Proteinuria and the Fragility of Normal and Diseased Glomerular Basement Membrane 1

Abstract

Summary

Single straight capillary strands measuring 60-100 μm were secured by micromanipulators and microprobes from excised peripheral portions of the tufts of isolated glomeruli. The physical properties of these strands were considered to represent those of GBM. Normal glomerular strands could be stretched up to 40% beyond their initial length with good recoil but broke when they were stretched from 60 to 77% beyond their initial length. By contrast 100% of the glomerular strands from the kidneys with AMN, 87% of those from kidneys with NTN and the most affected glomeruli from aged rats with glomerulosclerosis broke immediately when stretched beyond their initial length. Elasticity could not be determined under these circumstances. Normal glomerular strands showed marked increases in fragility when briefly exposed to proteolytic enzymes, neuraminidase, to polycations and to basic amines. It seems that direct enzymatic action on GBM or alterations in its chemical composition and molecular configuration as well as a reduction in its net negative charge can bring about striking changes in its fragility. These changes appear to be intimately associated with increased permeability. They appear with the onset of proteinuria in AMN and NTN and they return to near normal when the output of urinary protein returns to normal. It is suggested that the approximation of foot processes which commonly accompanies proteinuric states is a response on the part of the visceral epithelial cell to the instability and displacement of the foot processes and in particular of the delicate slit diaphragms occasioned by an underlying increasingly fragile BM. It is also suggested that the vasoactive amines not only lead to disjunction of endothelial cells but render the capillary or venular BM increasingly fragile and permeable.