Nephrotoxic serum nephritis with hypertension: Perfusion pressure and permselectivity

Abstract

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)