Topic Discussion: COVID and Kidneys- the biopsy experience

As we expand our understanding of COVID-19 related AKI, in the last few weeks, more studies are emerging on what might be the main kidney biopsy findings with COVID related AKI.
We have now established the incidence being around 30-40% in the US.

What is exactly going on in the kidney? Is the virus attacking the kidney or is the renal disease a consequence of "being sick" and or  "inflammatory state".

This figure from an article in JASN summarizes the potential way the SARS-Cov2 might be effecting the kidney



Two recent biopsy series from Columbia and Northwell Nephrology showed the variety of pathology reported in COVID-19



In addition, an autopsy series (specific) to the kidneys showed ATN only.  Finally, in KI, a series of anti GBM were reported in UK related to COVID-19

All recent papers added interesting few things to the ongoing literature.

1. ATN is by far the most common presentation for AKI( if not pre renal)- even in transplanted kidney. Pigment nephropathy from myoglobin or hemoglobin is rare. Vitamin C overdose induced oxalate nephropathy is rare.
2. Podocytopathies( MCD and cGN) are the most common glomerular findings
3. Other glomerular diseases are a varied amount( TMA, ANCA, Membranous GN, anti GBM)
4. The virus was not found in the kidney with immunohistochemistry in all 3 studies.

Does the kidney get infected?- time will tell.. data is mixed

In the News: Kidney biopsies ( Nephrologists vs Radiologists)

An important study looked at kidney biopsy metrics and adequacy that might be important for the Nephrology world.

To understand adequacy and variation of kidney biopsies done by nephrologists and radiologist, the investigators collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. In summary, proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in this large study  were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to onsite division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained

a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086).

This is the by far the largest data analysis that could provide useful feedback and/or benchmark data to kidney biopsy proceduralists. It also provides objective data on the critical role of on-site evaluation and division

of tissue for obtaining adequate biopsy tissue appropriately divided for LM, IF, and EM. As treating nephrologists, we feel this is important and can make a major difference in diagnosis and treatment.

Interestingly, in this study, for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining a greater calculated amount of cortex for LM. Despite the trend for radiologist obtaining more tissue in general, biopsies from nephrologists had a greater percentage of cortex and were more likely to be considered adequate for LM. Why is that? Cortex obtaining is critical and getting that sample is importantly taught to us as fellows and attendings doing kidney biopsies. If my differential is AIN and ATN, then the cortex-medulla might not make a big difference but for a GN diagnosis, getting a cortex and having enough sample for LM, IF and EM is critical. 

In this study, the radiologists’ inadequate for LM rates for native kidney biopsies appeared be independent of on-site evaluation and authors suggest that this could be due to patient selection (with more challenging biopsies sent to radiology), could represent a long-term effect of lack of on-site evaluation, division, and feedback from pathologists, and/

or may be due to other factors.  Sonogram assisted vs CT scan guided was not discussed in this study.

This is an important study and a reminder to the Nephrology world to continuing doing kidney biopsies as nephrologists. It is critical to get adequate samples and nephrologists do a better job at that. Having onsite evals of adequacy also allows for this to be better. Educating the radiologists on this important topic is also critical if Nephrologists are not going to be performing this procedure anymore in near future. An article in a high index radiology journal is much needed to raise this important issue.

Kidney biopsies, we are at crossroads in Nephrology

The kidney biopsy has been a procedure that has been lived under Nephrology for years. Slowly and surely, nephrologists are being pulled in many different directions- dialysis patients, CKD patients , urgent K related consults and leaving the procedures behind to other specialties such as vascular for access placement and interventional radiology for kidney biopsies. 

A survey done nationally in 2014 hinted towards a downward trend of procedures done by Nephrology fellows. A more recent CJASN paper surveyed a single center graduating fellows and training program directors nationally on trends on kidney biopsies of renal fellows.

In reality, most private practicing nephrologists don’t perform their own biopsies. Radiologists have taken on that realm. Few academic nephrologists still perform biopsies along with fellows. When the graduates were asked the biggest barriers from doing their own kidney biopsies, they cited
1. System based logistics, and 2.time as the two most common factors.  One commented: “Doing only one would … wipe out 1/2 day of clinic … I can fill out and fax a request in 5 minutes …” Another: “The main reason (we) stopped was efficiency—(we) were at the mercy of the ultrasound suite.” Logistics require that the nephrologist coordinate access to an interventional suite with nursing support, conscious sedation, specialized equipment, and the necessary intra- and postprocedure monitoring.  Moreover, the 2017 Medicare national average physician reimbursement for kidney biopsy (CPT code 50200) was only US $135. Other concerns included skill loss when numbers dip under ten/year.  
Interestingly, more biopsies were performed when “IR” would do it rather than “nephrologist” due to time constraints. 

Program directors said the same thing. The most common barriers to achieving fellow competence were the same faced by our graduates: time (45%) and logistics (45%). Other commonly cited barriers were that graduates were unlikely to perform biopsies (41%), and faculty unwillingness to supervise (30%). High-volume programs (>100 biopsies/year, 15 of 74 programs) are likely to have dedicated facilities, equipment, and faculty—their systems allow logistic and time efficiency. Also, many junior faculty don’t feel comfortable supervising and the skill is being lost eventually.

The debate continues as we are deciding between “pragmatism” vs “ needed education”. As most graduates don’t use the skill of a kidney biopsy, should we abandon that procedure to be required in training of renal fellows. Is it required for fellows to know how to do the kidney biopsy? A rich debate has spurred about this topic on twitter and some are “for” and some are “against” keeping renal biopsies as requirements. 

A mid way approach: 

1.       Few specialized interested nephrologists maintain the skill per institution and teach interested fellows and it be only an elective requirement in our field.  There might be institutions where no nephrologist is interested in doing these and radiologist do all the biopsies.

2.       Rather than learning the actual procedure of “using the biopsy gun”, the fellows focus on indications, how to do the procedure, watch 5 procedures and log them and have a working knowledge of complications associated with the procedure. It is also important that the specimen received is cortex as often when not done by nephrologist- medulla is obtained. The procedure perform physician has to be explained to get more cortex especially when evaluating for glomerular diseases.

3.       Robust nephropathology education is required to supplement this on how the specimen is collected,  and cut and eventually reviewing pathology findings at each institution

While utterly disappointing, we are at crossroads in nephrology where we are losing procedures. Access placement is downtrending and now it is the kidney biopsies. We can get angry or frustrated or disappointed but this is the reality.  Data don’t lie!

We should be pragmatic and as mentioned in recent kidneycon 2018 guest speaker Jeff Amerine said –think about our customers- the patients and the fellows when designing our teaching product( lean canvas model approach).  The safety of patients matter- who can do it safely and with experience should be doing the procedure.  Our fellow market recipients are mostly not interested in learning kidney biopsy skills as most won’t use that skill in clinical practice.

A nice editorial by Scott Gilbert also was recently e published in CJASN.                

TOPIC DISCUSSION: Urinary Snapshot of Lupus Nephritis does not equal what you see on the Kidney Biopsy

What degree of Class IV lupus nephritis presents with just hematuria?

What degree of Class I lupus nephritis presents with just hematuria?

Take a look at this data from a recent paper in 2009 by Seshan et al.

Of 541 patients studied for classification of lupus nephritis,

40% of Class I, 19% of Class II, 22% of Class III, 4% of Class IV and 6% of Class V presented with asymptomatic hematuria.

40% of Class I, 42% of Class II, 25% of Class III, 7% of Class IV and 13% of Class V present with asymptomatic proteinuria

20% of Class I, 15% of Class II, 17% of Class III, 40% class IV and 65% of Class V presented with Nephrotic Syndrome.

20% of Class II, 34% of Class III, 27% of Class IV and 7% of Class V presented with Nephritic Syndrome

4% of Class II, 2% of Class III, 18% of Class IV and 2% of Class V presented with Acute renal failure

4% of Class IV and 8% of Class V had presented with Chronic renal injury.

So in summary: Lupus can present on kidney biopsy much more differently than clinically.  Look at the wide spectrum of just hematuria and proteinuria.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/19195967