NDT Advance Access originally published online on February 19, 2004
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Nephrol Dial Transplant (2004) 19: 1437-1440
Nephrol Dial Transplant Vol. 19 No. 6 © ERA-EDTA 2004; all rights reserved
Original Article
Structural alterations to the podocyte are related to proteinuria in type 2 diabetic patients
School of Clinical Medical Sciences, Medical School, University of Newcastle upon Tyne, UK
Correspondence and offprint requests to: Dr K. E. White, Clinical Medical Sciences, 4th Floor William Leech Building, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Email: k.e.white{at}ncl.ac.uk
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 106 µm3, 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)/106 µm3, 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.
Keywords: diabetic glomerulopathy; glomerular filtration barrier; podocyte number
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