Saturday, September 11, 2021

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)



Wednesday, August 11, 2021

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!

Thursday, July 29, 2021

Nephrology and US News and World Report Rankings

 

Traditionally, all fields in medicine had some sort of ranking in US News and World Report. July 2021, Nephrology was removed and was changed to rankings based on " Renal Failure".  What does that even mean?

Traditionally, what consists the score is patient experience, structure, mortality and length of stay and nephrology used to include reputation related to both med and surgical procedures. We don't know what the "kidney failure" consists of when the new rankings were assigned. 

Even the old way of ranking was flawed- as many of us know that when you include surgical procedures- you are not involving other fields like vascular surgery, transplant surgery and perhaps Urology. That is " Kidney care" but not " Nephrology". And " Kidney failure" alone is not nephrology either.

ASN President and ASN timely released a rebuttal and I think this needs to be read by all. This is extremely important. 

https://www.asn-online.org/about/press/releases/ASN_PR_20210727_Hospital_Rankings_S.pdf


The " Kidney Failure" is not a good way to advertise nephrology to patients as most patients see US News World report.  Nephrology is a field that includes quality care in Prevention, Treatment and then Management of AKI. In addition, other hospital acquired disorders such as acid base, hyponatremia and so forth are part of Nephrology. Complex GN cases are not easy to define treatment and are also part of nephrology. Social components are also critical when we discharged ESKD patients and obtaining an outpatient dialysis spot in certain parts of the country is not easy for patients. Lot of key stakeholders are involved in this and length of stay can get affected. 

As pointed out in the rebuttal by ASN, during the initial surge of COVID19 in 2020, many states experienced AKI and dialysis shortages-- how did we all manage this as a community- we can't prevent the AKI in some cases- but how did we manage it.. that is extremely important. As a field in medicine, we really excelled and did our best!

In general, rankings are not good in certain fields that are more as a result of other fields like Nephrology. What I mean is - our AKI cases in general are NOT caused by us- they are either drug induced, sepsis induced, ct surgery induced, contrast induced, etc... So how can the field of Nephrology be responsible for this or the respective program in that hospital. It really is a more complex and more large system issue that needs more collaboration and dedication from other fields in medicine to PREVENT AKI and associated complications. Intrinsic renal causes such as GNs or TMA are a rare entity in a large scheme of things.

In another editorial, the authors say that it is about time we stop ranking hospitals based on their reputation mainly but look at the crucial layers of data within the state. The author suggests that look at the areas in which a hospital performs , measure each of them and give a score set- simple- remove the reputation component and keep it fair.

Perhaps the ranking systems needs consultants to guide them from both academic and community nephrology to help create a rank list -if we still even want to do that. I say we bow out and just focus on providing good care!

Kudos to ASN for saying what is on our mind

Tuesday, July 20, 2021

Concept Map: Methotrexate Renal Toxicity

 


Picture created using biorender.com
Pathology pic obtained from google: Arkana lab collection. 

Sunday, July 4, 2021

ASN Kidney News All Education Issue 2021

 July 2021 is an entire issue of ASN Kidney News. See all visual abstracts related to the issue



















Saturday, July 3, 2021

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



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. 



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? 

Thursday, June 3, 2021

Immune checkpoint inhibitors and the Kidney infographic

 


Here is a comprehensive infographic by Tejas Desai on 4 studies from around the world with ICI and the Kidney. 

Sunday, May 30, 2021

Topic Discussion: SGLT2i and the Kidney

 


Two tweetorials I had recently done on the benefits of SGLT2 inhibitors

Here is a table summary of what exists on benefits of various things in Nephrology


SGLT2i  benefit

Summary or Major Reference

Diabetic Kidney Disease

https://onlinelibrary.wiley.com/doi/full/10.1002/clc.23508

 

IgA Nephropathy

https://www.kidney-international.org/article/S0085-2538(21)00396-3/fulltext

 

SIADH

https://jasn.asnjournals.org/content/31/3/615.abstract

 

Hypomagnesemia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380494/

 

Kidney Stones Prevention

https://link.springer.com/article/10.1007/s00125-021-05424-4

 

Anemia of CKD

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30300-4/fulltext

 

Prevent AKI

https://cjasn.asnjournals.org/content/16/1/70.abstract

 

Prevention of cisplatin AKI

https://journals.physiology.org/doi/full/10.1152/ajprenal.00512.2019

 

 

Monday, May 17, 2021

COVID19 vaccine induced glomerular diseases?- a literature update May 2021

The vaccine for COVID19 has been a lifesaver for many around the world. As expected, as you upregulate your immune system- you are going to get some flare ups of your immune system. Thus far, what are we noticing Minimal change disease, MN and IgA nephropathy. 

Several published cases of podocytopathies- mainly minimal change disease- either de-novo or relapse have been reported ( 4 cases thus far)

https://www.kidney-international.org/article/S0085-2538(21)00493-2/fulltext (Pfizer-BioNTech )

https://www.sciencedirect.com/science/article/pii/S0272638621005096 (Pfizer-BioNTech) 

https://www.ajkd.org/article/S0272-6386(21)00602-8/fulltext ( Pfizer-BioNTech )

https://www.kidney-international.org/article/S0085-2538(21)00478-6/fulltext (Pfizer-BioNTech)

IgA nephropathy flaring up has been reported ( 3 cases thus far)

https://www.kidney-international.org/article/S0085-2538(21)00465-8/fulltext ( Moderna)

https://www.kidney-international.org/article/S0085-2538(21)00286-6/fulltext (Moderna)

Relapse of Membranous Nephropathy  ( one case)

https://www.kidney-international.org/article/S0085-2538(21)00494-4/fulltext (Sinovac’s COVID-19 vaccine.)

Acute transplant rejection has been reported

https://www.kidney-international.org/article/S0085-2538(21)00466-X/fulltext Pfizer-BioNTech)

While we cannot be totally sure if this is vaccine related- timing maybe a factor. I am sure there will be many more to be added to this list.

Despite this, the vaccine saves lives! Remember severe COVID19 disease led to significant AKI and ATN and even several cases of glomerular diseases. Such vaccine associated immune responses should not deter one from getting vaccinated. Overall, even the flu vaccine and other vaccines have been associated with several glomerular diseases such as MCD and membranous nephropathy.  Given mass vaccinations happening around the world, there will be cases of vaccine induced GNs( but still very very rare)

Detective Nephron: Next venture


 

https://www.kidneynews.org/view/journals/kidney-news/13/5/article-p12_4.xml


Wednesday, April 21, 2021

Concept Map: Infections and Renal Transplant

 


Figure made using biorender.com 

Hypophosphatemia with anti-cancer agents

 


Here is a schematic of what we know for now in 2021 in relation to anti cancer agents leading to low phosphorus. This was made using biorender.com and inspired by the article Adhikari et al

Wednesday, April 14, 2021

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.

Saturday, March 20, 2021

Topic Discussion: Electrolytes Disorders with COVID19

AKI has been reported with COVID19 ,electrolyte disorders have been less well described. A recent paper in CKJ describe the full spectrum of electrolyte disorders seen with COVID19.

The most common presentation was hyponatremia and hypochloremia together (second vertical bar) in 1289 (12.4%), followed by hyponatremia alone (third vertical bar) in 1150 (11.1%).




What about patients with eGFR<60 but >15? 30.3% had hyponatremia, 11.1% had hyperkalemia, and 19.7% had hypochloremia. Hypocalcemia was seen in 19.2% of patients. Hyperphosphatemia (13.9%) and hypermagnesemia (12.2%) were seen in fewer patients.

What about ESKD patients?
In these patients the most common disorders were hypochloremia (62%), hyponatremia (40.9%), and hyperkalemia (23.4%). Hyperphosphatemia was seen in 45.7% of patients but we had some missing phosphorus data.

What about kidney transplant recipients? The most commonly seen were hyponatremia (42.4%), hyperkalemia (16.7%), and hypochloremia (19%).

Limitations: Purely descriptive.
But highlights for the first time and the largest to date on the various electrolyte disorders in hospitalized COVID-19 patients. Further studies are needed to look at mortality outcomes related specifically to each electrolyte disorder.

Prevalence of Hyponatremia related to COVID19 has been described in the NY region. Looking at the spectrum of both hyponatremia and hypernatremia and it's relation to patient outcomes has not been well studied.

To take this further, Na disorders were evaluated in detail with outcome of mortality. This is published in NDT. Among 9946 patients included in the study ,4808 (48.3%) had normonatremia, 3532 (35.5%) had mild hyponatremia, 904 (9.1%) had moderate/severe hyponatremia, 319 (3.2%) had mild hypernatremia, and 383 (3.8%) had moderate/severe hypernatremia. When examined by decile of age, dysnatremia occurred in 46-54% of patients in each group, with hyponatremia the predominant disorder across all age groups. The proportion of patients who experienced in-hospital death was highest for those with moderate/severe hypernatremia (232/383 [60.6%]), followed by mild hypernatremia (163/319 [51.1%]), moderate/severe hyponatremia (261/904 [28.9%]), mild hyponatremia (818/3532 [23.2%]) and normonatremia (1089/4808 [22.6%]), a trend seen across all age groups. 




U-shaped pattern was seen in the relationship between admission serum sodium level and the odds of in-hospital death, with hyponatremia and hypernatremia both significantly associated with mortality, even after full adjustment for demographics, comorbid conditions and illness severity. Compared to hyponatremia, hypernatremia carried a strong association with in-hospital death, in both mild and moderate/severe categories, and across all ages, a relationship that persisted even following correction for serum glucose. While hypernatremia has  been shown to be  a strong predictor of mortality in prior studies, this finding is novel for COVID-19. 




Both hyponatremia and hypernatremia were also associated with a prolonged hospital length of stay. The magnitude of the odds ratio was substantial, especially for moderate/severe hypo- and hypernatremia, and was not substantively changed after multivariable adjustment. This suggests that at least a portion of the prolonged hospitalization may be directly related to electrolyte disorder management. 

This is the largest study to describe prevalence and outcomes of both hyponatremia and hypernatremia in a diverse population of almost 10,000 patients hospitalized with COVID-19. Other similar studies just published in the endocrine literature as well.

Concept Map: Anorexia Nervosa and the Kidney

 


Sunday, March 14, 2021

Topic Discussion: Chloride in Cardio-Renal Syndrome



At recent ASN Kidney Week 2020, Dr. Amir Kazory really gave a great lecture highlighting the importance of an important ion that often is ignored in CHF and Cardio-renal syndrome.

We should perhaps move away from the Na centric view of CHF.

Some interesting points made in his talk and overall what we know.

1. Hyponatremia is a predictor of CHF outcomes. But when we correct the Na, mortality doesn't improve. - classic V2R antagonist EVEREST trial showed no benefit

2. When we give 3% saline as shown by the Yale group recently in JACC, there is significant weight loss in diuretic resistant patients. 

3. The Na restriction in diet has limited evidence that it works


Some interesting data on Cl in CHF.

One of the first studies done looking at Cl in CHF found that for every 4.1meq/L of drop in Cl, there is 25-30% increase in 5 year-mortality. 


Contemporary advanced CHF cohort suggest that serum chloride levels at admission are independently and inversely associated with mortality in this one study. The prognostic value of serum sodium in CHF was diminished compared with chloride.



Why does this matter? 
Two physiological reasons:

1. Low Chloride can stimulate renin release in macula densa

2. Low intracellular chloride can increase TAL NKCC activity and DCT NCC activity




Interestingly, low chloride patients are also diuretic resistant. 

It would be fascinating to see if increasing Cl, without Na really has a good effect on diuresis. Azetazolamide trials are ongoing as a potential way to do this. Could SLGT2i be potentially working via this mechanism? It is very possible that Cl is a more important player than Na in CHF and Cardio-renal syndrome. Fascinating!!

Check out this excellent review. ( also for figure source)





Saturday, March 6, 2021

IN the News: Pediatric AKI related with COVID19 and MISC- tale of two NY centers

 


A recent study published in Kidney International looked at a single health system 4 hospital admissions of AKI with COVID19 and MISC in children in NY. It was during the first wave in 2020.  

Over 150 patients met inclusion criteria; 97 (63.8%) with acute-COVID-19 and 55 (36.2%) with MIS-C, AKI occurred in 11.8% of the cohort; 8 with acute-COVID-19 and 10 with MIS-C.  All but one patient with AKI were admitted to a pediatric intensive care unit (PICU). There was no significant difference in age, or ethnicity in those with and without AKI. Those who identified as black had 2.86 times higher odds of AKI (p=0.042; 95%CI 1.04-7.93). 

Majority of AKI occurred early in the course of hospitalization, 72% (N=13) within 24 hours of admission. MIS-C patients with AKI had greater rates of systolic dysfunction, compared to those without AKI (80% vs 49%, p= 0.038).  AKI, in unadjusted models, was associated with a lower serum albumin level (OR 0.17)and higher white blood cell counts (OR 1.11). In addition, patients with AKI had 8.4 day greater length of stay. Major Limitations: 1. Small sample size precluded adjustment for confounders 2. As this was an observational study, we are unable to determine causal associations. 3. Single health system/region of the country
Strengths of this study: One of the largest, detailed cohorts of pediatric patients at the epicenter of the COVID-19 outbreak and represents a diverse racial, ethnic and socioeconomic population.

Similar to reports in other PICU patients, pediatric COVID-19-related AKI was associated with longer lengths of stay published in Kidney360 also from NY area. In that study, 57 children who met inclusion criteria, 46% (26/57) were found to have AKI.  All patients had resolution of AKI at discharge, with 61% achieving recovery by day 2. One patient required dialysis. When compared to those without renal injury, the AKI cohort was older (p < 0.001) and with higher median peak values of CRP (p <0.001), IL-6 (p <0.05), ferritin (p < 0.001), and procalcitonin (p <0.05). More patients with AKI had left ventricular systolic dysfunction (p < 0.001) and lymphopenia (p <0.01), when compared to those without AKI. No differences in Body Mass Index or sex were found. 

These findings may reflect the inflammatory cascade’s complex role in development and perpetuation of COVID-19 related AKI. In addition, decreased intravascular volume and distributive/cardiogenic shock may have contributed to AKI in the MIS-C cohort. 

Check out the tweetorial by Abby Baselely 

Friday, February 19, 2021

Warp Speed Drugs for Kidney diseases 2021

 In ASN Kidney News 2021, Feb issue, I created this figure that gives a sense of the amazing rapid development for kidney disease therapeutics. The figure appears in the Feb issue of kidney news. Created using biorender.com 




Sunday, February 14, 2021

Topic Discussion: ACEI/ARB ( hold em or keep them going)

 The COVID19 pandemic has ignited an ongoing saga of holding ACEi/ARB when someone is hospitalized. Normally a consult note in nephrology would include holding of these agents before a cardiac cath, CABG, or major procedure ( with little data on doing it).

A recent study in JASN done using a novel methodology showed no real benefit in stopping these agents in late stage CKD patients in the Swedish Renal Registry for the last 10 years.  Advanced CKD ( GFR<30) on these agents were evaluated. A target trial emulsion technique was used on risk of stopping these agents for 6 months and their outcomes on 5 year mortality, and MACE and KRT. So while KRT risk increased, the MACE and mortality decreased. MACE was mainly driven by mortality. In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.


Meanwhile, in the COVID19 world,  REPLACE COVID published in Lancet was published. T
his trial began on March 31, 2020, within a few months of COVID-19 hitting North America and in the thick of the first wave. All COVID19 patients hospitalized , already on chronic ACEi or ARB  were randomized to either continue or stop their ACEi or ARB. In terms of the results, there was absolutely no difference in any of the outcomes, all cause death and length of stay. There was also no difference in the exploratory outcomes of ICU admission, ventilation, or hypotension requiring hemodynamics support. These findings are also bolstered by the similar findings from the BRACE CORONA trial published in JAMA in a slightly less sick cohort of 659 patients showing similar results. The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.  The study found that in patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These two trial (RCTs done in pandemic)  findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with COVID19.  Check out this nice editorial on this in ASN kidney news 2021

There is an ongoing trial called STOP-ACEi. Do we really need that trial? Given we were able to do an RCT in a middle of a pandemic with sick patients with COVID19 and that showed no real difference in terms of outcomes of holding ACEi or ARBs, my guess is that STOP-ACEi will show the same. Unless there is hyperkalemia, or hypotension, no real strong indication to hold or stop these life saving cardiac medications.

Culture change will take time:  It is hard to convince nephrologists to start ACEi/ARB in late stage CKD, let alone convincing hospitalists or internists. It is hard to NOT to hold ACEi/ARB when creatinine is rising during an acute cardio-renal syndrome- convincing will take time. Hope these trials will help us continue these life saving agents in hospitalized patients( and ok to even stop them) but sometimes- nobody restarts them on discharge... 



Thursday, January 28, 2021

Discussion via pics: Bile Cast Nephropathy

 


Image made via biorender.com
Images in that obtained from:

https://www.kidney-international.org/article/S0085-2538(15)55928-0/fulltext
https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-020-00265-https://laboratoryinfo.com/types-of-crystals-in-urine/

Saturday, January 9, 2021

Topic Discussion: Acute Peritoneal Dialysis during COVID-19

 As the NYC area had seen surge of cases in all health systems in March, April, May 2020, need for creative solutions to do dialysis was essential. NYU and Weill Cornell in NYC were two centers that really pioneered this method during the COVID-19 pandemic. 

This manuscript published in Kidney360 highlights 39 acute catheter placements and use of PD in the acute setting. Almost 40% even had recovery of AKI. 












Here is the Cornell data of 11 patients published in KI reports, 6 patients recovered.


Two concerns that most would have is:

1. Entering the rooms to do cycler and exchanges.
2. Can PD be done in prone ventilation as proning helped COVID19 patients recover?

See this picture from the NYU series

The figure shows placement of the cycler outside the ICU room and using longer connectors. Drain bags were used to obliviate use of drain line. The room was also HEFA filtered for airborne isolation.


Another series of patients in NYU was published in PD International on how they were able to do successful PD in vented patients with proning. Although the mortality was 100%, the venting was not effected and relative clearance was good. 

Perhaps, the silver lining of COVID19 related AKI-- return of Acute PD...


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