Outcome of the acute glomerular injury in proliferative lupus nephritis.

Abstract

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius > 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

Charge selectivity of the glomerular filtration barrier in healthy and nephrotic humans.

“…It is composed of component molecules, which vary between 18 and 70A in radius. A consistent finding in nephrotic subjects with a variety of underlying glomerular diseases has been a selective elevation above normal values of 0 for large, nearly impermeant dextrans of > 50A in radius (7)(8)(9)(10)(11)(12)(13)(14). With the use of pore theory this finding has been interpreted to indicate that the GCW is perforated by two parallel populations of pores, which vary widely in radius.…”

“…The 0 for each discrete fraction was derived by dividing its urine-to-plasma concentration ratio by that of inulin. An autoanalyzer technique which has been described elsewhere was used to assay inulin, PAH, and dextran concentrations (7)(8)(9)(10)). An enzymelinked immunosorbent assay was used to determine the simultaneous clearances of endogenous IgG and albumin (7)(8)(9)(10).…”

“…An autoanalyzer technique which has been described elsewhere was used to assay inulin, PAH, and dextran concentrations (7)(8)(9)(10)). An enzymelinked immunosorbent assay was used to determine the simultaneous clearances of endogenous IgG and albumin (7)(8)(9)(10). The dextran sulfate used in both clearance and various in vitro studies was tritiated, and its specific activity in all biological and artificial fluids was determined by scintillation counting.…”

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

“…Many renal diseases are characterized by heterogeneity in single-nephron GFR, tubular function, and distal salt delivery (3,31,79). Moreover, in the diseased kidney, the focal distribution of vascular/glomerular lesions suggests a heterogeneity regarding the pressure signals to these sites (31,117). It is not difficult to envision a need for individual nephron control under such conditions.…”

Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft.

“…I-,um thick sections of the paraffin-embedded biopsy material were cut and stained with periodic acid Schiff reagent. A dedicated computer system (Southern Micro Instruments, Atlanta, GA) consisting of a video camera, monitor, light microscope, and digitizing tablet was used to perform measurements (15,16). The average number of glomeruli examined per biopsy was 25 in group 1 and 32 in group 2.…”