Stenosis of the glomerulotubular neck in progressive chronic kidney disease.

Abstract

Morphology and morphometric evaluation of lesions beyond conventional parameters can inform the pathophysiology of chronic kidney disease (CKD). We sought to determine whether the occurrence of glomerulotubular neck stenoses associates with progressive CKD. We evaluated the normal parenchyma from radical nephrectomies removed for tumor between 2000 and 2021 and analyzed cortex for stenoses of the glomerulotubular neck. Stenosis of the glomerulotubular neck is defined a focal narrowing for which the draining tubule has a greater diameter than at the neck. Progressive CKD was defined as dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73m2 or sustained 40% decline from the post-nephrectomy eGFR. Each case of progressive CKD was age-sex-matched to 2 controls without progressive CKD. Logistic regression models assessed the risk of progressive CKD with stenotic necks adjusting for other histological features, kidney function, and CKD risk factors. There were 65 cases with a mean of 255 glomeruli and 130 controls with a mean of 329 glomeruli. Among both cases and controls, 5% of glomeruli showed visible glomerulotubular necks. The proportion of necks that were stenotic was higher in cases than controls (35% vs. 11%, p<0.0001). Stenotic necks associated with progressive CKD independent of other histologic and clinical characteristics. Glomerulotubular neck stenosis is associated with development of progressive CKD.