New Insights into the Pathogenesis of Minimal Change Disease

Abstract

The cause or causes of MCD remain unknown. Although recent work has suggested roles for various portions of the glomerular capillary filter and soluble mediators acting on the filter, many findings are inconsistently observed, have not been confirmed, or are not causal, but rather present only as a consequence of the nephrotic state. Some findings are reproducible, however, and may provide the greatest likelihood of providing new insights in the future. The visceral epithelial layer of the glomerular capillary filter is altered morphologically in nephrotic states in humans and in animal models like PAN-induced nephrosis. Such changes are presumably accompanied by changes in the cell surface and/or metabolism, and are reversible as shown in animal studies (Seiler et al, 1977) and temporally related to the onset of proteinuria (Blau and Michael, 1972). The importance of visceral epithelial integrity is further supported by the fact that disruption, elevation and death of visceral epithelial cells is a proximate event in the development of sclerosis of glomerular segments.

The visceral epithelium resides in a locus which is separated from the vascular compartment by the glomerular capillary wall where interaction with other cells is limited. It is highly probable that mechanisms for control of these cells depend in part on factors that traverse that glomerular capillary. The rapid development of recurrences of the nephrotic syndrome in children after the onset of respiratory infection suggests to us that a ’cellular effect’ plays a dominant role in this disease, rather than a change in fixed basement membrane components. The well recognized electron microscopic changes in the visceral epithelium—once thought to be a consequence of proteinuria—may in fact reflect a primary injury induced by a filterable circulating component. The recognition of Iymphohaemopoietic antigens on the visceral epithelium that appear at specific stages of ontogenesis (Platt et al, 1983) suggests to us that communication may exist between these cells and components of Iymphohaemopoietic system. Knowledge of the nature of this factor(s) and its putative derivation from Iymphohaemopoietic or other cells will, we believe, lead to a more complete understanding of this disease.