AJP - Renal Physiology, Vol 260, Issue 5 728-F737, Copyright © 1991 by American Physiological Society
Glomerular dysfunction in nephrotic humans with minimal changes or focal glomerulosclerosis
A. Guasch, H. Hashimoto, R. K. Sibley, W. M. Deen and B. D. Myers
Department of Medicine, Stanford University Medical Center, California 94305.
Fractional clearances (theta) of uncharged dextrans (radii 28-60 A) were
used to characterize glomerular dysfunction in 34 nephrotic humans with
either minimal-change nephropathy (MCN) or focal, segmental
glomerulosclerosis (FSGS). A theoretical analysis of theta of dextran with
a heteroporous membrane model revealed a similar alteration, more marked in
FSGS than MCN. The number of restrictive pores perforating the major
membrane component was reduced in parallel with the prevailing glomerular
filtration rate (GFR). Parallel shuntlike pores in the remaining membrane
component were more prominent, pointing to impaired size selectivity.
However, the theta of large (60 A) dextrans attributable to these shunts
exceeded control in FSGS only, suggesting that coexistent impairment of
charge selectivity contributed importantly to the proteinuria in MCN.
Membrane properties returned toward normal when MCN remitted. Glomerular
morphometry revealed the frequency of epithelial filtration slits to vary
with the extent of membrane dysfunction. Despite offsetting hypertrophy of
remnant glomeruli in FSGS, a loss of filtration surface due to sclerosis
likely contributed to the more marked reductions in pore number and GFR
observed in this disorder than in MCN.
