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

Abstract

Background: Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. Methods: We studied patients who underwent a radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval shaped tubular profiles and estimated glomerular volume with the Weibel Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazards models assessed the risk of progressive CKD (dialysis, kidney transplantation, eGFR <10 ml/min/1.73m2, or a 40% decline from the post-nephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, post-nephrectomy baseline eGFR, and proteinuria). Results: Among 1367 patients were 133 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in superficial than deep cortex, even in adjusted analysis. Conclusions: Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas wider more superficial distal tubular diameters are an independent predictor of progressive CKD.

Authors' Reply: Morphometric Approach to Different Nephron Segments

“…Sasaki and Tsuboi for their thoughtful Letter to the Editor regarding our recent publication on a morphometric approach to analyze the size of different nephron segments. 1 We agree that this approach has the potential to help us understand how different medications may affect the human kidney. Specifically, this approach can be used to study the association between various medications and the size of different nephron segments.…”

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