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!

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

Concept Map: Methotrexate Renal Toxicity

 

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

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

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? 

Concept Map- Causes of Renal Amyloidosis

 

Created using biorender.com