Glomerular permeability: ultrastructural quantitative studies relating proteinuria to pathologic features in murine lupus nephritis

Abstract

The pathogenesis of proteinuria associated with immune complex disease is incompletely understood. A quantitative electron-microscopic study was undertaken to determine the relative contribution of lesions in capillary loops and mesangial basement membrane areas and their possible correlations to urinary protein excretion data. Pathologic features including the loss of foot processes (and slit diaphragms), the formation of junctional complexes in visceral epithelium, and the distribution of immune complexes in basement membrane were assessed in glomeruli of mice with lupus nephritis. Swiss albino mice served as control animals. In control animals the distribution of split pores per unit length of basement membrane was approximately 60% higher in capillary loop compared to mesangial basement membrane areas. In mice with lupus nephritis, the reduction in the number of slit pores per unit length of basement membrane to 30% or less of normal, the formation of epithelial junctions, and the relative distribution of immune complexes were not statistically different in capillary versus mesangial basement membrane areas. Animals with murine lupus showed poorly selective proteinuria, but the correlation between features studied and extent of protein excretion was poor. The results of these studies 1) establish the relative distribution of slit pores in mesangial and peripheral loop basement membrane, 2) demonstrate that glomerular changes associated with immune complex deposition are comparable in capillary and mesangial basement membrane areas, and 3) are consistent with a focal and nonuniform alteration in glomerular permeability properties associated with immune complex disease.