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.

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?