Renal functional reserve in experimental chronic glomerulonephritis

Loss of renal functional reserve, that is, absence of the glomerular vasodilatory response to amino-acid infusion, has been interpreted as equivalent to glomerular hyperperfusion/hypertension, and therefore proposed as a marker of high risk for progressive glomerular sclerosis. To substantiate the validity of this hypothesis we evaluated the renal response to glycine and the extent of glomerular damage 10-12 weeks after induction of anti-glomerular basement membrane glomerulonephritis with or without superimposed clip hypertension. Untreated rats and rats chronically treated with quinapril, a converting-enzyme inhibitor, were studied. In untreated groups, loss of renal functional reserve was demonstrated since GFR, single-nephron GFR (SNGFR) and plasma flow (SNPF) did not increase during glycine infusion. The absence of renal reserve was associated with glomerular hyperfusion/hypertension, and development of proteinuria and glomerulosclerosis. Quinapril reduced proteinuria and diffuse sclerosis in anti-glomerular basement membrane GN, and decreased blood pressure and segmental glomerulosclerosis in antiglomerular basement membrane GN with superimposed clip hypertension. Both treated groups demonstrated a restoration of renal functional reserve, as depicted by increases in GFR, SNGFR, and SNPF after glycine, despite persistence of glomerular hyperperfusion/hypertension. These data demonstrate that renal functional reserve testing, although it does not detect glomerular hyperperfusion/hypertension, can provide information on the progression of glomerular damage.