Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft Failure

Abstract

BackgroundHistology can provide insight into the biology of renal allograft loss. However, studies are lacking that use quantitative morphometry to simultaneously assess changes in mean glomerular volume and in the percentages of globally sclerosed glomeruli (GSG) and ischemic-appearing glomeruli in surveillance biopsies over time to determine whether such changes are correlated with late graft failure.MethodsWe used digital scans of surveillance biopsies (at implantation and at 1 and 5 years after-transplantation) to morphometrically quantify glomerular volume and the percentages of GSG and ischemic-appearing glomeruli in a cohort of 835 kidney transplants. Cox proportional hazards models assessed the risk of allograft failure with these three glomerular features.ResultsFrom implantation to 5 years, mean glomerular volume increased by nearly 30% (from 2.8×106to 3.6×106µm3), mean percentage of GSG increased from 3.2% to 13.2%, and mean percentage of ischemic-appearing glomeruli increased from 0.8% to 9.5%. Higher percentages of GSG and ischemic-appearing glomeruli at five-year biopsy predicted allograft loss. The three glomerular features at five-year biopsy were related; the percentage of GSG and the percentage of ischemic glomeruli were positively correlated, and both were inversely correlated to glomerular volume. At 5 years, only 5.3% of biopsies had ≥40% ischemic glomeruli, but 45% of these grafts failed (versus 11.6% for <40% ischemic glomeruli). Higher Banff scores were more common with increasing percentages of GSG and ischemia, but at 5 years, only the percentage of ischemic glomeruli added to predictive models adjusted for Banff scores.ConclusionsGlomerular changes reflect important pathologic processes that predict graft loss. Measuring glomerular changes quantitatively on surveillance biopsies, especially the proportion of ischemic-appearing glomeruli, may enhance the current Banff system and be a useful surrogate end point for clinical intervention trials.

A nomogram based on contrast-enhanced ultrasound for evaluating the glomerulosclerosis rate in transplanted kidneys

“…Vaulet et al analyzed 3,549 tissue specimens from different time points after transplantation and observed that the time after transplantation correlated with the overall chronicity of the biopsy specimens ( 30 ). Denic et al reported that the mean percentage of glomerulosclerosis in patients with transplanted kidneys increased from 3.2% at implantation to 13.2% at 5 years after surgery ( 31 ). Another study demonstrated that the proportion of patients with a glomerulosclerosis rate >20% increased from 0% to 47% 10 years after transplantation ( 32 ).…”

Tubular and Glomerular Size by Cortex Depth as Predictor of Progressive CKD after Radical Nephrectomy for Tumor

“…31 These enlarged nephrons can eventually collapse and sclerose 32,33 and are associated with an increased risk of progressive CKD and kidney failure. 1–4,34–38 However, it is unclear whether this CKD risk differs depending on the hypertrophy of different segments or depths of nephrons. In this study, we found that glomerular enlargement was predictive of progressive CKD and kidney failure at middle and deep depths independent of tubular diameters and clinical characteristics.…”

Morphometric analysis of chronicity on kidney biopsy: a useful prognostic exercise

“…Among nephrotic syndrome patients, an increased risk of progressive CKD was only evident when the %GSG exceeded age-based thresholds for GSG [ 41 , 45 ]. Among kidney allografts at a 5-year surveillance biopsy, higher %GSG as well as higher % ischemic-appearing glomeruli were predictive of subsequent allograft loss [ 46 ].…”