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.
School of Clinical Medical Studies, Medical School, University of Newcastle upon Tyne, NE2 4HH, UK. k.e.white@ncl.ac.uk
Kathryn E
KE
White
Rudolf W
RW
Bilous
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*