Structural alterations to the podocyte are related to proteinuria in type 2 diabetic patients

Abstract

Background: The podocyte is believed to play a key role in maintaining the integrity of the glomerular filtration barrier, and damage or loss has been linked to the development of albuminuria.

Methods: Renal biopsies from 16 type 2 diabetic patients with nephropathy and 28 non-diabetic controls were analysed using light and electron microscopy.

Results: Podocyte number per glomerulus was significantly lower in the type 2 patients compared with controls [mean (95% confidence interval) 464 (382-546) vs 589 (543-635), P = 0.004]. Mean glomerular volume was significantly increased in diabetic patients compared with controls [5.5 (4.9-6.1) vs 3.1 (2.7-3.5) x 10(6) microm(3), P<0.001], thus the diabetic patients demonstrated an even greater proportional reduction in podocyte density per glomerulus [88 (68-108) vs 201 (182-220)/10(6) microm(3), P<0.001]. Podocyte foot process width on both the filtration surface (FPWgbm) and mesangial surface (FPWmes) was significantly increased compared with controls [796 (708-884) vs 556 (460-908) nm, P = 0.001; 1108 (821-1394) vs 760 (555-1078) nm, P = 0.029, respectively]. There was a significant negative correlation between proteinuria and both podocyte number and podocyte density per glomerulus (r = -0.63, P = 0.009; r = -0.58, P = 0.018, respectively). There was a significant positive correlation between proteinuria and both FPWgbm and FPWmes (r = 0.64, P = 0.008, for both).

Conclusion: Podocyte loss occurs in type 2 diabetic nephropathy and is related to increasing proteinuria. Whether the accompanying glomerular enlargement and widening of foot processes are a cause of podocyte loss is uncertain. Longitudinal studies are required to determine the sequence of events leading to podocyte loss in diabetic nephropathy.