HIGH-RESOLUTION ULTRASTRUCTURAL-STUDY OF THE RAT GLOMERULAR-BASEMENT-MEMBRANE IN AMINONUCLEOSIDE NEPHROSIS

In the initial stages of aminonucleoside nephrosis, functional alterat ions in the glomerular basement membrane occur, as evidenced by the de velopment of proteinuria. However, it has not been possible to observe important ultrastructural modifications at the level of the basement membrane, probably because the changes are taking place at the molecul ar level. In this study, by the use of high-resolution electron micros copy, an attempt was made to evaluate such changes in rat glomerular b asement membrane during acute aminonucleoside nephrosis. As previously reported, in control animals the glomerular basement membrane is comp osed of a network of 4-nm-wide irregular anastomosing strands, referre d to as ''cords,'' which are known to contain a core filament of type IV collagen surrounded by a ''sheath'' of other components, such as la minin and heparan sulfate proteoglycan (HSPG). The most conspicuous ul trastructural alteration of the nephrotic glomerular basement membrane , recognizable only at high magnification, is that the cords were denu ded leaving only the core filament through the loss of the sheath mate rial. Thus, the cord network was transformed, with the progress of pat hological conditions, into a network of fine filaments. On the other h and, abundance and distribution of HSPG molecules known to be present in the form of 4.5- to 5-nm-wide ribbon-like ''double tracks,'' were f ound to be similar in control and nephrotic tissues. Since HSPG is one of the charge proteins of the basement membrane, the little changes o bserved for HSPG are difficult to interpret in view of reported decrea ses in basement membrane anionic sites in nephrosis. In conclusion, th e glomerular basement membrane in aminonucleoside nephrosis loses its cord network components and replaces them with a more perforated netwo rk, which could be a cause for the increased permeability of this base ment membrane.