Lower Podocyte Number per Glomerulus Associates With Progressive CKD

Podocyte depletion may play an important role in chronic kidney disease (CKD); however, longitudinal clinical studies are lacking in populations without obesity-related glomerulopathy.

Patients studied underwent radical nephrectomy for tumors between 2000 and 2021 and had < 10% interstitial fibrosis and tubular atrophy (IFTA) on histology. Cases who developed progressive CKD were identified by the onset of dialysis, kidney transplantation, sustained estimated glomerular filtration rate (eGFR) < 10 ml/min per 1.73 m², or sustained 30% eGFR decline after the postnephrectomy baseline eGFR. Each case of progressive CKD was age-sex-matched to a control without progressive CKD at the same follow-up time. Podometric measures (number/glomerulus, density, and cell volume) and parietal epithelial cell (PEC) measures (number/glomerulus and density) were determined with immunohistochemistry and stereology. The risk of progressive CKD with podometric measures was assessed, adjusting for glomerular tuft volume, glomerulosclerosis, IFTA, and arteriosclerosis (all determined by morphometry) or adjusting for age, sex, diabetes mellitus, body mass index (BMI), hypertension, eGFR, and proteinuria.

There were 35 CKD cases and 35 controls studied. Cases versus controls did not differ significantly by BMI (mean: 29.1 vs. 28.2 kg/m², P = 0.88), glomerular tuft volume, or PEC number, but had lower podocyte number, lower podocyte density, and lower PEC density. Lower podocyte number correlated with several nephrosclerosis measures. In adjusted analyses, podocyte number and podocyte density associated with progressive CKD and these associations did not substantively differ by cortex depth.

Low podocyte number per glomerulus is associated with the development of progressive CKD independent of CKD risk factors, kidney function, glomerular volume, and nephrosclerosis severity.