Hyperfiltration and Conservation of Renal Function in Hypertensive Nephrosclerosis Patients

Abstract

Renal glomerular hyperfiltration has been proposed as an important contributing factor to the progression of hypertensive nephrosclerosis in rats with reduced renal mass. However, no clinical studies have assessed the role of glomerular hyperfiltration in the pathogenesis of hypertensive nephrosclerosis in humans. In a prospective, randomized, long-term blood pressure control study with up to 3 years follow-up, we showed that good blood pressure control with a mean diastolic blood pressure < or = 95 mm Hg preceded by a 2- to 4-month period of diastolic blood pressure < or = 80 mm Hg improved renal function in hypertensive nephrosclerosis patients. Patients treated with minoxidil, an angiotensin-converting enzyme inhibitor (enalapril), or a calcium entry blocker (nifedipine) had improvement in renal function, as indicated by a positive slope of the reciprocal serum-creatine concentration versus time and an increment in glomerular filtration rate. These results suggested that improvement in renal function occurred with these major types of antihypertensive drug treatment. To assess the renal hemodynamics of minoxidil, enalapril, and nifedipine, eight patients with hypertensive nephrosclerosis were admitted to the General Clinical Research Center for renal clearance studies on each drug while ingesting a fixed-calorie, 12% protein, 40% fat, and 100 mEq Na/d diet. Mean blood pressure, effective renal plasma flow, and renal vascular resistance did not change during the three phases of treatment. However, minoxidil treatment increased the glomerular filtration rate by 48% versus enalapril and by 79% versus nifedipine. Since minoxidil treatment improves renal function while causing a relative hyperfiltration, glomerular hyperfiltration per se is an unlikely mechanism for the progression of hypertensive nephrosclerosis in humans.