Monday, July 9, 2018

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.

Sunday, July 8, 2018

Topic Discussion: FGF-23- friend of foe?


FGF-23 has a been a molecule that has really starting changing the way we have thought of bone mineral disease in Nephrology. There have been some observational studies showing that higher the FGF-23 level, the worse the renal and cardiac outcomes in CKD and ESRD patients

Two studies I stumbled on twitter world shocked me. 
The first was the 2012 JCI paper that showed FGF-23 neutralization improves CKD-associated hyperparathyroidism yet increases mortality. While this was an animal study, it showed that reducing FGF-23 was not a good thing. To determine the role of FGF-23, and role on CKD-MBD and secondary hyperparathyroidism, the authors developed a monoclonal antibody against FGF-23 to evaluated the impact of chronic FGF-23 neutralization on CKD-MBD and associated morbidities in a rat model of CKD-MBD. CKD-MBD rates were fed a high phosphate diet and treated with low and high doses of the antibody or an isotype control of the antibody. Neutralization of FGF-23 led to reduction of PTH, increased vitamin D levels and calcium level and normalization of bone markers. But they also observed dose dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with the FGF-23-ab.
Interesting, the monoclonal antibody to FGF-23 has been now clinically used in X linked hypophosphatemia recently published in NEJM

The second study is a recent JASN meta-analysis of prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. The  increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggested that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.

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