Glomerular basement membrane length to podocyte ratio in human nephronopenia: implications for focal segmental glomerulosclerosis

Abstract

Background:This study aims to probe a possible mechanism for the development of focal segmental glomerulosclerosis (FSGS) in human nephronopenic states. Methods:To this end, length (in microns) of the glomerular basement membrane (GBM) covered by the cytoplasm of a podocyte was determined in controls and various congenital and acquired forms of nephronopenia with and without FSGS. Results:Results indicate that for all nephronopenic groups without FSGS, the respective lengths are not significantly different from those of controls. With the exception of long-surviving renal allografts with FSGS, each nephronopenic group with FSGS has a significantly longer length compared with its respective control group without FSGS. Although the corresponding length in long-surviving allografts with FSGS is longer than that in the transplant group without FSGS, the difference does not attain significance. Among all groups with FSGS, the respective GBM lengths are not significantly different among cases of congenital causes of nephronopenia, but are significantly longer than when nephronopenia is acquired, whereas the corresponding lengths among uninephrectomized and transplant groups are not significantly different from one another. Conclusion:These results support the hypothesis that in enlarging glomeruli of nephronopenia, the dominant reaction of podocytes is to undergo hypertrophy. The capacity for this is greater in podocytes of native kidneys than allografts, being most pronounced when the nephronopenia is congenital than if acquired, and being most constrained in allografts. This then imposes a limit to glomerular enlargement in nephronopenia beyond which denudation of segments of the enlarging/elongating glomerular capillaries occurs, when FSGS supervenes.