Topic Discussions: Auto antibodies in diffuse podocytopathies

Recent advances have reshaped how we view nephrotic syndrome moving from descriptive pathology to a mechanism-based model. A growing body of evidence shows that circulating autoantibodies against key slit diaphragm proteins—nephrin, podocin, and Kirrel1—play a central role in many cases of autoimmune podocytopathy. This was also confirmed in pediatric literature. 

These discoveries promise earlier, less invasive diagnosis and more precise, personalized treatment.

Yet, translating these insights into clinical practice is far from straightforward. The antibodies are often present at very low or transient levels, disappearing into the urine during active disease. Their titers fluctuate with relapses and remissions, complicating the timing of tests. Moreover, NS is heterogeneous: while many patients have anti-nephrin antibodies, others harbor antibodies to podocin or Kirrel1, and some exhibit overlapping profiles through “epitope spreading.”

Technical challenges also hamper detection. Assay performance depends on antigen fragment choice, expression system, and protein modifications—especially for the heavily glycosylated nephrin. To improve reliability, researchers emphasize combined strategies, pairing ELISA with high-resolution biopsy techniques like super-resolution microscopy.

The article proposes a roadmap: develop multiplex assays, standardize antigen design, integrate biopsy validation, and pursue longitudinal studies. Success could enable precision diagnostics and tailored therapy, transforming care for children and adults with nephrotic syndrome.

Is it time for targeted therapies for Glomerular Diseases?

Topic Discussion: Pseudo AKI with anti cancer agents

Legend: AKI, acute kidney injury, MATE, multidrug and toxic compound extrusion; OAT, organic anion transporter; OCT, organic cation transporter

As of April 2024--most updated data on anti-cancer agents and Pseudo-AKI.

Several classes of cancer treatments are associated with pseudo-AKI.  Providers must be aware of this phenomenon, as pseudo-AKI can lead to temporary stopping and even permanent discontinuation of life-saving treatments. When patients present with increases in serum creatinine while on these drugs, checking a serum cystatin C level may help differentiate true AKI from pseudo-AKI.

Shruti Gupta and Kenar Jhaveri 

Anion gap acidosis- CUTE DIMPLES

We know MUDPILES

Then came GOLDMARK

 

Now let's welcome-- CUTE DIMPLES

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. 

Topic Discussion: Hyponatremia with Spironolactone

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.

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.

In another paper, 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.

Is it possible that a combination of a thiazide and a K⁺-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.

What about the concept of vasopressin escape? During hyponatremia, the body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape 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. Vasopressin escape was also blunted in rats given spironolactone, a mineralocorticoid receptor blocker. The authors results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.

    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.

Topic Discussion: Mastocytosis and the Kidney

 

A recent review by us in NDT discusses the kidney involvement in systemic mastocytosis.

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. SM manifests as symptoms related to mast cell mediator release (flushing, pruritus, cramps, diarrhea, bronchospasm, angioedema) and organ damage. Skin involvement is frequent, esp. in indolent SM, red-brown macules and papules, fine telangiectasias, urticate on stroking

Kidney involvement: 1)Paraprotein-related kidney disease like light chain amyloidosis and MIDD, common association between plasma cell dyscrasia and SM 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. 3)nephrotoxicity of drugs to treat SM: IFN-alpha, bisphosphonates, tyrosine kinase inhibitors

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

5)bladder mast cell infiltration causing interstitial cystitis

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.

Although rare, kidney involvement is increasingly described, either direct or indirect

Topic Discussion: Atypical anti GBM disease

 

We are aware that circulating 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.

Atypical anti-GBM disease is considered when patients have linear IgG deposition along the glomerular basement membrane without anti-GBM antibodies in the circulation.

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.

Pathogenesis:

(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

(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

(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

Pathology: (i) Lack diffuse crescentic and necrotizing glomerulonephritis, (ii). Light microscopy heterogenous: mesangial and/or endocapillary proliferative GN, MPGN, FSGS, mesangial sclerosis; and glomerular endothelial changes resembling TMA are common

Monotypic atypical anti-GBM disease: 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?

Prognosis: 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.

Treatment: is individualized and typically consists of immunosuppressive agents used to treat classic anti-GBM disease or monotherapy with renin-angiotensin-aldosterone blockers

Check out this review

Topic Discussion: Calcium and Pre-eclampsia- using AI

 I now am re-doing the post on using calcium to prevent pre-eclampsia using artificial intelligence website- https://chat.openai.com/chat 

Prompt: Can calcium prevent PEC?

Response: 

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.

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.

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.

Several studies have investigated the effectiveness of calcium supplementation in preventing pre-eclampsia. Here are some key findings:

1. 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.

2. 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.

3. 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.

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.

When I asked to provide references:

Sure, here are some references for the information I provided:

1. 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

2. 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

3. 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

4. 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

5. 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

Topic Discussion: Calcium and Pre-eclampsia

Interesting data is emerging that calcium supplementation may help prevent pre-eclampsia(PEC). There are in vitro studies that have demonstrated that calcium has an anti-inflammatory effect and reduces the endothelial activation and dysfunction resulting from trophoblastic debris in pre-eclampsia. This may be mediated through the effect of calcium on the nitric oxide synthetase pathway, and the subsequent increased production of nitric oxide. 

At a population level, there is some evidence that dietary calcium intake and incidence of PEC is inverse. This cochrane based review back in 2017 showed that 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. 

A recent review in JACC does put calcium in the benefit category for prevention of PEC.

Then came the CAP study published in Lancet. 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, there was no difference 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.

(Image from https://pre-empt.obgyn.ubc.ca/home-page/past-projects/cap/) 

Finally, a more recent meta-analysis published is adding some mixed data. The meta-analysis included 30 trials (N = 20 445 women), and the network meta-analysis to evaluate calcium dosage included 25 trials (N = 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.

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. But, the effectiveness of calcium is restricted to populations with low average baseline calcium intake. 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%). 

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 International Federation of Gynecology and Obstetrics (FIGO), women with low calcium intake (<80 mg/day) calcium replacement (<1 g/day) or supplementation (1.5–2 g/day) is recommended. 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. The WHO recommendation is based on positive results from systematic reviews as discussed above.

Golden Era in therapeutics for IgA Nephropathy

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.

MMF has just made a come back with a recent Chinese study showing some promise in a RCT. 

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.

And finally, the first single molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA) approved for use in patients with IgAN. The data is not published yet in a journal.

There are still ongoing trials of other DEARAs, and complement inhibitors, APRIL inhibitors for IgAN. In my opinion, the future of treatment of IgAN can be perhaps summarized in the below figure: ( created using biorender.com)

Opinion- Renal Thrombotic Microangiopathy?- Should we be calling it Renal Limited Endothelial injury or Endothelial Injury of Renal Significance

Thrombotic Microangiopathy- what’s in a name?

This is a common conversation:

“ The kidney biopsy confirms TMA”.  Great- we should ask hematology to help treat..
Hematology—“ but there are no signs of microangiopathic hemolytic anemia.. no schistocytes on smear—no need to treat”

Another conversation

“ The kidney biopsy confirms TMA”.  But there are no micro thrombi on the kidney biopsy. This is likely from HTN—treat the HTN.  “ but the patient has a complement factor H mutation..”.. hmm..

The presentation of TMA can be as mild as HTN only, or AKI on CKD or HTN with CKD or nephritic syndrome or nephrotic syndrome or just nephrotic range proteinuria with AKI. The clinical presentation is very varied. I have seen it all.

The problem with TMA starts with the nomenclature.  Personally, I have a problem with a series of diseases in the kidney called TMA—some have angiopathy only, some have endotheliosis, some have both and some have additional microthrombi but at the end we call all of them TMA.

Most of TMA cases are without thrombosis, only rarely would you see true thrombi.  Frank thrombosis is more common in (catastrophic) APLAS associated TMA in the kidney.

Some TMA tends to be more glomerular  classically in pregnancy related, for example, with endothelial cell swelling = endotheliosis).  And some TMA tends to be more arterial (thrombotic angiopathy rather than microangiopathy). Or we might be catching them at various points in time. A continuous process..

 In my opinion, a better terminology of this entity should be Renal limited endothelial injury or endothelial injury of renal significance. Renal limited TMA without systemic findings is common-- very common than we think and we may be missing to treat as most likely don't get a renal biopsy. Systemic findings of MAHA or other endothelial injury are not required. In several cases- the injury is purely renal limited.  

The pathology is also variable and hence should be considered to be defined perhaps with what is noted on it. 

Endothelial injury with angiopathy
Endothelial injury with micro thrombi
Endothelial injury with endotheliosis predominant

The cause of the injury than can be defined better based on history of the patient and then divided into categories as per the syndromes of TMA or better called “endothelial injury”- such as ADAMTS13 mediated, complement mediated, Drug induced ( immune vs toxic), Shiga toxin mediated, metabolism mediated, coagulation mediated and so forth. This figure is from the classic NEJM article by George et al in 2014.

As we learn more about renal endothelial injury, perhaps a better practical terminology may be useful in defining the disease to help clinicians guide the treatment plan.

Topic Discussion: Ever changing FSGS classifications

FSGS is a tough diagnosis and often confusing to the Nephrologist. Classifications in FSGS also have been very confusing and challenging. Several years ago, the pathology based classification had entered all textbooks. 

Is this classification clinically useful? Not sure it is to most nephrologists? If I have a tip variant FSGS, or Perihilar, does it tell me anything re the cause and outcome? Maybe- but mostly not.

In 2007, there was a movement towards changing the concept to more podocytopathy based. ( see below- recreated using biorender). 

Not sure if this is useful either but it really asked a fundamental question re how we are seeing these spectrum of diseases we term FSGS.

The most useful to me personally is classifying the FSGS presentation into 

1) primary vs secondary cause

2) nephrotic syndrome vs nephrotic range proteinuria

While not 100% in most cases, nephrotic syndrome and FSGS usually is going to have a primary cause( sparing some genetic causes and viruses). In addition, what is also helpful from a pathology standpoint is not the LM, but the EM-- 

3) Is there diffuse or partial foot process effacement?- Usually the former responds to treatment better with steroids or other immunosuppression and later is more likely a secondary cause. It may also aid in looking for a secondary cause.

This figure from a JASN paper by De Vriese et al is very helpful indeed. 

So FSGS really should be described more in terms of primary vs secondary causes and EM findings to help in treatment decisions. Classically, your "permeability or immune mediated" FSGS should respond to treatment and would fit under nephrotic syndrome, diffuse foot process effacement and classically your primary FSGS.  Secondary FSGS from various causes like low nephron mass, obesity, viral , meds- all classically would have nephrotic range proteinuria and sporadic foot process effacement on EM. That being said, some genetic causes of FSGS would be seen to have diffuse foot process effacement as well. Genetic FSGS is an important one to keep in mind and screening for genetic causes should be done: young patient, family hx, resistant to treatment, aiding in post transplant risk. etc.

KDIGO GN 2021 guidelines summarize this nicely

APOL-1 plays an important cause and role here and this slide can summarize the primary and the second hit concept with APOL-1 related FSGS

We should not forget --nonspecific scarring on renal biopsies. FSGS should also be differentiated from focal segmental scarring that develops in immune-mediated GN (e.g., Membranous Nephropathy, IgA Neph, ANCA-associated GN, and lupus nephritis) as a result of post-inflammatory scarring of necrotizing or proliferative lesions. This happens a lot and this should not be treated as FSGS. 

In summary, FSGS has come a long way and finally we are seeing some changes in the way we are describing it.. Best 3 ways to categorize FSGS is clinically and EM based.

1. Primary vs Secondary

2. Nephrotic syndrome vs nephrotic range proteinuria

3. Diffuse foot process effacement vs partial foot process effacement 

Topic Discussion: CDK4/6 inhibitors and the Kidney

Selective estrogen receptor inhibitors and aromatase inhibitors are the mainstay of therapy for hormonal receptor-positive (HR+) breast cancer; however, most metastatic HR+, human epidermal growth factor receptor 2-negative (HER2-) progress and acquire resistance to endocrine therapies. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6 inhibitors) comprise a new class of drugs that overcome this resistance.  Three CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—have been approved for HER2-negative metastatic breast cancers, usually in combination with hormone therapy. 

Interestingly, the renal community has seen elevated serum creatinine associated with these agents. Several early trials of palbociclib and ribociclib did not describe the incidence of AKI, whereas clinical trials of abemaciclib have reported that up to 25% of patients experienced a rise in creatinine. In vitro studies of abemaciclib have shown that the drug and its major metabolites inhibit renal transporters like organic cation transporter-2, multidrug and toxin extrusion-1 (MATE-1), and MATE2-K, potentially leading to a reversible rise in creatinine without actually changing GFR. Cases have been described that show this pseudo-AKI. 

More recently, biopsy proven cases of acute tubular injury also have been noted- 6 cases with tubular and interstitial damage.

Finally, a search of the FAERs database revealed that, in addition to AKI, metabolic disturbances like hypokalemia, hyponatremia, and hypocalcemia may occur while on CDK4/6 inhibitors. Hyponatremia has been reported with ribociclib and with abemaciclib and grade 2 hypokalemia was reported in 20.8% of patients taking abemaciclib. 

In summary, the common renal associations with CDK4/6 inhibitors are

Pseudo AKI, ATI, hyponatremia, hypokalemia and hypocalcemia

Hypocomplementemia and the Kidney

 When we are faced with AKI and classically low c3 and c4, certain diseases come to mind.

A classic figure that has been used for years is below:

I think we can divide the low complement diseases and the kidney with glomerular processes and non glomerular processes

The glomerular diseases that are classically associated with low complements are:

MPGN pattern( all forms, c3GN, DDD, immune complex related MPGN), Lupus related GN, Cyro related GN, infection associated GN( both post strep and endocarditis), but we should not forget Fibrillary GN ( especially if MPGN pattern of injury is noted) and heavy chain deposition disease(HCDD). Finally, we should not forget TMA with complement disorders can cause low c3 in some cases.  In other words, immune complex is the main pathology that is driving the hypocomplementemia. 

Non glomerular diseases that can be associated with low complements should be kept in mind- classically atheroembolic disease and IgG4 diseases( fair amount have low complements)

Here is a mnemonic that many use- CHAMPS ( created by NephSim)

Topic Discussion: As needed anti HTN meds in the hospital- can we stop the madness?

 

We often see in the hospital, BP is treated as needed. Often, as nephrologists we have suggested to NOT do this. Outpatient problem that exists for years cannot be corrected in 2 hours by hydralazine or beta blockers so that the "vitals" look good and " numbers" are good for rounds. A recent study published in Hypertension nicely showcases this via a retrospective propensity matched protocol. When compared to scheduled BP meds patients to Scheduled meds and PRN patients ( over 4000 each), risk of AKI, stroke and mortality was higher in the as needed group. In addition, length of stay was higher as well. 

This comes following another recent article in JAMA looking at a similar concept. Among 22,000+ patients studied in hospitals with non cardiac diagnosis, hypertension was treated as needed in several patients.  In a propensity-matched sample controlling for patient and BP characteristics, treated patients had higher rates of subsequent acute kidney injury (466 of 4520 [10.3%] vs 357 of 4520 [7.9%]; P < .001) and myocardial injury (53 of 4520 [1.2%] vs 26 of 4520 [0.6%]; P = .003). There was no BP interval in which treated patients had better outcomes than untreated patients. A total of 1645 of 17 821 patients (9%) with hypertension were discharged with an intensified antihypertensive regimen. Treating with intensification of anti HTN meds without signs of end organ damage lead to worse outcomes.

Finally, another study in 2019 in JAMA found that among older adults hospitalized for noncardiac conditions, prescription of intensified anti-hypertensives at discharge was not associated with reduced cardiac events or improved BP control within 1 year but was associated with an increased risk of readmission and serious adverse events within 30 days.

So basically, let's not try to treat a number but the patient and let's not make a chronic problem a priority in the admission that doesn't warrant too many changes. That may be doing some harm!

Opinion: Impact factors and Renal Journals( Kidney Journals or Nephrology Journals)

When we observe, no nephrology journal that published original investigations had an impact factor of >10.0 till 2021. Cardiology, Oncology and Gen Med journals top the lists usually with high impact factor in the 90s, 70s, 60s but obviously in the two digits. It is good to see finally that two of our journals KI and JASN have entered the two digits, both flagship journals of ISN and ASN. 

What is an impact factor? (IF). It is an index calculated by Clarivate that reflects the yearly avg number of citations of articles published in the last 2 years in a given journal, as indexed by the web of science. In the academic world, this matters as journals with high IF values are often deemed as more important and carry more prestige. Several promotional meetings at med schools also take this metric as the most important on where the candidate's work is published. Lower IF journals or higher IF journals

Despite it's shortcomings, IF and the author's citation index( h-index), such judgements remain common practice suggesting a need for an alternative method. Some have proposed something called the relative citation ratio( RCR).  It is an improved method to quantify the influence of a research article by making novel use of its co-citation network—that is, the other papers that appear alongside it in reference lists—to field-normalize the number of times it has been cited, generating a RCR. Since choosing to cite is the long-standing way in which scholars acknowledge the relevance of each other’s work, RCR can provide valuable supplemental information, either to decision makers at funding agencies or to others who seek to understand the relative outcomes of different groups of research investments.

One should read this interesting tweet on this topic

We have a broken system in science. Currently, the main bulwark still protecting science from total collapse in the US is the NIH scientific review system.

I know this may sound extreme. But hear me out. 1/N

— Mara Mather (@MaraMather) June 29, 2021

Also, check out this amazing post by Curry on " Sick of Impact Factor" . He says that that real problem started when IF began to be applied to papers and people. He says and I quote, 

" I can’t trace the precise origin of the growth but it has become a cancer that can no longer be ignored. The malady seems to particularly afflict researchers in science, technology and medicine who, astonishingly for a group that prizes its intelligence, have acquired a dependency on a valuation system that is grounded in falsity. We spend our lives fretting about how high an impact factor we can attach to our published research because it has become such an important determinant in the award of the grants and promotions needed to advance a career. We submit to time-wasting and demoralizing rounds of manuscript rejection, retarding the progress of science in the chase for a false measure of prestige."

Some not so perfect options/alternatives for IF are on this website.  Here is the chemistry world's revolt against it. This one study showed that an Article Influence score (AIS) and Source Normalized Impact per Paper (SNIP) were the only bibliometric alternatives to demonstrate a positive correlation when compared to the IF (r = 0.94) and (r = 0.66) respectively.

Interesting discussion on twitter on the recent announcement of renal journal IFs. 

Nephrology specific impact factors: KI 10.6, Jasn 10.1, AJKD 8.8, CJasn 8.2, NDT 5.99, clinical kidney journal 4.5, KI Reports 4.1

— Manish M Sood MD MSc FRCPC (@Msood99M) June 30, 2021

So, what should renal journals do? Should we be leaders in medicine and change the tide or try a stick with the old ways and continue using the IF? 

In the NEWs: Hydralazine and the Kidney

Hydralazine- you can love or hate as a nephrologist. Hydralazine is used a lot for both inpatient and outpatient setting my several internists, cardiologists and nephrologists for management of blood pressure. In clinical practice, many times we have noticed vasculitis from hydralazine : both of the lupus or the ANCA kind. Drug induced kidney diseases are important to keep in mind when the clinical picture doesn't make any sense. 

See this exhaustive table from Izzedine and Ng in the recent Kidney News issue on drug induced glomerular diseases. 

A recent study in KI just focused on hydralazine induced ANCA vasculitis and looked at 80 patients.
As suspected, the clinical clues are: many have low complements, +ANCA( both p and c in some cases- 40%), ANA and anti histone positive and even dsDNA positive. When you see several auto antibodies come back positive- think drug induced. Treatment is cessation of the agent and treat like regular vasculitis. 

Check out an old detective nephron from 2013 on this topic.