomerular basement membranes, contrasting with non-dense deposits in C3GN. <a href="https://www.kidney-international.org/article/S0085-2538(24)00169-8/fulltext">A fascinating new study</a> investigating 12 cases each of DDD, C3GN, and pretransplant kidney controls, laser microdissection (LCM) followed by mass spectrometry (MS) revealed a significant accumulation of complement proteins and regulatory factors in both C3GN and DDD compared to controls. Notably, DDD exhibited a much higher concentration of C5-9 and apolipoprotein E (ApoE) compared to C3GN. </p><p><br /></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhasisOp7z6iAIBmapFBZC-VxWFIIH0rAg7FMV8RwcN-pgPMELxypGzq6sq23E6Jyv5vurC3BO2UNk9kiPKeSTeHwI0HBga9zgHaOODLY-GW4PRyecD4-hh45nLJyRfSSbSP9YCI8P9IOLUB5wF_lA-_-H_kfs7AivUAkZDDc-6FQgE1xqJNOzJZuOOzlI/s1600/densedepdiseaseLarque08.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="1220" data-original-width="1600" height="244" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhasisOp7z6iAIBmapFBZC-VxWFIIH0rAg7FMV8RwcN-pgPMELxypGzq6sq23E6Jyv5vurC3BO2UNk9kiPKeSTeHwI0HBga9zgHaOODLY-GW4PRyecD4-hh45nLJyRfSSbSP9YCI8P9IOLUB5wF_lA-_-H_kfs7AivUAkZDDc-6FQgE1xqJNOzJZuOOzlI/s320/densedepdiseaseLarque08.jpg" width="320" /></a></div><p><br /></p><p><br /></p><br /><br /><br /><br /><br /><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p>Image courtesy: pathologyoutlines.com </p><p><br /></p><p>ApoE staining aligned with dense deposit patterns in DDD but not in C3GN or controls, validated in 31 C3G cases. This is fascinating as perhaps ApoE staining may serve as a diagnostic tool for DDD, particularly when EM is unavailable, as it reflects the enriched presence of ApoE in dense deposits, distinguishing DDD from C3GN.</p><p><br /></p><p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhic1ZThIMUED12gz06Fkgb9Yurt5DpQdKJqtYAcmunnAenNnXdtXzd4pXr_r2MCO97LSJ5rbSuJsLA8cNdxt74xzYBCMoHJ6C4A5PSc_LMGO2q-zVEs59f2LBUy79Zfcf2_OI0sgPZ8JbP0rDqMWiJnRMG8I7-oWUEr_OFvtPdOHK66JzyiUzK1XmtNko/s1575/ga1_lrg%20(4).jpg" imageanchor="1" style="clear: left; display: inline !important; float: left; margin-bottom: 1em; margin-right: 1em; text-align: center;"><img border="0" data-original-height="886" data-original-width="1575" height="225" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhic1ZThIMUED12gz06Fkgb9Yurt5DpQdKJqtYAcmunnAenNnXdtXzd4pXr_r2MCO97LSJ5rbSuJsLA8cNdxt74xzYBCMoHJ6C4A5PSc_LMGO2q-zVEs59f2LBUy79Zfcf2_OI0sgPZ8JbP0rDqMWiJnRMG8I7-oWUEr_OFvtPdOHK66JzyiUzK1XmtNko/w400-h225/ga1_lrg%20(4).jpg" width="400" /></a><br /><br /></p><br /><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><div>ApoE is a 34 kDa lipoprotein, that facilitates lipid transportation by binding to lipids. As we are aware, in various diseases like atherosclerosis, Alzheimer’s, and amyloidosis, ApoE plays pivotal roles in plaque formation and fibril assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/23411427/">Additionally, I learnt that it is also detected in fibrillary glomerulonephritis, immunotactoid glomerulonephritis, and monoclonal Ig deposition disease, potentially acting as a scaffolding protein.</a> While its accumulation is significant in DDD, it's also found in other diseases but in lesser amounts. Staining for ApoE aids in diagnosing DDD alongside proliferative glomerulonephritis and bright C3 staining. Kidney accumulation of ApoE occurs predominantly in lipoprotein glomerulopathy and ApoE-related glomerulopathies. ApoE interacts with complement factors, inhibiting inflammation and <a href="https://pubmed.ncbi.nlm.nih.gov/30692699/">regulating complement pathways.</a> Moreover, it's a component of age-related macular degeneration but hasn't been previously identified in DDD dense deposits. This study suggests ApoE binds to heparan sulfate in the glomerular basement membrane, potentially acting as a chaperone for C5-9 proteins, contributing to dense deposit formation. Further investigation is warranted to confirm ApoE's interaction with C5-9 proteins and potential treatment strategies as a result. Kudos to the authors for making this connection. </div>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-21343073315443122792024-02-24T15:05:00.005-05:002024-02-24T15:05:44.440-05:00CONSULT ROUNDS: NELL-1 MEMBRANOUS NEPHROPATHY<p> After PLA2R, NELL-1 related membranous nephropathy(MN) seems to be the second most common MN. Initially, the studies had pointed towards a <a href="https://www.kidney-international.org/article/S0085-2538(20)30956-X/fulltext">cancer-related</a> cause for NELL-1 MN. In recent years and most recently, 2 papers published in 2024 highlight the role of complementary medications. <br /></p><p><a href="https://www.kireports.org/article/S2468-0249(24)01495-5/fulltext">A study from India</a> investigates the clinical outcomes of NELL1-associated MN compared to unidentified antigen-associated MN. Among 46 NELL1 and 36 unidentified antigen-associated MN patients, a significant history of complementary and alternative medicine (CAM) use was noted particularly in the NELL1 group. NELL1-associated MN patients showed a lesser need for immunosuppression, attributed partly to CAM intake, with similar remission rates observed in both groups. The study highlights the distinct clinical features of NELL1-associated MN, including its association with CAM, and suggests a potential for spontaneous remission in these patients. Despite limitations like small sample size and short follow-up, findings indicate CAM's role in NELL1-associated MN and underscore the need for further research in this entity. </p><p><br /></p><p><a href="https://www.kireports.org/article/S2468-0249(24)01491-8/fulltext">A study spanning three institutions </a>in the USA reviewed NELL1 associated MN cases, revealing that 53% of the 70 patients were male, with a median age of 66 and proteinuria of 5.9 grams/day. Associations included lipoic acid (36%), heavy NSAID use (27%), autoimmune diseases (23%), and malignancy (33%). At a median 11-month follow-up, 72% achieved remission, notably 91% in lipoic acid-associated cases with ≥6 months follow-up. Primary NELL1 MN and greater tubular atrophy and interstitial fibrosis predicted lower remission rates, while lipoic acid use correlated with higher complete remission rates, suggesting its discontinuation as a primary treatment strategy.</p><p><br /></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEieNrj0t4MT0mAqwf3othHyAkn9PAY4TnbVmDXWnlDeb0ajHIIpWYWhilEqihE_D5IgjBNgL8I0w9zz64heEmjatTETYdcDSq0dWywjuutgDetVQXNeKUV_VAIWkoFVsEy-_X1kFVJQ7i7RNGq9Mx_5dSKNjzscyoK_RU1YV-brfGgDEWeHkjQwst_peAA" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="886" data-original-width="1575" height="225" src="https://blogger.googleusercontent.com/img/a/AVvXsEieNrj0t4MT0mAqwf3othHyAkn9PAY4TnbVmDXWnlDeb0ajHIIpWYWhilEqihE_D5IgjBNgL8I0w9zz64heEmjatTETYdcDSq0dWywjuutgDetVQXNeKUV_VAIWkoFVsEy-_X1kFVJQ7i7RNGq9Mx_5dSKNjzscyoK_RU1YV-brfGgDEWeHkjQwst_peAA=w400-h225" width="400" /></a></div><br /><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p>I have revised my concept map for NELL-1 MN based on this study to really highlight the CAM and Lipoic acid components. ( created using bio-render).</p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEjiVu9yDNf37_wByxEDhW4Y3WiT9xKktZRwoqkkswnoTWFk94R1ZU7nyDgdhZc4k8F3CzFLCopHVpRlmBcEepSPqdIEIqXZ4fz0pA6AMtiE5RDJA63zuaiKVfdJ6PcbWbftYBhfIXFEcevSk5KaS-8ffJha3U21VPw2ZNYZy4FIL5Xn52njfC5HF5_AHIg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/a/AVvXsEjiVu9yDNf37_wByxEDhW4Y3WiT9xKktZRwoqkkswnoTWFk94R1ZU7nyDgdhZc4k8F3CzFLCopHVpRlmBcEepSPqdIEIqXZ4fz0pA6AMtiE5RDJA63zuaiKVfdJ6PcbWbftYBhfIXFEcevSk5KaS-8ffJha3U21VPw2ZNYZy4FIL5Xn52njfC5HF5_AHIg=w400-h280" width="400" /></a></div><p><br /></p><p><br /></p><p><br /></p><br /><br /><p></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com1tag:blogger.com,1999:blog-5872673930112727345.post-36610580379935401302024-01-27T16:36:00.000-05:002024-01-27T16:36:07.108-05:00Consult Rounds: Hypophosphatemia and Tumor Genesis Syndrome<p>What is this entity? Tumor Genesis Syndrome compared to Tumor Lysis Syndrome.</p><p>Tumor lysis syndrome (TLS) is a critical medical condition that can arise in leukemias and lymphomas either as an initial presentation or after the initiation of anti-neoplastic treatments. Conversely, tumor genesis syndrome (TGS) is a rare occurrence associated with specific malignancies, particularly those characterized by a high neoplastic burden with rapid proliferation, resulting in the excessive uptake of phosphorus from the serum and leading to hypophosphatemia. Interestingly, a subset of patients may experience a combination of TLS and TGS concurrently, resulting in hypophosphatemia instead of the hyperphosphatemia typically seen in TLS.</p><p>From a nephrology perspective, this presents a potential differential diagnosis in leukemic patients. Differentiating hypophosphatemia from TGS is crucial, especially when considering other causes of severe hypophosphatemia related to neoplasms, such as tumor-induced osteomalacia. In this scenario, increased fibroblast growth factor-23 production leads to renal phosphate wasting, mimicking the hypophosphatemia seen in TGS.</p><p>In their literature review, <a href="https://link.springer.com/article/10.1007/s00431-017-2899-7">Chan et al.</a> highlighted an uncommon presentation involving severe hypophosphatemia, hypokalemia, acute renal failure, and acute respiratory failure in a 16-year-old patient with acute leukemia and significant leukocytosis. Conversely, <a href="https://pubmed.ncbi.nlm.nih.gov/29279597/">Zakaria et al.</a> reported a case of a 14-year-old boy with acute T-cell lymphoblastic leukemia who exhibited normal serum biochemistry except for marked hypophosphatemia and elevated LDH levels. Intriguingly, the child showed no symptoms related to low phosphate levels. Additionally, <a href="https://www.kidney-international.org/article/S0085-2538(20)30105-8/fulltext">Radi </a>and Nessim described a case of severe hypophosphatemia in an 82-year-old patient with lymphoma, attributing the cause to neoplastic intracellular phosphate uptake. Similarly, <a href="https://karger.com/aha/article-abstract/64/2/117/27495/Life-Threatening-Hypophosphatemia-in-a-Patient?redirectedFrom=fulltext">Aderka et al. </a>presented a case of a 49-year-old patient with acute myelogenous leukemia experiencing hypokalemia, hypocalcemia, and severe hypophosphatemia (<1 mg/dL) leading to extreme weakness. The hypophosphatemia developed post-chemotherapy initiation and blast lysis, mainly due to the excessive phosphate uptake by leukemic blasts. Recently, <a href="https://www.cureus.com/articles/155649-tumor-genesis-syndrome-presenting-as-severe-hypophosphatemia-in-a-patient-with-t-cell-acute-lymphoblastic-leukemia#!/">another case</a> was described with normal potassium and calcium levels, and despite very low phosphate levels, the patient did not show signs of acute respiratory failure. Additionally, low glucose, elevated LDH, and in some cases elevated lactate may be noted, which may or may not be directly related to TGS but could be a separate effect of leukemia.</p><p>Tumor Genesis Syndrome is a rare syndrome that needs to be considered in the differential diagnosis of hypophosphatemia. </p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-74860889634256759122023-12-27T09:10:00.001-05:002023-12-27T09:10:00.243-05:00Nephro- hospitalists?- should we consider this<p>Not much has been written regarding the role of a nephro-hospitalists in the Nephrology literature. <a href="https://journals.lww.com/cjasn/fulltext/2019/09000/role_of_the_nephro_hospitalist.23.aspx">There is one perspective back in 2019</a>, before the pandemic that discusses the evolution of nephrology as a medical specialty and addresses the challenges it faces, particularly the declining interest among medical trainees in pursuing careers in nephrology. The authors emphasize the importance of adapting to these challenges and propose a solution in the form of a nephrology hospitalist model.</p><p>The field of nephrology has evolved significantly from its early focus on kidney physiology to becoming an independent clinical specialty, particularly with the introduction of dialysis in the 1960s. While patient care was initially delivered primarily in hospitals, the growing population of individuals with kidney disease led to a shift in care to outpatient settings, with a recent emphasis on subspecialized training in transplantation, interventional, and critical care nephrology.</p><p>The decline in interest among medical trainees in nephrology careers is attributed to various factors, including a lack of mentorship, the complexity of kidney physiology, busy workloads, perceived lower compensation, and a perceived lack of innovation in therapies and dialysis.</p><p>To address these challenges, the authors introduce the concept of a nephro-hospitalist model, exemplified by the experience at Washington University in St. Louis. The model involves a dedicated nephrology hospitalist service comprising attending physicians focusing on inpatient care and medical education. Medical students and rotating internal medicine residents are preferentially placed on this service, and the model includes a flexible schedule of alternating periods of service.</p><p>The benefits of this model include improved teaching and mentorship for trainees, increased elective time for fellows, and the opportunity for attending physicians to foster specific interests. The authors highlight the positive impact on education and mentorship, which is crucial for attracting trainees to nephrology.</p><p>However, the authors also acknowledge the downsides to the model, including the need for an every-other-month schedule to prevent burnout and potential limitations in attracting new trainees. Financially, the model is described as roughly break-even, and the authors note that financial considerations should be weighed against the educational benefits.</p><p>The paper discusses other institutions that have adopted similar models with varying success and mentions the potential role of nephrology hospitalists in private practices, particularly to mitigate issues related to "windshield time" and electronic health record systems.</p><p>What have other fields done</p><p>Check out this regarding the role of <a href="https://www.the-hospitalist.org/hospitalist/article/35660/patient-care/onco-hospitalists-bring-value-to-patient-care/">onco-hospitalists</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108059">cancer hospitals</a>.<br />Other fields such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132627/">GI </a>and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726102/">Neurology </a>as well have adopted this model. </p><p>It is possible that a full-time hospital-based nephrology model can be a valuable addition to nephrology education, providing increased attending contact and mentorship for residents and medical students. We should consider further exploration of innovative models to expose trainees to the unique aspects and satisfactions of nephrology, ultimately aiming to address workforce challenges and recruit future nephrologists.</p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-429083776270620042023-12-26T09:04:00.001-05:002023-12-26T09:04:00.141-05:00CMML and the Kidney<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiUxjIse7luhel5KlQfXNfSHkAn-Mun38rnhB4nccyAhTdkuzyvx2LES3wi2loOvybsi5xSvES_Ji-YWfn1p6V20t_-DvpkE299pnOmnsG8VfwDHDvlnEdMB-aikY8RmAtAgtItApbLCzZhtq6xURhAQS4kxrTWtOPgXhRNmpRdD9q8K1PmVh8dFGdLOHg/s564/CMML_kidney_KM.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="274" data-original-width="564" height="194" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiUxjIse7luhel5KlQfXNfSHkAn-Mun38rnhB4nccyAhTdkuzyvx2LES3wi2loOvybsi5xSvES_Ji-YWfn1p6V20t_-DvpkE299pnOmnsG8VfwDHDvlnEdMB-aikY8RmAtAgtItApbLCzZhtq6xURhAQS4kxrTWtOPgXhRNmpRdD9q8K1PmVh8dFGdLOHg/w400-h194/CMML_kidney_KM.jpg" width="400" /></a></div><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p>This figure summarizes the various glomerular, reno-vascular and tubulointerstital disorders seen with Chronic Myelomonocytic leukelmia ( recent r<a href="https://www.kidneymedicinejournal.org/article/S2590-0595(23)00187-5/fulltext#">eview in Kidney Medicine</a> by us)</p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-85977158813428613032023-12-09T11:57:00.007-05:002023-12-09T11:57:58.024-05:00Detective Nephron: Next Venture <p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEj22IphcHYRS0jhI83QmiH8v4nQgvOU6ur1SsXAYzSylHJ4NHWWMWqJNGQq7HJmHvChRdYnzb3BFcxvuxyu12XxHl5dWWu6cjVQvyCpvd2k1h-o9kLpkMAcx_VMbSkHQtTGCUO2LicSRM2yT5Imnw6x14zFxs-UgQ0SThVpaFyYf8yAAdiwLgY1a1HFwI8" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="214" data-original-width="236" height="240" src="https://blogger.googleusercontent.com/img/a/AVvXsEj22IphcHYRS0jhI83QmiH8v4nQgvOU6ur1SsXAYzSylHJ4NHWWMWqJNGQq7HJmHvChRdYnzb3BFcxvuxyu12XxHl5dWWu6cjVQvyCpvd2k1h-o9kLpkMAcx_VMbSkHQtTGCUO2LicSRM2yT5Imnw6x14zFxs-UgQ0SThVpaFyYf8yAAdiwLgY1a1HFwI8" width="265" /></a></div><br /><a href="https://www.kidneynews.org/view/journals/kidney-news/15/12/article-p20_12.xml ">Here is the next venture with a new cast- Graft Guardian</a><p></p><p><br /></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-25523628219798445982023-10-31T06:43:00.006-04:002023-10-31T06:43:51.446-04:00Topic Discussion: Hyponatremia with Spironolactone<p><span style="font-family: arial;">Hyponatremia from MRAs is a rare
phenomenon but we have encountered it clinically. There are times, when we
check labs after starting spironolactone for HTN, 3-4 weeks later, the Potassium
is slightly up and the Na comes back 130 or 131 mmol/L. What is the data and the mechanism for
hyponatremia following spironolactone use? Is this even related.</span></p>
<p class="MsoNormal"><span style="line-height: 107%;"><span style="font-family: arial;"><a href="https://www.ahajournals.org/doi/10.1161/hyp.74.suppl_1.P174">In an
abstract presented at AHA few years ago, small amount of patients were noted in
an EHR to have hyponatremia following starting of spironolactone but most were
following on after being started on a thiazide.</a> <o:p></o:p></span></span></p>
<p class="MsoNormal"><span style="font-family: arial;"><span style="line-height: 107%;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397681/">In another paper,</a>
<span style="background: white; color: #212121;">high doses of furosemide and
spironolactone, or concomitant use of these diuretics, seem to be an important
cause of hyponatremia in HF patients, particularly in combination with advanced
age, diabetes, and alcohol consumption. Diuretic dose reduction may help avoid
hyponatremia and improve clinical status and prognosis in such patients.</span></span>
<o:p></o:p></span></p>
<p class="MsoNormal"><span style="line-height: 107%;"><span style="font-family: arial;">Is it possible that <span style="background: white; color: #222222;">a combination of a thiazide and a K</span><sup style="-webkit-text-stroke-width: 0px; bottom: 0.33em; box-sizing: border-box; font-variant-caps: normal; font-variant-ligatures: normal; max-height: 1e+06px; orphans: 2; text-decoration-color: initial; text-decoration-style: initial; text-decoration-thickness: initial; widows: 2; word-spacing: 0px;">+</sup><span style="-webkit-text-stroke-width: 0px; float: none; font-variant-caps: normal; font-variant-ligatures: normal; orphans: 2; text-decoration-color: initial; text-decoration-style: initial; text-decoration-thickness: initial; widows: 2; word-spacing: 0px;">-sparing diuretic such as amiloride and
spironolactone can increase the risk of hyponatremia because of the enhanced
urinary loss of sodium in the cortical distal tubule? Perhaps not the main
mechanism.<o:p></o:p></span></span></span></p>
<p class="MsoNormal"><span style="font-family: arial;"><span style="background: white; color: #222222; line-height: 107%;">What
about the concept of <a href="https://www.mdpi.com/2227-9059/11/7/1844">vasopressin
escape</a>? During hyponatremia, </span><span style="background: white; color: #212121;">the body limits the degree to which serum
sodium concentration falls through a mechanism called "vasopressin
escape". <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508009/">Vasopressin
escape</a> is a process that prevents the continuous decrease in serum sodium
concentration even under conditions of sustained high plasma vasopressin
levels. In a recent basic science study, the abilities of aldosterone synthase
(Cyp11b2) knockout and wild-type mice to escape from vasopressin were compared.
Wild-type mice escaped while the aldosterone synthase knockout mice did not.
Both the water channel aquaporin 2 (AQP2) and the urea transporter UT-A1
protein abundances were higher in aldosterone synthase knockout than in
wild-type mice at the end of the escape period.<i><b> Vasopressin escape was also
blunted in rats given spironolactone, a mineralocorticoid receptor blocker</b></i>. The
authors results indicate that aldosterone regulates vasopressin escape through
calcineurin-mediated protein changes in UT-A1 and AQP2.</span> <o:p></o:p></span></p>
<p class="MsoNormal"><span style="background: white; color: #212121;"><span style="font-family: arial;"><span> </span>So is it possible that we are blunting the natural
vasopressin escape when we combine thiazides with MRAs? Do all MRAs do this?-
this is still unclear. Hyponatremia related to MRAs is an understudied area
worth exploring. </span></span><span style="background: white; color: #222222; font-size: 12.0pt; line-height: 107%; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-90556929084890944812023-09-23T14:20:00.001-04:002023-09-23T14:20:18.297-04:00Concept Map: AKI in ECMO<p> <table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left; margin-right: 1em; text-align: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7WrRYTA2AB3E_pY9c1XCjf3pG5cVC9SzCzFxsvY9j5RmSVSRS-GL6Svw2xsqc06bLDmrZ_wWaSCwYwrU_4hjZ9GbiMrpumuruXjCIQ6FIuvP8zxhbXF9HLwHhdkRLa_HfRZeqkURKkYIsjkHxt8a0ZRm6FIbQGYvQ-dN4dUOdoG0gFipgibuuP8LYcEs/s3000/Untitled.jpeg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7WrRYTA2AB3E_pY9c1XCjf3pG5cVC9SzCzFxsvY9j5RmSVSRS-GL6Svw2xsqc06bLDmrZ_wWaSCwYwrU_4hjZ9GbiMrpumuruXjCIQ6FIuvP8zxhbXF9HLwHhdkRLa_HfRZeqkURKkYIsjkHxt8a0ZRm6FIbQGYvQ-dN4dUOdoG0gFipgibuuP8LYcEs/w400-h280/Untitled.jpeg" width="400" /></a><br /><br /><br /></td></tr><tr><td class="tr-caption" style="text-align: center;">Concept Map of pathophysiology related to AKI in a patient on ECMO- created by Dr. Purva Sharma using biorender.com </td></tr></tbody></table><br /></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-51880060311776068732023-09-23T07:20:00.001-04:002023-09-23T07:20:12.540-04:00Consult Rounds: BK in non renal solid organ transplantation<p><span style="font-family: arial;"><i><b>What is the incidence of BK viremia, and BK Nephropathy in non renal solid organ transplants?</b></i><br /></span></p><p><span style="font-family: arial;">Not much that I could find in the literature.</span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEgxBrjICTx4PtC21OQonZEeewegp4DzzQ2l_rUWhDaL_41a7nG-pIIh77XOTGhXNEzIl5rftGc698iGIrv070flpr_mSO-9JKqUM9BDjV_gphcOyOZsennouKMxbrR6xjx8oPUc_2C-WjoxmafxrkXBqgvX9Xerk80Pvom31fpl0XJePTraEOU0p1zSqpA" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="554" data-original-width="1361" height="130" src="https://blogger.googleusercontent.com/img/a/AVvXsEgxBrjICTx4PtC21OQonZEeewegp4DzzQ2l_rUWhDaL_41a7nG-pIIh77XOTGhXNEzIl5rftGc698iGIrv070flpr_mSO-9JKqUM9BDjV_gphcOyOZsennouKMxbrR6xjx8oPUc_2C-WjoxmafxrkXBqgvX9Xerk80Pvom31fpl0XJePTraEOU0p1zSqpA" width="320" /></a></span></div><span style="font-family: arial;"><br /><br /></span><p></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;">In this <a href="https://onlinelibrary.wiley.com/doi/10.1111/ctr.14265">retrospective study from 2021</a>, the authors investigated the clinical characteristics, pathological findings, and outcomes of BK viremia and nephropathy in non-renal solid organ transplant patients (NRSOT) who sought nephrology consultation over a five-year period. Among liver, heart, and lung transplant recipients referred to Nephrology, 14% were diagnosed with BK viremia, with a median peak serum BK viral load of 35,500 copies/ml (ranging from 250 to 21,100,000 copies/ml). Notably, BK viremia resolved in six out of seventeen patients (35%), but four out of five biopsied patients exhibited BK virus (BKV) nephropathy. Furthermore, eleven out of the seventeen patients with BK viremia progressed to advanced stages (stage 4 or 5) of chronic kidney disease. Additionally, four patients experienced rejection of their solid organ transplant within the first year following the detection of BK viremia after reducing immunosuppressive treatments. This may be a sign of just net immunosuppression.</span></p><p><span style="font-family: arial;">Another s<a href="https://pubmed.ncbi.nlm.nih.gov/30907978/">tudy back in 2019</a> had looked at literature systematically on report of BK disease in native kidneys. In their review at that time, in heart transplant recipients, 13 cases of BKV nephropathy had been reported, with most occurring in males (10 out of 13), and the mean age being 36.6 years. In lung transplant patients, six cases of BKV nephropathy were identified, with a mean diagnosis age of 47.3 years. Only one case of BKV nephropathy was reported in a liver transplant recipient, and one in a pancreas transplant recipient. More have been reported since their report. The average time from transplant to BKV nephropathy diagnosis in the solid organ transplant population was 2.88 years. For patients who had undergone hematopoietic cell transplantation (HSCT), 19 cases of BKV nephropathy were found, with a mean diagnosis age of 30.6 years. In cases with demographic information, 58% were males, and half of these patients required renal replacement therapy, with a mortality rate of 63.2%. Ten cases of BKV nephropathy were reported in the context of hematologic malignancies, with an average time from malignancy diagnosis to BKV nephropathy diagnosis of 3.06 years. Ten cases of BKV nephropathy were reported in HIV-infected patients, all in males, with a mean age of 34.5 years. Three of these patients required renal replacement therapy, and mortality at the time of publication was 30%. Additionally, individual cases of BKV nephropathy were described in various other clinical settings, such as rheumatoid arthritis, Hyper IgM immunodeficiency syndrome, pulmonary tuberculosis, diabetes mellitus, prostate cancer, and an immunocompromised patient with an unclear medical history. This is fascinating to note that this entity has been ignored in the recent non renal transplant literature. </span></p><p><span style="font-family: arial;">In <span style="background-color: white;">a meta-analysis evaluating the frequency and risk factors for BK viruria and viremia in NRSOT patients, <a href="https://linkinghub.elsevier.com/retrieve/pii/S0955470X15000087">Viswesh et al found</a> a relatively high rate of viruria (8%-52%) but infrequent progression to viremia (3%-7%) and BKV nephropathy (1 biopsy-proven case in an heart transplant recipient).</span><span style="background-color: white;"> </span><span style="background-color: white;">Among those NRSOT patients who did have progression to viremia and BKV nephropathy, heart transplants patients represented the majority of cases. </span><span style="background-color: white;">This finding might be due to the proposed “double-hit” hypothesis, which suggests that the cumulative insult of immunosuppression and renal hypoperfusion secondary to cardiac allograft dysfunction causes clinical progression to BKV nephropathy. </span><span style="background-color: white;"> </span></span></p><p><span style="font-family: arial;">Should implementing a systematic BK screening program could effectively identify and manage this issue in the NRSOT population and or HCT patients?</span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-69553106762543855482023-08-25T06:03:00.001-04:002023-08-25T06:03:00.265-04:00In the News: Is it prime for Xenotransplantation<p>A seminal paper in <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01349-1/fulltext">Lancet published in 2023</a> focuses on the immune response after pig-to-human kidney xenotransplantation. The study uses a comprehensive approach to characterize this response in detail. </p><p>Two pig kidney xenografts transplanted into deceased human recipients were thoroughly analyzed using various methods including morphological evaluation, immunophenotyping, gene expression profiling, digital spatial profiling, and cell deconvolution. The findings indicate early signs of antibody-mediated rejection, with evidence of microvascular inflammation, immune deposits, endothelial cell activation, and positive xeno-reactive crossmatches. The inflammation primarily consists of innate immune cells like CD68+, CD15+, and NKp46+ cells. Gene expression analysis reveals increased activation of various immune-related pathways, such as monocyte and macrophage activation, natural killer cell response, endothelial activation, complement activation, and T-cell development. </p><p>The injury associated with antibody-mediated rejection is concentrated in the glomeruli of the xenografts, with transcripts related to monocytes, macrophages, neutrophils, and natural killer cells being significantly enriched. This rejection pattern is distinct from control autografts and ischemia-reperfusion models. The study suggests that despite initial positive outcomes, antibody-mediated rejection might still be occurring in pig-to-human kidney xenografts. The findings highlight potential therapeutic targets to address the humoral aspect of rejection and improve the success of xenotransplantation.</p><p>Interestingly, <a href="https://jamanetwork.com/journals/jamasurgery/fullarticle/2808483">in JAMA surgery, a case report</a> is published at the same time. The paper presents a case involving a male individual in his 50s who was declared brain dead and had acute kidney injury on top of a history of chronic kidney disease (CKD) and hypertension. After all other organ donation options were exhausted, the individual received bilateral native nephrectomy and cessation of dialysis. Crossmatch-compatible xenotransplantation was performed using 10-gene-edited pig kidneys (UKidney). The pig kidneys were modified with 10 gene changes, including knockdowns, knockouts, and human transgene insertions. The recipient was treated with a complement inhibitor (anti-C5; eculizumab) prior to xenotransplantation, followed by standard induction therapy and maintenance immunosuppression. The pig kidneys were transplanted en bloc with their vasculature anastomosed to the recipient's arteries and veins, and the ureters connected to the recipient's bladder. The pig kidneys exhibited rapid function, producing significant amounts of urine within minutes of reperfusion, and urine concentration improved over time. Serum creatinine levels dropped significantly after xenotransplantation, and creatinine clearance improved as well.</p><p>Biopsies of the xenografts showed normal histology without evidence of thrombotic microangiopathy. The authors discuss that while this case series demonstrates the success of pig-to-human xenotransplantation in providing kidney function to a deceased individual with CKD, more research with living human recipients is needed to determine the long-term function of xenograft kidneys and their potential use as a solution for the organ shortage crisis. Although single case, it highlights the potential of xenotransplantation as a viable solution for addressing the shortage of organs, which results in preventable deaths annually.</p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-51000331558942343752023-08-24T05:57:00.006-04:002023-08-24T05:57:56.334-04:00In the News: Urine Na as a marker for diuresis success<p><a href="https://www.ahajournals.org/doi/10.1161/JAHA.123.030044">A recent editorial in JAHA </a>discusses the use of urinary sodium (UNa) as a biomarker for monitoring and guiding diuretic therapy in patients with acute heart failure (AHF). Activation of the renin-angiotensin system in heart failure leads to sodium retention, hyperaldosteronism, and increased sympathetic activity, contributing to fluid overload. The authors highlight that assessing diuretic response through traditional methods, such as weight loss and urine volume output, can be inaccurate and logistically challenging. Instead, they propose using <b>UNa measurements </b>from spot urine samples taken 2 hours after diuretic administration as a more dynamic and early indicator of diuretic response.</p><p><a href="https://pubmed.ncbi.nlm.nih.gov/34447992/">The European Society of Cardiology (ESC)</a> guidelines recommend using spot UNa analysis to evaluate diuretic treatment response in AHF patients. A low UNa (<50-70 mEq/L) at 2 hours post-diuretic administration is associated with inadequate diuretic response and suggests the need for more intensive diuretic therapy. The paper discusses observational studies and expert opinions that support this approach. However, it also points out limitations, such as the influence of kidney function, concurrent conditions like chronic kidney disease (CKD) and cirrhosis, and the potential loss of UNa's predictive strength after the first day of treatment due to changes in sodium excretion patterns.</p><p>The authors present data from studies that endorse the feasibility and efficacy of UNa-guided diuretic therapy in AHF. They discuss the <a href="https://pubmed.ncbi.nlm.nih.gov/34708555/">ENACT HF trial,</a> which showed improved natriuresis, diuresis, and shorter hospitalization duration with UNa-guided diuretic treatment. Another ongoing study, PUSH-AHF, aims to provide more definitive results on natriuresis-guided therapy using a stepwise diuretic approach.</p><p>The authors acknowledge that UNa assessment alone may not fully capture diuretic response and recommend combining UNa measurements with other indicators of decongestion, such as urine output. They also emphasize the importance of accounting for different patient factors like fluid overload status, kidney function, and the type of diuretics used.</p><p>In conclusion, while UNa-guided diuretic therapy appears promising for AHF management.. interesting and simple to do.</p><p>Love this figure from the paper</p><p><br /></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEi-l4-bOALajRZtoW2iJLBuY7RuFqB8C92aMZMKZIt39Tf0TnX-h0TJdZzBUnIAhMEWMUi2y6YTd_rTPNo4fEqGQhOY5HHoEOKbcqx7h5Vsqe0nlpUIjW5MwKxnaJhwtWq7FuHwRbTA93FKcwG3hY2lTXRG3--UoqF15LcLIWdBoeEijAYPC-1xMvsb_jk" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="840" data-original-width="2128" height="158" src="https://blogger.googleusercontent.com/img/a/AVvXsEi-l4-bOALajRZtoW2iJLBuY7RuFqB8C92aMZMKZIt39Tf0TnX-h0TJdZzBUnIAhMEWMUi2y6YTd_rTPNo4fEqGQhOY5HHoEOKbcqx7h5Vsqe0nlpUIjW5MwKxnaJhwtWq7FuHwRbTA93FKcwG3hY2lTXRG3--UoqF15LcLIWdBoeEijAYPC-1xMvsb_jk=w400-h158" width="400" /></a></div><br /><br /><p></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-1791543869846914812023-07-20T06:21:00.002-04:002023-07-20T06:21:26.522-04:00In the NEWs- New Myeloma Working Group Update-- Myeloma related renal disease management<p> An important guideline/recommendation was published in<a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00223-1/fulltext"> Lancet thismonth</a>. This is an evidence based summary by the International Myeloma Working
Group on myeloma related kidney disease. A must read!</p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><i>Here is a summary of the findings</i><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">1.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Diagnosis is important- the serum free light
chain becomes the corner stone of diagnosis. An algorithm below summarizes the
novel way of looking at it. <span style="color: #221e1f;">All patients with
multiple myeloma and renal impairment should have serum creatinine, estimated
glomerular filtration rate, and FLCs measurements together with 24-h urine
total protein, electrophoresis, and immunofixation. If non-selective
proteinuria (mainly albuminuria) or involved serum FLCs value less than 500
mg/L is detected, then a renal biopsy is needed.</span><o:p></o:p></span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="color: #221e1f;"></span></span></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEhwse6BQY_E2MiOxvjxfSGeZ1icYbxUPkTcuWZzNepwuxsEnhgaYUp0cKV6WsYLOnMH_7nQWxD8h0epamzWB1hjhfoc7RbzEMz2VazcXlyNxBhhP2lGlRa1RGkiWrKZ6Kny7pYXVYAqc2hXY6_40UZkOv31RAAQe6tctYhs_XCcGDxg1XiHe14Fk71mn80" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="472" data-original-width="940" height="201" src="https://blogger.googleusercontent.com/img/a/AVvXsEhwse6BQY_E2MiOxvjxfSGeZ1icYbxUPkTcuWZzNepwuxsEnhgaYUp0cKV6WsYLOnMH_7nQWxD8h0epamzWB1hjhfoc7RbzEMz2VazcXlyNxBhhP2lGlRa1RGkiWrKZ6Kny7pYXVYAqc2hXY6_40UZkOv31RAAQe6tctYhs_XCcGDxg1XiHe14Fk71mn80=w400-h201" width="400" /></a></div><br /><br /><p></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><br /></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><br /></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><br /></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">2.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">How high is the involved FLC—can tell you if
this is cast nephropathy vs looking for a glomerular process. In addition – the
urine protein being selective vs non selective can aid in overflow proteinuria
vs a true glomerular process.<o:p></o:p></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-list: Ignore;">3.<span style="font: 7.0pt "Times New Roman";">
</span></span><!--[endif]-->Kidney biopsy is NOT required but may be
recommended if suspicious of cast nephropathy is high. <a href="https://ashpublications.org/blood/article/135/21/1833/452677/Clinicopathologic-predictors-of-renal-outcomes-in">Although recent studieshave shown that the IFTA and number of casts presents on renal bx can predictrenal outcomes.</a><o:p></o:p></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">4.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">The IMWG criteria for renal response was
recommended( change in eGFR)- see table below. This is used for many studies
and validated. <o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"></span></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEjJhcWmselh8hcZBQyhy8KRANwR66OOEF2GlGtRrheEwtRqlWiw5hY3lwrU7yM_azurLS0xNA6wC6nnohrW7At9Bd8ZmwaVX3Fanc9kaYt1Lx_lEKE9RDAUFs5OLOMOmknTgT8Jo-7NIpOxBWA8VyGrl6KyOg6hfOY72SlsYiAtp_3ONz4_mInCN6hKRCE" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="312" data-original-width="534" height="187" src="https://blogger.googleusercontent.com/img/a/AVvXsEjJhcWmselh8hcZBQyhy8KRANwR66OOEF2GlGtRrheEwtRqlWiw5hY3lwrU7yM_azurLS0xNA6wC6nnohrW7At9Bd8ZmwaVX3Fanc9kaYt1Lx_lEKE9RDAUFs5OLOMOmknTgT8Jo-7NIpOxBWA8VyGrl6KyOg6hfOY72SlsYiAtp_3ONz4_mInCN6hKRCE" width="320" /></a></div><br /><br /><p></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><br /></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><br /></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><br /></span></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">5.<span style="font: 7.0pt "Times New Roman";"> </span></span></span><span style="text-indent: -0.25in;"><span style="font-feature-settings: normal; font-kerning: auto; font-optical-sizing: auto; font-size: 7pt; font-stretch: normal; font-variant-alternates: normal; font-variant-east-asian: normal; font-variant-numeric: normal; font-variation-settings: normal; line-height: normal;"> </span></span><span style="color: #221e1f; text-indent: -0.25in;">Supportive care and high-dose
dexamethasone are required for all patients with myeloma-induced renal
impairment( fluids, correction of hypercalcemia, avoiding NSAIDS)</span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">6.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="color: #221e1f; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Mechanical approaches do not
increase overall survival( plasma exchange- data is in the non bortezomib era,
and HCO dialyzer- two RCTs showed no benefit). </span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">7.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="color: #221e1f; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Bortezomib-based regimens are
the cornerstone of the management of patients with multiple myeloma and renal
impairment at diagnosis. New quadruplet and triplet combinations, including
proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal
antibodies, improve renal and survival outcomes in both newly diagnosed
patients and those with relapsed or refractory disease. The panel suggested to </span><span style="color: #0f1419; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Start
Daratumumab + Bortezomib + Dex early and then add IMiD starting cycle two once renal
function has stabilized.</span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">8.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="color: #0f1419; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Carfilzomib should not be first
line in patients with CKD as risk of TMA( first time someone mentioning this)-
glad the toxicities are being considered.. But then again- is the incidence of
TMA from carfilzomib that high- I don’t think so.</span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">9.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="color: #0f1419; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Dose adjustments are discussed
for all anti Myeloma agents and their potential nephrotoxicities- mainly the
TMA from carfilzomib. There are other renal toxicities of other agents as well
not mentioned here.</span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;">10.<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span style="mso-spacerun: yes;"> </span><span style="color: #221e1f;">Conjugated antibodies, chimeric antigen receptor T-cells,
and T-cell engagers are well tolerated and effective in patients with moderate
renal impairment</span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p>
<p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -.25in;"><!--[if !supportLists]--><span style="mso-list: Ignore;">11.<span style="font: 7.0pt "Times New Roman";">
</span></span><!--[endif]--><span style="color: #0f1419; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Finally, with improved survival
in myeloma, when should we consider kidney transplantation in pts. with ESKD?
Should we use sustained MRD-negativity to select transplant candidates? What
about the MGRS patients?—the consensus was 2 years of disease free state. But low
level evidence.. I have seen sooner in most cases. Overall <a href="https://pubmed.ncbi.nlm.nih.gov/35687020/">their outcomes are not great </a>when compared to non myeloma ESKD. </span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-10590992653134035322023-07-07T06:05:00.005-04:002023-07-07T06:06:30.746-04:00In the NEWS: Biomarkers-- Hype or Hope for AIN<p><span style="font-family: arial;"><a href="https://www.jci.org/articles/view/168950">A new study in JCI sheds light into a potential biomarker for Acute Interstitial Nephritis. This entity has been the bane of Nephrologists' existence. Its a hard diagnosis to make and treatment is the usual- steroids. </a></span></p><p><span style="font-family: arial;">First came the urine eosinophils-- then they were found to be useless. Apparently, despite several studies showing no clear benefit in diagnosing AIN, several folks love to order this useless test. </span></p><p><span style="font-family: arial;">A slew of biomarkers came and went but none were real superhits for AIN. <a href="https://pubmed.ncbi.nlm.nih.gov/31092735/">TNF-alpha and IL-9 were two potential candidates over the last few years</a>. The authors of a recent study published in JCI performed urine proteomics to identify a potential candidate that maybe best and top contender for AIN- chemokine C-X-C motif ligand 9( CXCL9). This was then externally validated and then confirmed in kidney tissue of AIN patients compared to control groups. They also <span style="background-color: white;">showed that urinary CXCL9 together with TNF-α and IL-9 is the optimal combination of biomarkers for AIN diagnosis.</span></span></p><p><span style="font-family: arial;"><span style="background-color: white;">Here is the visual abstract from the paper</span></span></p><p><span style="font-family: arial;"><span style="background-color: white;"><br /></span></span></p><p><span style="font-family: arial;"><span style="background-color: white;"></span></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEg8FcFtCDflrapezF2_8DNSYaEKIW3k3nsKaQMF3J6j7SaGOaPM_QQghe2NBP4sbzMaGpw_UX7EP4aw2UlrMmsZMmrmVsrJLmHyXMtZLF6RIxE6szxihA6UodYZ2HUaXs_SxTkzcDuhXsqdHwAoA24l-pVeC164NEtAULgIalTwyorM0DN6FPrGPtakVn0" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="551" data-original-width="699" height="316" src="https://blogger.googleusercontent.com/img/a/AVvXsEg8FcFtCDflrapezF2_8DNSYaEKIW3k3nsKaQMF3J6j7SaGOaPM_QQghe2NBP4sbzMaGpw_UX7EP4aw2UlrMmsZMmrmVsrJLmHyXMtZLF6RIxE6szxihA6UodYZ2HUaXs_SxTkzcDuhXsqdHwAoA24l-pVeC164NEtAULgIalTwyorM0DN6FPrGPtakVn0=w400-h316" width="400" /></a></span></div><span style="font-family: arial;"><br /><br /></span><p></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;">What is this CXCL-9? Apparently, it is a<span style="background-color: white;"> monokine induced by IFN-γ, is a chemokine that binds to its receptor, CXCR-3, and promotes lymphocyte recruitment at sites of inflammation.</span></span></p><p><span style="background-color: white;"><span style="font-family: arial;">It has been shown to be associated with</span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><br /><a href="https://pubmed.ncbi.nlm.nih.gov/23968332/">acute cellular rejection( makes sense- similar to AIN)</a><br /><a href="https://pubmed.ncbi.nlm.nih.gov/26694099/">predict future risk of rejection</a><br /><a href="https://insight.jci.org/articles/view/165108">AIN associated with immunotherapy ( inviting T cells and monokine)</a><br /><a href="https://pubmed.ncbi.nlm.nih.gov/36693381/">Predicting any immune mediated events when using ICI therapy</a></span></span></p><p><span style="background-color: white;"><span style="font-family: arial;">Drawbacks-- may not tell you specifically what is the cause of the T cell invitation but can clearly tell you a clue. Urinary tests are usually challenging in oligo-anuric AIN. </span></span></p><p><span style="background-color: white;"><span style="font-family: arial;">It seems that the combination of TNF-alpha, CXCL-9 and IL-9 may hold promise for AIN. </span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><a href="https://www.nejm.org/doi/full/10.1056/nejmoa1215555">Despite amazing advances in urinary markers in transplant rejection</a> since last 15 years, we are not using it in clinical practice. </span></span></p><p><span style="background-color: white;"><span style="font-family: arial;">Lets hope that it is the troponin for AIN else we are still doing renal bx to confirm these tough diagnosis. </span></span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-33041312111133055942023-06-04T08:41:00.006-04:002023-06-04T08:46:34.343-04:00Consult rounds: Hyperammonemic encephalopathy in the setting of myeloma<p></p><p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><b>Can paraproteinemia cause an elevated ammonia level?</b><o:p></o:p></span></p>
<p class="MsoNormal">While liver disease and certain medications are known to cause
hyperammonemia, myeloma is a rare cause of hyperammonemia. One of the first
cases published on this topic was back in 2002 in <a href="https://www.nejm.org/doi/full/10.1056/NEJM200205233462119">NEJM.</a></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Here are some cases published in the literature.<o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/</a>
<o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891795/</a><o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://www.amjmed.com/article/S0002-9343(03)00630-2/fulltext">https://www.amjmed.com/article/S0002-9343(03)00630-2/fulltext</a>
<o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-022-01285-6">https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-022-01285-6</a><o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://pubmed.ncbi.nlm.nih.gov/35871579/">https://pubmed.ncbi.nlm.nih.gov/35871579/</a><o:p></o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p> </o:p></span></p>
<p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><a href="https://ashpublications.org/blood/article/120/21/5002/87221/Plasma-Cell-Myeloma-Causing-Hyperammonemia"><span> </span>A
retrospective study shed more light</a>. In this study of<span style="background: white;"><span style="mso-spacerun: yes;"> </span>individual patients
diagnosed with ammonia related disease from myeloma was evaluated( 27
patients), interesting findings were noted. The mean age
was 76 years with a 5:1 male-to-female ratio. All had stage III based on the
International Staging Scale (ISS). Bone marrow biopsies demonstrated 54–98%
(mean 69%) plasma cell infiltration. IgA subtype was the most common. The mean ammonia level was 113
umol/L. No intracranial processes were
detected on imaging. Three patients had improvement in mental status and
decreased ammonia levels after chemotherapy; the other three patients declined
further interventions. Inpatient mortality was over 66%. </span></span></p><p class="MsoNormal"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="background: white;"><span> </span>The authors also did a MEDLINE
search revealing 20 articles originating from the United States and Japan
detailing a total of 32 patients who were diagnosed with myeloma induced
hyperammonemic encephalopathy. The mean age was 52 years with an equal distribution between men and women. The average ammonia level
amongst these patients was 121 umol/L with as high as 299umol/L. All these
patients had stage III disease by the ISS or the Durie-Salmon system. IgG was
the most common subtype at 44% (n=12), followed by IgA with 37% (n=10), light
chain multiple myeloma with 11% (n=3), and IgD with 7% (n=2). Of the 25
patients that received chemotherapy, 15 (60%) survived until discharge. The
inpatient mortality was 40% (n=10). Those patients who did not receive
chemotherapy had a lower rate of survival at 25%.</span></span><o:p></o:p></p>
<p class="MsoNormal"><span style="background: white; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">Some studies report beneficial
effects in using hemodialysis to remove <a href="https://pubmed.ncbi.nlm.nih.gov/23404638/">excess ammonia</a>. Several
others suggest that the initiation of aggressive chemotherapy is the most
effective measure to achieve normal ammonia levels and <a href="https://pubmed.ncbi.nlm.nih.gov/20929329/">clinical improvement</a>. Mechanism of this association is still unclear. <o:p></o:p></span></p>
<p class="MsoNormal"><span style="background: white; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;">It is important to consider myeloma
as a cause of hyperammonemia. </span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><o:p></o:p></span></p><br /><p></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-13327512626866475032023-05-22T19:52:00.004-04:002023-05-22T19:52:00.141-04:00Concept Map- Immune checkpoint inhibitors and AKI- biomarkers <p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpdRJMIj4Efnxk5hIyMgwSM-9BfwVmYndYlRtJ2Tl6KjMM89Sxg7O4PCMzejKnxZ30ZPJj5UzQZ5CPRI_2SaPGlUsF_Os-CqmKPELJ4Wx3SZx9z4v3jVP_XYxuQQCzJF6e6RaNYuJjsuR7ssQGLJJMOKKOemOkrE4EsCtkFXju-ClEoiuqoRFo8f6C/s3000/Biomarkers-AKI-ICI.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpdRJMIj4Efnxk5hIyMgwSM-9BfwVmYndYlRtJ2Tl6KjMM89Sxg7O4PCMzejKnxZ30ZPJj5UzQZ5CPRI_2SaPGlUsF_Os-CqmKPELJ4Wx3SZx9z4v3jVP_XYxuQQCzJF6e6RaNYuJjsuR7ssQGLJJMOKKOemOkrE4EsCtkFXju-ClEoiuqoRFo8f6C/w400-h280/Biomarkers-AKI-ICI.jpg" width="400" /></a></div><br /> <p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p>As of 2023, this is the most updated bio-markers that have been studied at single centers around the world for AKI associated with ICI therapy. </p><p><br /></p><p>References:</p><h1 class="article-title" style="background-color: white; box-sizing: border-box; color: #222222; font-weight: normal; line-height: 1.4; margin: 0.2rem 0px 0.5rem; padding: 0px; text-rendering: optimizelegibility;"><span style="font-family: times; font-size: small;"><a href="Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis">Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis</a></span></h1><div><span style="background-color: white; color: #333333;"><a href="Soluble and cell-based markers of immune checkpoint inhibitor-associated nephritis"><span style="font-family: times;">Soluble and cell-based markers of immune checkpoint inhibitor-associated nephritis</span></a></span></div><div><span style="font-family: times;"><br /></span></div><div><a href="https://jitc.bmj.com/content/9/10/e003467"><span style="font-family: times;">AKI in patients with immune check point inhibitors</span></a></div><div><span style="font-family: times;"><br /></span></div><div><a href="https://www.kireports.org/article/S2468-0249(21)00015-2/fulltext"><span style="font-family: times;">Biomarkers, Clinical Features and rechallenge for ICI related renal immune related adverse events</span></a></div><div><span style="font-family: times;"><br /></span></div><div><a href="https://www.kireports.org/article/S2468-0249(22)01883-6/fulltext"><span style="font-family: times;">Cytokines and immune cell phenotypes in AKI associated with ICI</span></a></div><div><a href="https://www.kireports.org/article/S2468-0249(22)01913-1/fulltext"><span style="font-family: times;"><br /></span></a></div><div><a href="https://www.kireports.org/article/S2468-0249(22)01913-1/fulltext"><span style="font-family: times;">Differentiating acute interstitial nephritis from ICI from other causes</span></a></div><div><br /></div>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-6770692524039295912023-05-03T05:57:00.001-04:002023-05-16T13:02:44.539-04:00Concept Map: Endothelin-1 and the Kidney<p>Emerging concept of use of endothelin antagonists in the field of Nephrology. This concept figure is on data up to May 2023</p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEha5b1xVLEM8Gw_z93Y15CbLJDTiJfTOqMMnK_gabFJQiHNS9tT6ZCqoOC6HRn3XDYNsln-dGkMslWcxd2x9H5rdQIKsjwgePPmrcdLXAj-mJ_eUCr9HZ7oVmtBoeDX9G3Do5no8wCGxaTZ5V8rr1EAWa-JI0RP9ohOqzMYOl4bziZOh3YjiwYcVFyR/s3000/Endothelin-1%20and%20Kidney%20.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEha5b1xVLEM8Gw_z93Y15CbLJDTiJfTOqMMnK_gabFJQiHNS9tT6ZCqoOC6HRn3XDYNsln-dGkMslWcxd2x9H5rdQIKsjwgePPmrcdLXAj-mJ_eUCr9HZ7oVmtBoeDX9G3Do5no8wCGxaTZ5V8rr1EAWa-JI0RP9ohOqzMYOl4bziZOh3YjiwYcVFyR/w400-h280/Endothelin-1%20and%20Kidney%20.jpg" width="400" /></a></div><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p>Figure created using biorender.com and adapted <a href="https://www.mdpi.com/1422-0067/24/4/3427">from this review.</a> </p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-21476941494630866842023-05-02T14:54:00.001-04:002023-05-02T14:54:00.149-04:00Topic Discussion: Mastocytosis and the Kidney<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhrtF__bFRWbhOF3IlrJs7bg3w5EJTmn6U1TOiRB4qk4HUPTRADw5Qb3kAgYdh7ad66yvyvuarxsg7yHnNBXHiubzvCUYfJns1blFwrt7BXCE2ceLqK6A8m0Nv4VdbUlSPvPru6lruBDwDxhKeIz1mHF-yhGfi21XqeIaLgCYwCX_ArbGQ_FmXx_QfZ/s3000/Mastocytosis%20and%20Kidney%20_Figure_revision.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="224" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhrtF__bFRWbhOF3IlrJs7bg3w5EJTmn6U1TOiRB4qk4HUPTRADw5Qb3kAgYdh7ad66yvyvuarxsg7yHnNBXHiubzvCUYfJns1blFwrt7BXCE2ceLqK6A8m0Nv4VdbUlSPvPru6lruBDwDxhKeIz1mHF-yhGfi21XqeIaLgCYwCX_ArbGQ_FmXx_QfZ/s320/Mastocytosis%20and%20Kidney%20_Figure_revision.jpg" width="320" /></a></div><br /><div class="separator" style="clear: both; text-align: center;"><span style="background-color: white;"><span style="font-family: arial;"><br /></span></span></div><p></p><p><span style="background-color: white;"><span style="font-family: arial;">A recent review by us in<a href="https://academic.oup.com/ndt/advance-article-abstract/doi/10.1093/ndt/gfad081/7146207?redirectedFrom=fulltext"> NDT discusses the kidney involvement in systemic mastocytosis.</a></span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><span style="white-space: pre-wrap;">Systemic mastocytosis(SM) is a clonal mast cell disorder due to a somatic gain-of-function mutation in the KIT gene resulting in mast cell accumulation in tissues. </span><span style="white-space: pre-wrap;">SM manifests as symptoms related to mast cell mediator release (flushing, pruritus, cramps, diarrhea, bronchospasm, angioedema) and organ damage. S</span><span style="white-space: pre-wrap;">kin involvement is frequent, esp. in indolent SM, red-brown macules and papules, fine telangiectasias, urticate on stroking </span></span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><span style="white-space: pre-wrap;">Kidney involvement:
1)Paraprotein-related kidney disease like light chain amyloidosis and MIDD, common association between plasma cell dyscrasia and SM
</span><span style="white-space: pre-wrap;">2)Immune-mediated GN like mesangial proliferative GN, membranous GN, and diffuse proliferative GN. Hypothesis- Increased circulating immune complexes and vasodilatory mediators released by mast cells increase glomerular permeability.
</span><span style="white-space: pre-wrap;">3)nephrotoxicity of drugs to treat SM: IFN-alpha, bisphosphonates, tyrosine kinase inhibitors</span></span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">4)nephro-urolithiasis: increased prevalence in SM. Be careful of mast cell mediator release from treatment used for stones. Avoid radiocontrast agents, use pre-operative steroids, use selective COX-2 inhibitors</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">5)bladder mast cell infiltration causing interstitial cystitis</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">Treatment of SM-directed therapy includes agents to control mediator release, and mast cell clone directed therapy, interstitial nephritis is typically treated with glucocorticoids in addition.</span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><span style="white-space: pre-wrap;">Although rare, kidney involvement is increasingly described, </span><span style="white-space: pre-wrap;">either direct or indirect</span></span></span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-43906233944337058142023-04-29T14:53:00.004-04:002023-04-29T14:54:02.094-04:00Topic Discussion: Atypical anti GBM disease<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEgMmPj6XOmCrfep69HnzCvOJx_LCZiMQxSbZ7YbMJ6rigt9vy4ONxTkNj_33nU0nibNM75yxPtvuCIrJrEeT0hKm4720IZNB6eiCWsAvuc2gxmjcOc8oBCtg0AFfI5M1orQ6VSaOHY__xGbEKaJV4jjPPej5ltm9UbTt42zGZGJicB8EUcl4JIyC0yl" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="253" data-original-width="508" height="159" src="https://blogger.googleusercontent.com/img/a/AVvXsEgMmPj6XOmCrfep69HnzCvOJx_LCZiMQxSbZ7YbMJ6rigt9vy4ONxTkNj_33nU0nibNM75yxPtvuCIrJrEeT0hKm4720IZNB6eiCWsAvuc2gxmjcOc8oBCtg0AFfI5M1orQ6VSaOHY__xGbEKaJV4jjPPej5ltm9UbTt42zGZGJicB8EUcl4JIyC0yl" width="320" /></a></div><span style="font-family: arial;">We are aware that c<span style="background-color: rgba(255, 255, 255, 0.03); white-space: pre-wrap;">irculating anti-GBM antibodies are directly pathogenic in anti-GBM disease. However, about 10% of patients with anti-GBM disease do not have circulating anti-
GBM antibodies. </span></span><p></p><p><span style="font-family: arial;"><span style="background-color: rgba(255, 255, 255, 0.03); white-space: pre-wrap;"><br /></span></span></p><p><span style="font-family: arial;"><span style="background-color: rgba(255, 255, 255, 0.03); white-space: pre-wrap;"><br /></span></span></p><p><span style="font-family: arial;"><span style="background-color: rgba(255, 255, 255, 0.03); white-space: pre-wrap;">Atypical anti-GBM disease is considered when patients have linear IgG deposition along the glomerular basement membrane without anti-GBM antibodies in the circulation.</span></span></p><p><span style="background-color: rgba(255, 255, 255, 0.03); font-family: arial; white-space: pre-wrap;">Atypical anti-GBM disease comprises 8% to 12% of all anti-GBM disease cases. About 2% to 8% of patients with anti-GBM disease have negative serology despite rigorous testing.</span></p><p><span style="font-family: arial;"><span style="background-color: rgba(255, 255, 255, 0.03); white-space: pre-wrap;">Pathogenesis: </span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">(1)different composition of antigen/epitope: a)Antibodies against
the NC1 domain of other alpha chains like alpha1, alpha4, or alpha5 chains of type IV
collagen or to the NC1 domain of alpha345 hexamers, b)Linear epitopes of the
collagenous domain, or C)entactin</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">(2)different affinity of antibodies: a) high-affinity autoantibodies
trapped in the kidneys and present with low titer in circulation, or (b)Autoantibodies could also have a low affinity for the substrate in the assay</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;">(3) different types of antibody: a). the dominance of different IgG subclass
such as IgG4 or IgG1 and frequent presence of IgG2, b) presence of IgA or IgM dominance which is not exactly atypical anti-GBM diseases in terms of clinical/pathological presentation</span></span></p><p><span style="background-color: white; font-family: arial; white-space: pre-wrap;">Pathology: (i) Lack diffuse crescentic and </span><span style="background-color: white; font-family: arial; white-space: pre-wrap;">necrotizing glomerulonephritis, (ii). Light microscopy heterogenous: mesangial and/or endocapillary proliferative GN, MPGN, FSGS, mesangial sclerosis; and glomerular endothelial changes resembling TMA are common</span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;"><b>Monotypic atypical anti-GBM disease:</b> Monotypic Ig deposits along the GBM are increasingly observed to cause a disease pattern similar to atypical anti-GBM. Needs further study to confirm if it is a form of MGRS?</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;"><b>Prognosis: </b>Kidney dysfunction is usually milder and evolves slower than classic anti-GBM disease; however, presentation as RPGN has also been reported. Proteinuria and nephrotic syndrome are more frequent than classic anti-GBM disease.</span></span></p><p><span style="background-color: white; white-space: pre-wrap;"><span style="font-family: arial;"><b>Treatment:</b> is individualized and typically consists of immunosuppressive agents used to treat classic anti-GBM disease or monotherapy with renin-angiotensin-aldosterone blockers</span></span></p><p><span style="white-space: pre-wrap;"><span style="color: #0f1419; font-family: arial;"><span style="font-size: 15px;"><a href="https://www.kireports.org/article/S2468-0249%2823%2901228-7/fulltext">Check out this review </a></span></span></span></p><p><span style="white-space: pre-wrap;"><span style="font-family: TwitterChirp, -apple-system, BlinkMacSystemFont, Segoe UI, Roboto, Helvetica, Arial, sans-serif;"><span style="color: #0f1419;"><span style="font-size: 15px;"></span></span></span></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: TwitterChirp, -apple-system, BlinkMacSystemFont, Segoe UI, Roboto, Helvetica, Arial, sans-serif;"><span style="color: #0f1419;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEhxkwKYhDDWZsxpEVPdtIexoDnttDSf-ljHRfabV1bHYTN2BK_Z_93FzhJZyAwRsM6gs4r9dC4Oyo7PjUR1u4XiV-2S-EssckAKW5KSVx7vd0io-puKJ6QMwxM6o_FrMfdVGjZXgNa2bohISBLYzAE-Pvg9nRAtJEQ_Qz3Ree8vSRAEFN9gM8zLseIL" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="1080" data-original-width="1920" height="225" src="https://blogger.googleusercontent.com/img/a/AVvXsEhxkwKYhDDWZsxpEVPdtIexoDnttDSf-ljHRfabV1bHYTN2BK_Z_93FzhJZyAwRsM6gs4r9dC4Oyo7PjUR1u4XiV-2S-EssckAKW5KSVx7vd0io-puKJ6QMwxM6o_FrMfdVGjZXgNa2bohISBLYzAE-Pvg9nRAtJEQ_Qz3Ree8vSRAEFN9gM8zLseIL=w400-h225" width="400" /></a></span></span></div><span style="font-family: TwitterChirp, -apple-system, BlinkMacSystemFont, Segoe UI, Roboto, Helvetica, Arial, sans-serif;"><span style="color: #0f1419;"><br /><br /></span></span><div class="separator" style="clear: both; text-align: center;"><br /></div><br /><p></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-83121120924429020212023-03-10T07:03:00.002-05:002023-03-10T07:23:00.228-05:00Topic Discussion: Calcium and Pre-eclampsia- using AI<p> I now am re-doing the post on using calcium to prevent pre-eclampsia using artificial intelligence website- <a href="https://chat.openai.com/chat">https://chat.openai.com/chat </a></p><p>Prompt: Can calcium prevent PEC?</p><p>Response: </p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 0px 0px 1.25em; white-space: pre-wrap;">Calcium supplementation has been shown to reduce the risk of pre-eclampsia in pregnant women who have low dietary calcium intake or are at high risk for pre-eclampsia. However, it is important to note that calcium supplementation is not a guaranteed prevention method for pre-eclampsia and should only be taken under the guidance of a healthcare professional.</p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px; white-space: pre-wrap;">The World Health Organization (WHO) recommends that pregnant women receive at least 1,500 mg of calcium per day, either through diet or supplementation, to reduce the risk of pre-eclampsia. In cases where dietary calcium intake is insufficient, calcium supplements may be recommended.</p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;">It is important to note that pre-eclampsia is a complex condition that can have various causes, and calcium supplementation alone may not prevent it in all cases. Other preventative measures such as maintaining a healthy lifestyle, attending regular prenatal checkups, and managing pre-existing health conditions can also help reduce the risk of pre-eclampsia.</p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;"><br /></p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 0px 0px 1.25em; white-space: pre-wrap;">Several studies have investigated the effectiveness of calcium supplementation in preventing pre-eclampsia. Here are some key findings:</p><ol style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; counter-reset: item 0; display: flex; flex-direction: column; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; list-style-image: initial; list-style-position: initial; margin: 1.25em 0px; padding: 0px 0px 0px 1rem; white-space: pre-wrap;"><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">A Cochrane review of 13 randomized controlled trials involving over 15,000 women found that calcium supplementation reduced the risk of pre-eclampsia by 55% in women with low calcium intake and by 24% in women at high risk for pre-eclampsia.</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">A meta-analysis of 21 trials involving over 23,000 women found that calcium supplementation reduced the risk of pre-eclampsia by 24%, with a greater effect seen in women with low dietary calcium intake.</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">A study published in the British Medical Journal found that calcium supplementation reduced the risk of pre-eclampsia by 66% in women with a history of pre-eclampsia.</p></li></ol><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;">Overall, the data suggests that calcium supplementation can be an effective preventative measure against pre-eclampsia, especially in women with low dietary calcium intake or a history of pre-eclampsia. However, it is important to note that calcium supplementation should only be taken under the guidance of a healthcare professional, as excessive calcium intake can have adverse effects.</p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;">When I asked to provide references:</p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;"><br /></p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 1.25em 0px 0px; white-space: pre-wrap;"><br /></p><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; margin: 0px 0px 1.25em; white-space: pre-wrap;">Sure, here are some references for the information I provided:</p><ol style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; background-color: #444654; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; color: #d1d5db; counter-reset: item 0; display: flex; flex-direction: column; font-family: Söhne, ui-sans-serif, system-ui, -apple-system, "Segoe UI", Roboto, Ubuntu, Cantarell, "Noto Sans", sans-serif, "Helvetica Neue", Arial, "Apple Color Emoji", "Segoe UI Emoji", "Segoe UI Symbol", "Noto Color Emoji"; font-size: 16px; list-style-image: initial; list-style-position: initial; margin: 1.25em 0px 0px; padding: 0px 0px 0px 1rem; white-space: pre-wrap;"><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2018;10(10):CD001059. doi:10.1002/14651858.CD001059.pub5</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">Hofmeyr GJ, Manyame S, Medley N, Williams MJ, Kramer MS, Duley L. Calcium supplementation commencing before or early in pregnancy, or food fortification with calcium, for preventing hypertensive disorders of pregnancy. Cochrane Database Syst Rev. 2019;10(10):CD011192. doi:10.1002/14651858.CD011192.pub2</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">Villar J, Abdel-Aleem H, Merialdi M, et al. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol. 2006;194(3):639-649. doi:10.1016/j.ajog.2005.10.831</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">Buppasiri P, Lumbiganon P, Thinkhamrop J, Ngamjarus C, Laopaiboon M. Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes. Cochrane Database Syst Rev. 2015;(2):CD007079. doi:10.1002/14651858.CD007079.pub3</p></li><li style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px; padding-left: 0.375em;"><p style="--tw-border-spacing-x: 0; --tw-border-spacing-y: 0; --tw-ring-color: rgba(59,130,246,0.5); --tw-ring-offset-color: #fff; --tw-ring-offset-shadow: 0 0 transparent; --tw-ring-offset-width: 0px; --tw-ring-shadow: 0 0 transparent; --tw-rotate: 0; --tw-scale-x: 1; --tw-scale-y: 1; --tw-scroll-snap-strictness: proximity; --tw-shadow-colored: 0 0 transparent; --tw-shadow: 0 0 transparent; --tw-skew-x: 0; --tw-skew-y: 0; --tw-translate-x: 0; --tw-translate-y: 0; border: 0px solid rgb(217, 217, 227); box-sizing: border-box; margin: 0px;">Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. N Engl J Med. 1997;337(2):69-76. doi:10.1056/NEJM199707103370201</p></li></ol>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-73998066686448644842023-03-10T06:02:00.001-05:002023-03-10T06:02:08.185-05:00Topic Discussion: Calcium and Pre-eclampsia<p style="text-align: left;"><span style="font-family: times;">Interesting data is emerging that calcium supplementation may help prevent pre-eclampsia(PEC). <a href="https://pubmed.ncbi.nlm.nih.gov/26155993/">There are in vitro studies that have </a><span style="background-color: white; word-spacing: 1.5px;"><a href="https://pubmed.ncbi.nlm.nih.gov/26155993/">demonstrated that calcium has an anti-inflammatory effect and reduces the endothelial activation and dysfunction resulting from trophoblastic debris in pre-eclampsia</a>. </span><span style="background-color: white; word-spacing: 1.5px;">This may be mediated through the effect of calcium on the nitric oxide synthetase pathway, and the subsequent increased <a href="https://pubmed.ncbi.nlm.nih.gov/6999886/">production of nitric oxide. </a></span></span></p><p style="text-align: left;"><span style="font-family: times;"><span style="word-spacing: 1.5px;"><br /></span><span style="word-spacing: 1.5px;"><a href="https://pubmed.ncbi.nlm.nih.gov/30277579/">At a population level</a>, there is some evidence that dietary calcium intake and incidence of PEC is inverse. This cochrane based review back in 2017 showed that </span><span style="background-color: white;">High-dose calcium supplementation (≥ 1 g/day) may reduce the risk of PEC and preterm birth, particularly for women with low calcium diets (low-quality evidence). The treatment effect may be overestimated due to small-study effects or publication bias. It reduces the occurrence of the composite outcome 'maternal death or serious morbidity', but not stillbirth or neonatal high care admission. There was an increased risk of HELLP syndrome with calcium supplementation, which was small in absolute numbers. The limited evidence on low-dose calcium supplementation suggests a reduction in PEC, hypertension and admission to neonatal high care. </span></span></p><p style="text-align: left;"><span style="font-family: times;"><span style="background-color: white; color: #212121;">A recent review in <a href="https://www.sciencedirect.com/science/article/pii/S0735109720362987">JACC</a> does put calcium in the benefit category for prevention of PEC.</span></span></p><p style="text-align: left;"><span style="font-family: times;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: times;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFcZ0B_3v1D9yK3bV8vlBwL_8IoH_WkbyalNiUv1n2px8Sd7ofAbGfxY_uV5C3tukWqV1jk8_VBnmgr54KiVG33Qtcr4NGIkU8sCHwIIz7uRDbPCQ2t5FooHxheJ3pSLdJw61XUk9QR-qZDILvWqfUZBm4lDqCUgNAU6txtmaBnad3mMP4KibfJUP9/s418/1-s2.0-S0735109720362987-gr2.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="269" data-original-width="418" height="258" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFcZ0B_3v1D9yK3bV8vlBwL_8IoH_WkbyalNiUv1n2px8Sd7ofAbGfxY_uV5C3tukWqV1jk8_VBnmgr54KiVG33Qtcr4NGIkU8sCHwIIz7uRDbPCQ2t5FooHxheJ3pSLdJw61XUk9QR-qZDILvWqfUZBm4lDqCUgNAU6txtmaBnad3mMP4KibfJUP9/w400-h258/1-s2.0-S0735109720362987-gr2.jpg" width="400" /></a></span></div><span style="font-family: times;"><br /><span style="background-color: white; color: #212121;"><br /><br /></span></span><p></p><p style="text-align: left;"><span style="font-family: times;"><span style="color: #212121;"><br /></span><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;">Then came the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31818-X/fulltext">CAP study</a> published in Lancet. <span style="background-color: white; word-spacing: 1.5px;">The CAP study was a double-blind RCT, which aimed to assess whether 500 mg of calcium supplementation before pregnancy and in early pregnancy prevents pre-eclampsia in a population group of women at a high-risk for PEC and with a generally low dietary calcium intake. In this study of 1,355 women with a history of PEC, <b>there was no difference</b> in the incidence of PEC between the treatment or placebo group (RR 0.80, 95% CI 0.61–1.06). However, the compliance rates were low (only 50% of the population took at least 80% of the expected tablets), which may limit the validity of these results. Interestingly, in a subgroup analysis of participants with adequate compliance (defined as >80%), the rate of PEC was significantly lower in the calcium group in comparison to the placebo controls (RR 0.66, 95% CI 0.44–0.98). Another limitation of this study was the dosage of calcium used, which at 500 mg appeared to be lower than the doses prescribed in previous trials.</span></span></p><p style="text-align: left;"><span style="font-family: times;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: times;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhR793qMChHB2DaCHzdjvi8w0g8r3wqAFsyqWAefoSqYFSgxsxFmdoTFkBxRtBVbvTYhAOUurEJRWsOS9ZUbqqpIUtPuOPKJpXPIv9kyYMxaZnvpB1ZiGKgckuy4UDOHCb77CTAk8hzXyd4coIQTWerOaP0Uy7dpy7yX5sDZG-Kw5tVQtQY8O4OUGIr/s1200/CAP-Study-Sept.-5-2019_page-0001.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="927" data-original-width="1200" height="309" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhR793qMChHB2DaCHzdjvi8w0g8r3wqAFsyqWAefoSqYFSgxsxFmdoTFkBxRtBVbvTYhAOUurEJRWsOS9ZUbqqpIUtPuOPKJpXPIv9kyYMxaZnvpB1ZiGKgckuy4UDOHCb77CTAk8hzXyd4coIQTWerOaP0Uy7dpy7yX5sDZG-Kw5tVQtQY8O4OUGIr/w400-h309/CAP-Study-Sept.-5-2019_page-0001.jpg" width="400" /></a></span></div><span style="font-family: times;"><br /><span style="background-color: white; word-spacing: 1.5px;"><br /></span></span><p></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;"><br /></span></p><p style="text-align: left;"><span style="font-family: times;">(Image from <a href="https://pre-empt.obgyn.ubc.ca/home-page/past-projects/cap/)">https://pre-empt.obgyn.ubc.ca/home-page/past-projects/cap/)</a> </span></p><p style="text-align: left;"><span style="font-family: times;">Finally, a more <a href="https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17222">recent meta-analysis </a>published is adding some mixed data. <span style="background-color: white; color: #1c1d1e;">The meta-analysis included </span><span style="background-color: white;">30 trials (</span><i style="background-color: white; box-sizing: border-box;">N</i><span style="background-color: white;"> = 20 445 women), and the network meta-analysis to evaluate calcium dosage included 25 trials (</span><i style="background-color: white; box-sizing: border-box;">N</i><span style="background-color: white;"> = 15 038). Calcium supplementation prevented PEC similarly with a high dose (RR 0.49, 95% CI 0.36–0.66) or a low dose (RR 0.49, 95% CI 0.36–0.65). By network meta-analysis, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43–1.40). Calcium was similarly effective regardless of baseline PEC risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake.</span></span></p><p style="text-align: left;"><span style="background-color: white;"><span style="font-family: times;">The authors conclude that by using direct and indirect trial evidence in meta-analysis and network meta-analysis, calcium supplementation (vs placebo/no therapy) decreases the incidence of PEC, defined traditionally as gestational hypertension and new proteinuria. This effect is similar with high- or low-dose calcium, regardless of baseline PEC risk, timing of calcium initiation. <i><b>But, the effectiveness of calcium is restricted to populations with low average baseline calcium intake. </b></i>The small increase (of an absolute 0.2%) in HELLP syndrome with calcium was more than balanced by a reduced incidence of death or severe maternal morbidity (by 1.0%). </span></span></p><p style="text-align: left;"><span style="font-family: times;">In summary, very fascinating science here and perhaps something that needs a closer look. At this point, based on data, perhaps women with low calcium intake maybe the best that benefit from this preventive strategy. The <span style="background-color: white; word-spacing: 1.5px;">International Federation of Gynecology and Obstetrics (FIGO),</span><span style="background-color: white; word-spacing: 1.5px;"> women with low calcium intake (<80 mg/day) calcium replacement (<1 g/day) or supplementation (1.5–2 g/day) is recommended. </span><span style="background-color: white;">In populations where baseline dietary calcium intake is low, the World Health Organization recommends for 1500 to 2000 mg elemental calcium supplementation per day for pregnant individuals to reduce the risk of PEC, particularly among those at higher risk of developing hypertension</span><span style="background-color: white;">. The WHO recommendation is based on positive results from systematic reviews as discussed above</span><span style="background-color: white; color: #232323;">.</span></span></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-62067744275178467752023-02-25T18:30:00.003-05:002023-02-25T18:30:19.256-05:00Golden Era in therapeutics for IgA Nephropathy<p><span style="font-family: arial;">Just in the last 1 year, we have two new drugs being approved for IgA Nephropathy. In addition, we have seen an emergence in using SGLT2i perhaps in IgAN and other GNs. The DAPA-CKD trial IgAN patients were evaluated and the use of dapagliflozin was superior than placebo. The EMPA-Kidney had close to 800 IgAN patients, we shall await those results soon.</span></p><p><span style="font-family: arial;"><br /></span></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEg-ewEknnnFQafmGK1YKD-mSMKVsR9eQTroXYB7VmYQf50cseQ0_fuqZlnBf3o-VgZMUpx5rUck-OwErCPNQrrYhmVx0sGRI9VuSdj4FOsCuAOM6TS4j9T29K4tBORDYkeE3Cv2eXflPXpSSg4AwsNkWzWUw468bXYvcFkLtR-a3xZEsDZgy-rHP9CM" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="914" data-original-width="1625" height="225" src="https://blogger.googleusercontent.com/img/a/AVvXsEg-ewEknnnFQafmGK1YKD-mSMKVsR9eQTroXYB7VmYQf50cseQ0_fuqZlnBf3o-VgZMUpx5rUck-OwErCPNQrrYhmVx0sGRI9VuSdj4FOsCuAOM6TS4j9T29K4tBORDYkeE3Cv2eXflPXpSSg4AwsNkWzWUw468bXYvcFkLtR-a3xZEsDZgy-rHP9CM=w400-h225" width="400" /></a></div><br /><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800997">MMF </a>has just made a come back with a recent Chinese study showing some promise in a RCT. </span></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEjdY5l-7fyS1PkOm77VkJkrjfl44JX9ZbIuevQTgJpjVK7bzAQGfxBDH1ENBn56F4zBJrKD6KbcpyhCldgBmAZWguyLSZHzm6HVMQ_ZvEpA5kh0qcCVfR3fejQ6OCwh-r4FwHTNJ4MzZZTsHULIasexxXIR7-CMzBMYLgVhjRN0qGIOQ7652Rfiwgi2" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="457" data-original-width="810" height="226" src="https://blogger.googleusercontent.com/img/a/AVvXsEjdY5l-7fyS1PkOm77VkJkrjfl44JX9ZbIuevQTgJpjVK7bzAQGfxBDH1ENBn56F4zBJrKD6KbcpyhCldgBmAZWguyLSZHzm6HVMQ_ZvEpA5kh0qcCVfR3fejQ6OCwh-r4FwHTNJ4MzZZTsHULIasexxXIR7-CMzBMYLgVhjRN0qGIOQ7652Rfiwgi2=w400-h226" width="400" /></a></div><br /><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><span style="font-family: arial;">Finally, a targeted release steroid called budesonide has been FDA approved. This was developed to deliver the active drug in the distal ileum, where the Peyer's patches are -- the likely culprit where a large amount of galactose deficient IgA is made. The data was just published in KI.</span></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><br /></span></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEjx9Brq_0S3zsJpwTClbZQpv90c6BaMfvNKQiFtxkfgbwZjiTINYOIK7_3oW569mRvYU9DxJ-WSmvjwz2i1lpmczH_sETVWS6Wjb0aELlW1_oczlkSf2uh9CWrQYcVfAVwnQwI3DxSCfka0V9V6VD0wI1yY_3kStE5xJXsglQjPX-Zq6dqZHbAylgNt" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="815" data-original-width="1447" height="225" src="https://blogger.googleusercontent.com/img/a/AVvXsEjx9Brq_0S3zsJpwTClbZQpv90c6BaMfvNKQiFtxkfgbwZjiTINYOIK7_3oW569mRvYU9DxJ-WSmvjwz2i1lpmczH_sETVWS6Wjb0aELlW1_oczlkSf2uh9CWrQYcVfAVwnQwI3DxSCfka0V9V6VD0wI1yY_3kStE5xJXsglQjPX-Zq6dqZHbAylgNt=w400-h225" width="400" /></a></div><br /><br /><p></p><p><br /><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><span style="font-family: arial;">And finally, the f<span style="text-align: -webkit-center;">irst single molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA) approved for use in patients with IgAN. <a href="chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216403s000lbl.pdf">The data is not published yet in a journal.</a></span></span></p><p><span style="font-family: arial;">There are still ongoing trials of other DEARAs, and complement inhibitors, APRIL inhibitors for IgAN. </span><span style="font-family: arial;">In my opinion, the future of treatment of IgAN can be perhaps summarized in the below figure: </span><span style="font-family: arial;">( created using biorender.com)</span></p><p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEi0ERrHL6UhD2SxpI7_wlPLBiR7TmztBee5PX1s4AzJ7jyHzx1ip9ICaoNprRdqXeNeSSc0Hy4Gp7yzsrhgIslYpu0R5G-il0sr2ep2q9V2igNQKVDRTQdH_MvGMvpmNvpB0s1Gr6A-ChH8lUNVfDe2mmRS-7OnIL-3gcX7VdyzyP9gI6FXnhMjKJiW" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img alt="" data-original-height="1013" data-original-width="1448" height="280" src="https://blogger.googleusercontent.com/img/a/AVvXsEi0ERrHL6UhD2SxpI7_wlPLBiR7TmztBee5PX1s4AzJ7jyHzx1ip9ICaoNprRdqXeNeSSc0Hy4Gp7yzsrhgIslYpu0R5G-il0sr2ep2q9V2igNQKVDRTQdH_MvGMvpmNvpB0s1Gr6A-ChH8lUNVfDe2mmRS-7OnIL-3gcX7VdyzyP9gI6FXnhMjKJiW=w400-h280" width="400" /></a></span></div><span style="font-family: arial;"><br /><br /></span><p></p><p></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-7368231124965152792023-02-24T12:48:00.005-05:002023-02-24T12:48:42.936-05:00Peritoneal Dialysis in Figures<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFV4ecU1DUAvS--06rnCYf74GSIRFHxzbt_aP0fQ9BO9Ws0VFI8j7aVIgO12JHpdZHMZ6-ffq8pe6aNrZGX4EsiiCx0rLM3WkAzp7Ra-nHzvee5M-EGsOQib3bjutLicM0gwcXqPgzx962KNHBam-b6kxnvsdkS5cDYc4hrgeH4c-7YziRPZ_nk1lD/s1560/PD2.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="1560" data-original-width="1345" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFV4ecU1DUAvS--06rnCYf74GSIRFHxzbt_aP0fQ9BO9Ws0VFI8j7aVIgO12JHpdZHMZ6-ffq8pe6aNrZGX4EsiiCx0rLM3WkAzp7Ra-nHzvee5M-EGsOQib3bjutLicM0gwcXqPgzx962KNHBam-b6kxnvsdkS5cDYc4hrgeH4c-7YziRPZ_nk1lD/w345-h400/PD2.jpg" width="345" /></a></div><br /><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiJii5Uq_jqXffPWirmviUhT0c7odh2Xkze_Ig29zSS7EnX8VXbVGGar7C-5gAZU1CTBhDG_wpvHeea2MNX7BeMDFlZsf8X4QTcGYLslb9RNvesPK_QXHSSO9GzM2dz_bjC22Wxs9xruoxhL7zYoSvjoBpqh6jNHJdhs-YsZYNNYhZ9qUouxgRD_LPl/s1333/PD1.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="1333" data-original-width="1307" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiJii5Uq_jqXffPWirmviUhT0c7odh2Xkze_Ig29zSS7EnX8VXbVGGar7C-5gAZU1CTBhDG_wpvHeea2MNX7BeMDFlZsf8X4QTcGYLslb9RNvesPK_QXHSSO9GzM2dz_bjC22Wxs9xruoxhL7zYoSvjoBpqh6jNHJdhs-YsZYNNYhZ9qUouxgRD_LPl/w393-h400/PD1.jpg" width="393" /></a></div><div><br /></div><div><br /></div><div class="separator" style="clear: both; text-align: center;"><br /></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh6Wwxf8pwhA0TT1H7DaXXSSMf70o4putCwNdLJWWoY7MmQKtOHGA7z3yFLrEabxooJrILezA4xvczOP8sPYVSv-4h0935JiCb-OxEJVW_FyHo-Hv8XKzbWiccc94NqEcrmSSsOG2Xib-pWI91PxH-04Ie1QSs2qXoTpObL8gG5donOZqtImd3FEqCc/s1509/PD3.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="1509" data-original-width="1323" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh6Wwxf8pwhA0TT1H7DaXXSSMf70o4putCwNdLJWWoY7MmQKtOHGA7z3yFLrEabxooJrILezA4xvczOP8sPYVSv-4h0935JiCb-OxEJVW_FyHo-Hv8XKzbWiccc94NqEcrmSSsOG2Xib-pWI91PxH-04Ie1QSs2qXoTpObL8gG5donOZqtImd3FEqCc/w351-h400/PD3.jpg" width="351" /></a></div><br /><div class="separator" style="clear: both; text-align: center;"><br /></div><br /><p style="text-align: left;"><span style="font-size: x-small;">References:<br /></span><a href="https://www.sciencedirect.com/science/article/pii/S0272638622008484?via%3Dihub" style="font-family: ElsevierGulliver, Georgia, "Times New Roman", STIXGeneral, "Cambria Math", Arial, Helvetica, "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif; font-size: small;">Peritoneal Dialysis Prescription and Adequacy in Clinical Practice: Core Curriculum 202</a><span style="color: #2e2e2e; font-family: ElsevierGulliver, Georgia, "Times New Roman", STIXGeneral, "Cambria Math", Arial, Helvetica, "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif; font-size: small;">3</span></p><div style="text-align: left;"><p style="background-color: white; color: #666666; font-family: "Trebuchet MS", Trebuchet, Verdana, sans-serif;"><span style="font-size: x-small;"><b>S</b><b>pecial post by </b></span></p><p class="MsoNormal" style="background-color: white; color: #666666; font-family: "Trebuchet MS", Trebuchet, Verdana, sans-serif;"><b><span style="font-size: x-small;">Lakshmi Kannan, MBBS, MD, <o:p></o:p></span></b></p><p class="MsoNormal" style="background-color: white; color: #666666; font-family: "Trebuchet MS", Trebuchet, Verdana, sans-serif;"><b><span style="font-size: x-small;">Department of Nephrology, Pikeville Medical Center<o:p></o:p></span></b></p><p class="MsoNormal" style="background-color: white; color: #666666; font-family: "Trebuchet MS", Trebuchet, Verdana, sans-serif;"><b><span style="font-size: x-small;">Adjunct Faculty, University of Pikeville Kentucky College of Osteopathic Medicine<o:p></o:p></span></b></p><p class="MsoNormal" style="background-color: white; color: #666666; font-family: "Trebuchet MS", Trebuchet, Verdana, sans-serif;"><b><span style="font-size: x-small;">Kentucky, USA</span></b></p></div><div style="text-align: left;"><br /></div><div><br /></div><div><br /></div><div><br /></div><div><br /></div><br /><p></p><div><br /></div><div class="separator" style="clear: both; text-align: center;"><br /></div><br />Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-83467225847106500652023-02-16T10:56:00.002-05:002023-02-16T10:56:35.361-05:00Concept Map: Kidney Involvement in Erdheim Chester Histiocytosis<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoJKjQFRfqNDwbF03a_ZFSiAU-ly4FNf72YFkYJT0RbIMeZ2QK3TAE80VDS6HY_US61Dy_IkRIyxMA5jgIWnzrAj2xR7X4epmw8vj-2fCPSy7mRqw2INBRU8415FpuJPS7tH3YI1bGhwJH8mPY0KsLMaKop0w3MdGIKaetxiZ86P695O8ue58Z1khY/s3000/EC%20histiocytosis%20and%20Kidney.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoJKjQFRfqNDwbF03a_ZFSiAU-ly4FNf72YFkYJT0RbIMeZ2QK3TAE80VDS6HY_US61Dy_IkRIyxMA5jgIWnzrAj2xR7X4epmw8vj-2fCPSy7mRqw2INBRU8415FpuJPS7tH3YI1bGhwJH8mPY0KsLMaKop0w3MdGIKaetxiZ86P695O8ue58Z1khY/w400-h280/EC%20histiocytosis%20and%20Kidney.jpg" width="400" /></a></div><br /><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p>This concept map in inspired by work in this paper by<a href="https://pubmed.ncbi.nlm.nih.gov/36374823/"> Chazal et al in Kidney International</a></p><p> </p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-73500862444425662022023-01-11T16:49:00.002-05:002023-01-11T16:49:26.285-05:00Concept Map: Onco-HTN( cancer therapy related HTN)<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgfngDPXo-RF17rYLmRDMZV3TxEYOBySWYHcA3wCN7WYnYELLCmB9Eyvq7GU2PBjl1Om4YH1OHsZOcwqe7OHOGY-YEatAeVYAienc-nguK5Iz_g-ILgmt70nC2BOOViSRgPS2WhZk__zIqsQazfxLFv7jGiEx8hQM_wYLQXoXqqAg5KSfOyeIokyyAT/s3000/Onco-HTN2023.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgfngDPXo-RF17rYLmRDMZV3TxEYOBySWYHcA3wCN7WYnYELLCmB9Eyvq7GU2PBjl1Om4YH1OHsZOcwqe7OHOGY-YEatAeVYAienc-nguK5Iz_g-ILgmt70nC2BOOViSRgPS2WhZk__zIqsQazfxLFv7jGiEx8hQM_wYLQXoXqqAg5KSfOyeIokyyAT/w400-h280/Onco-HTN2023.jpg" width="400" /></a></div><br /><p></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><br /></p><p><a href="https://www.ahajournals.org/doi/10.1161/HYP.0000000000000224">Based on a recent AHA scientific statement, a concept map on onco-HTN</a></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0tag:blogger.com,1999:blog-5872673930112727345.post-53019643644505267982023-01-06T06:37:00.000-05:002023-01-06T06:37:00.237-05:00NELL-1 Membranous Nephropathy- Concept Map<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpeNUvuFWJQKLwab_088ftPBOnI1eTOMssehZIn4dgTN6kTnEyLCszilrj5wgZatb5Rb-dGHWNlB1Byj7Na71Zv27XgLqsQfGNNgvdHR_V6Ma6enwIOWk8HY004qrTdwy9datwzk_tUoyJ_lajTO_c0YX6R384xYtp7Aa0kz1SnGj38KX7t_ACuSzI/s3000/Causes%20of%20NELL-1%20MN.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="2100" data-original-width="3000" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpeNUvuFWJQKLwab_088ftPBOnI1eTOMssehZIn4dgTN6kTnEyLCszilrj5wgZatb5Rb-dGHWNlB1Byj7Na71Zv27XgLqsQfGNNgvdHR_V6Ma6enwIOWk8HY004qrTdwy9datwzk_tUoyJ_lajTO_c0YX6R384xYtp7Aa0kz1SnGj38KX7t_ACuSzI/w400-h280/Causes%20of%20NELL-1%20MN.jpg" width="400" /></a></div><br /><div class="separator" style="clear: both; text-align: center;"><br /></div><br /><p></p><p><br /></p><p>This is an inspired figure from <a href="https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfac237/6780213">Sethi's amazing review in CKJ. </a></p><p>This figure is a summary of the various secondary causes of NELL-1 MN that have been described. <br />( keeping in mind that primary NELL-1 MN without a secondary cause still is the most common)</p><p><br /></p>Kenar D Jhaveri( kidney 007)http://www.blogger.com/profile/08654527832183917798noreply@blogger.com0