HDCN Article Review/Hyperlink

Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, Meyer T

Podocyte loss and progressive glomerular injury in type II diabetes

J Clin Invest (Jan) 99:342-348 1997

The occurrence of diabetes mellitus (type II) and consequent nephropathy in Pima Indians at an earlier age compared to other ethnic groups provides an opportunity to study renal morphologic abnormalities with little interference from age related changes.

In this study the authors biopsied 51 Pima Indians who belonged to four groups: early diabetes without albuminuria, long term diabetes without and with microalbuminuria, and clinical nephropathy. The control group consisted of eight non-Pima Indians who were kidney donors. There was a progressive increase in glomerular volume, fractional mesangial volume and GBM thickness compared to controls. The width of the foot processes increased in diabetic patients over time. The actual number of podocytes per glomerular tuft was decreased in patients with clinical nephropathy. However, the density of podocytes in the glomerualr tuft was progressively lower and the area occupied by the individual podocyte, podocyte volume and number of nonpodocyte cells per glomerular tuft were progressively higher with passage of time. The authors suggest that podocyte loss contributes to the progression of diabetic nephropathy.

Comment: This article addresses the role of podocyte in diabetic nephropathy, an area that has not received much attention in the past. It is conceivable that decrease in podocyte population results in stretching of the remaining cells as the glomerular volume expands. This act of stretching may cause important change in the cytoskeleton and affect the function of the cell, eg., synthesis of matrix components. A reduction in the actual number of cells per glomerulus would also raise the possibility of apoptosis as a mechanism of podocyte loss. The major issue of concern in this paper is the lack of appropriate controls. The morphometric parameters in Pima diabetics are compared to non-Pima Indian controls. It is known that in normal nondiabetic Pimas the glomerular volumes are twice that seen in whites (Schmidt K et al, J Amer Soc Nephrol 3:229, 1992). Schmidt and associates could not find any increase in glomerular volume in established diabetic nephropathy among Pima Indians (ibid). Therefore, it is unclear if a reduction in podocyte density actually occurs relative to controls. Additionally, the findings of decrease in podocyte density and loss of renal function is correlative. A cause and effect relationship remains to be shown. However, the paper has rekindled interest in potential role of the podocyte in diabetic nephropathy. (B.S. Kasinath, M.D., University of Texas at San Antonio)

The full text of this article is available from the JCI online site at this link .