Glomerular ultrafiltration dynamics: historical perspective

Abstract

Our knowledge of the structure and function of the renal glomerulus is reviewed in a historical context. The glomerular corpuscles were first described by Malpighi in 1666. Subsequent injection studies led to conflicting claims concerning a glomerular-tubular connection. This connection was accepted only after the convincing demonstration of the anatomical relationship essentially as we now know it by Bowman in 1842. Ludwig was the first to propose that the mechanism of separation of fluid in the glomeruli was by ultrafiltration. Estimates of the ultrafiltration forces in mammals led to conflicting speculation as to whether or not filtration-pressure equilibrium was reached in glomerular capillaries. Results of direct determinations in some Munich-Wistar rats indicate filtration pressure equilibrium, an ultrafiltration coefficient (Kf) of 0.08 nl X s-1 X mmHg-1, and a strong influence of plasma flow on filtration rate (GFR). In contrast, evidence has been presented that filtration dynamics in other Munich-Wistar rats and several other strains of rats are characterized by filtration disequilibrium, a Kf of 0.04 nl X s-1 X mmHg-1, and a weak dependence of GFR on plasma flow. In conscious and anesthetized rats, kidney GFR is usually relatively stable in the presence of renal vasodilation. Filtration disequilibrium is reported in the dog and equilibrium in the squirrel monkey. Although predictions for humans suggest filtration disequilibrium, final conclusions await an in-depth analysis of direct measurements.