Faculty Bibliography

We have previously demonstrated that long-term dietary protein restriction ameliorates proteinuria and limits glomerular structural injury in rats with nephrotoxic serum nephritis. In the present study, we examined the influence of short-term dietary protein restriction on glomerular permselectivity. As compared to nephritic rats maintained on a normal protein diet, whole kidney and single nephron hemodynamics were lower in nephritic rats subjected to dietary protein restriction of three days duration (glomerular filtration rate: 0.79 +/- 0.10 vs. 1.46 +/- 0.11 ml/min, P less than 0.003; renal plasma flow rate: 2.50 +/- 0.34 vs. 3.96 +/- 0.38 ml/min, P less than 0.02; glomerular capillary pressure: 44 +/- 1 vs. 53 +/- 1 mm Hg, P less than 0.002; proteinuria: 77 +/- 15 vs. 224 +/- 14 mg/24 hr, P less than 0.01). This was associated with a rise in afferent resistance, from 2.99 +/- 0.77 to 5.45 +/- 0.94 dyn.sec.cm-5, NS. In nephritic rats maintained on 24% protein, fractional clearances were elevated above control values for neutral dextrans with molecular radii exceeding 50 A but were depressed for those with molecular radii below 30 A (P less than 0.05). Dietary protein restriction elevated the fractional clearances of dextrans with radii less than 30 A while depressing the fractional clearances of dextrans with radii greater than 50 A (P less than 0.05). The proportion of glomerular filtrate permeating the shunt pathway was elevated above control values in nephritic rats on the 24% protein diet but declined in those fed the low protein diet (NSN-24%: 0.86%; NSN-6%: 0.31%; control: 0.19%).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the clinical features, pathologic findings, and course of 18 patients who were found to have glomerular disease at the time of hospitalization with manifestations of acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex at New York University Medical Center, New York, NY, during 1984 through 1987. Focal glomerulosclerosis, characterized by segmental and/or global collapse of capillary walls, was observed in 15 of these patients; mesangial proliferation in 2, and membranous nephropathy in 1. Those with focal glomerulosclerosis typically demonstrated heavy proteinuria without edema or hypertension and progressed rapidly to renal failure in less than 1 year from the time of discovery. This form of focal glomerulosclerosis is characterized by a fulminant course, the collapse type of sclerosis, and the frequent occurrence of uremia without advanced glomerular obliteration. The absence of widespread glomerular sclerosis and the rapid course suggest that unique renal hemodynamic mechanisms may be responsible for the progression

We have previously reported amelioration of heavy proteinuria, vascular sclerosis and glomerular structural damage by antihypertensive therapy in nephrotoxic serum nephritis (NSN). In the present study, we examine glomerular permselectivity in this hypertensive form of NSN and the effect of hypertension treatment on size-selective barrier function. Mean arterial pressure was maintained at normotensive levels (mean 123 +/- 3 mm Hg) with a combination of hydralazine, hydrochlorthiazide and reserpine in 7 nephritic rats, while 10 untreated rats remained hypertensive (mean 165 +/- 4 mm Hg). At six weeks, glomerular filtration rate was reduced in untreated rats (mean 0.54 ml/min) but was preserved in those rendered normotensive (mean 1.71 ml/min), P less than 0.02). Twenty-four-hour urinary protein excretion, mean 371 +/- 74 mg in hypertensive nephritic rats, was markedly reduced in rats on the antihypertensive regimen to a mean of 120 +/- 17 mg (P less than 0.02), as was 24-hour urinary gamma-globulin excretion (mean 35 +/- 9 mg in untreated vs. 16 +/- 2 mg in treated). Fractional clearances of tritiated polydisperse neutral dextrans were significantly enhanced for molecular radii exceeding 50 angstroms in hypertensive animals, indicative of a loss of glomerular size permselectivity. Rats on antihypertensive therapy did not develop such a size selective defect. Thus, hypertensive rats with nephrotoxic serum nephritis develop 'gaps' in the glomerular basement membrane which allow the excretion of large molecular weight neutral dextrans and gamma-globulin. This defect in glomerular permselectivity can be averted with antihypertensive therapy

We examined the effect of acute reduction in renal perfusion pressure on proteinuria and glomerular permselectivity in a model of nephrotoxic serum nephritis which is characterized by hypertension, heavy proteinuria and severe structural injury. Sequential dextran sieving studies were performed after two weeks of nephritis in 10 uninephrectomized rats at their basal elevated blood pressure levels (154 +/- 3 mm Hg) and at lowered renal perfusion pressure of 105 to 110 mm Hg, achieved by adjusting a ligature around the aorta above the origin of the renal artery. Glomerular filtration rate (GFR) decreased from 1.35 +/- 0.24 to 0.95 +/- 0.19 ml/min (P less than 0.002), while urinary protein excretion (factored for filtration rate) declined from 0.69 +/- 0.2 to 0.39 +/- 0.1 mg per ml GFR (P less than 0.002) at the lower perfusion pressure. A companion protocol documented a modest reduction in renal plasma flow (RPF) from 4.96 +/- 0.48 to 4.44 +/- 0.63 ml/min (P less than 0.05) and a decline in glomerular transcapillary hydraulic pressure difference (delta P) from 43 to 33 mm Hg (P less than 0.001) during the ligature maneuver. In the hypertensive state, fractional clearances of neutral dextrans (theta ND) with molecular radii exceeding 40 A were elevated in nephritic rats as compared to uninephrectomized non-nephritic controls. With reduction in renal perfusion pressure. Theta ND uniformly declined toward control values and remained significantly elevated only for molecular radii exceeding 55 A. The calculated fraction of glomerular filtrate passing through a non-size discriminatory shunt, pathway was 0.93% during the hypertensive period and was reduced at lower perfusion pressures to 0.52% (to be compared to 0.19% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)