The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis Jingyuan Xie et al. # Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1

Background and objectives Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial.Design, setting, participants, & measurements We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys).Results For kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (k=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (k=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (k=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (k=0.13) and 80% (k=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure. ConclusionsWe found that procurement biopsies are poorly reproducible, do not correlate well with paraffinembedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

Background and objectivesUnfavorable histology on procurement biopsies is the most common reason for deceased donor kidney discard. We sought to assess the reproducibility of procurement biopsy findings.Design, setting, participants, & measurementsWe compiled a continuous cohort of deceased donor kidneys transplanted at our institution from 1/1/2006 to 12/31/2016 that had at least one procurement biopsy performed, and excluded cases with missing biopsy reports and those used in multiorgan transplants. Suboptimal histology was defined as the presence of advanced sclerosis in greater than or equal to one biopsy compartment (glomeruli, tubules/interstitium, vessels). We calculated κ coefficients to assess agreement in optimal versus suboptimal classification between sequential biopsy reports for kidneys that underwent multiple procurement biopsies and used time-to-event analysis to evaluate the association between first versus second biopsies and patient and allograft survival.ResultsOf the 1011 kidneys included in our cohort, 606 (60%) had multiple procurement biopsies; 98% had first biopsy performed at another organ procurement organization and their second biopsy performed locally. Categorical agreement was highest for vascular disease (κ=0.17) followed by interstitial fibrosis and tubular atrophy (κ=0.12) and glomerulosclerosis (κ=0.12). Overall histologic agreement (optimal versus suboptimal) was κ=0.15. First biopsy histology had no association with allograft survival in unadjusted or adjusted analyses. However, second biopsy optimal histology was associated with a higher probability of death-censored allograft survival, even after adjusting for donor and recipient factors (adjusted hazard ratio, 0.50; 95% confidence interval, 0.34 to 0.75; P=0.001).ConclusionsDeceased donor kidneys that underwent multiple procurement biopsies often displayed substantial differences in histologic categorization in sequential biopsies, and there was no association between first biopsy findings and post-transplant outcomes.

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Klok et al. [1] provide important insight into the coagulopathy that complicates COVID 19. They report an alarmingly high number of thrombotic complications (combination venous and arterial thromboembolism) in critically ill patients with COVID 19. They note an overall incidence of 31% composite outcome, much higher than the rate of thrombotic complications in prior series of critically ill patients prior to the COVID-19 pandemic [2]. Some clarification would be appreciated about how the 31% rate of the composite events was derived. Their study included 184 patients and a total of 31 events (25 PE, 3 DVT, 3 ischemic stroke). This seems to come to an incidence of 17% (95% CI 11-22). While still elevated, this is somewhat nearer to the upper end of rate of VTE in prior studies [2].Additionally, they noted an incidence of DVT that was only 1.6% (albeit without screening) while the majority of their outcomes were due to pulmonary embolism. Given that the authors are experienced in the diagnosis of VTE and encountered a disease that presents with marked hypoxia, I wonder if they had a lower threshold to obtain a contrast-enhanced scan, resulting in a higher than usual number of CT angiograms performed than would be typical in the critical care setting. It is quite possible that were as many CT angiograms performed on general critically ill patients that a similar proportion would be found to have pulmonary embolism, as was found by Minet et al. when all thoracic CTs obtained were performed with contrast enhancement -19% in their series [3].

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