We know MUDPILES
Then came GOLDMARK
There are other causes of a true high anion gap metabolic acidosis that are not captured by the MUDPILES and GOLDMARK mnemonics that should be kept in mind and are included in the recently published and modified CUTE DIMPLES mnemonic presented in CJASN by Anika A et al.
This is a schematic of the treatment of resistant HTN in the hemodialysis patient. Based on a review published in JASN
Figure made using biorender.com
Check out this twitter feed I had done on the topic of Intravitreal Anti VEGF agents and the Kidney.
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 fascinating new study 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.
Image courtesy: pathologyoutlines.com
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.
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After PLA2R, NELL-1 related membranous nephropathy(MN) seems to be the second most common MN. Initially, the studies had pointed towards a cancer-related cause for NELL-1 MN. In recent years and most recently, 2 papers published in 2024 highlight the role of complementary medications.
A study from India 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.
A study spanning three institutions 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.
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).
What is this entity? Tumor Genesis Syndrome compared to Tumor Lysis Syndrome.
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.
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.
In their literature review, Chan et al. 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, Zakaria et al. 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, Radi 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, Aderka et al. 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, another case 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.
Tumor Genesis Syndrome is a rare syndrome that needs to be considered in the differential diagnosis of hypophosphatemia.
Not much has been written regarding the role of a nephro-hospitalists in the Nephrology literature. There is one perspective back in 2019, 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.
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.
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.
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.
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.
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.
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.
What have other fields done
Check out this regarding the role of onco-hospitalists and cancer hospitals.
Other fields such as GI and Neurology as well have adopted this model.
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.
