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


CONCLUSIONS
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.
White
Kathryn E
KE
School of Clinical Medical Studies, Medical School, University of Newcastle upon Tyne, NE2 4HH, UK. k.e.white@ncl.ac.uk
Bilous
Rudolf W
RW
D000328:Adult; D001485:Basement Membrane; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000473:pathology*