Renal Excretion of Inulin, Creatinine and Ferrocyanide, at Normal and Reduced Clearance Levels in the Dog

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Abstract
In 54 control periods in 15 normal (anesthetized) dogs, the ratios of the clearances of creatinine and ferrocyanide to inulin (Ccr/Cin and Cfer/Cin) differed significantly from unity, averaging 0.936 ± 0.047 and 0.932 ± 0.059, respectively. However, in these animals, clearance ratios did not vary with Cin, or urine flow, provided that Cin exceeded 2.3 ml/min/kg (lower limit of ‘normal’). In these 15 dogs, Cin varied directly with perfusion pressure, when the latter was transiently reduced by either hexamethonium, hemorrhage or aortic occlusion. Values for Cin below 2.3 ml/min/kg were associated with decreased ratios for Ccr/Cin and Cfer/Cin. This phenomenon was uninfluenced by phloridzin or probenecid, was potentiated by urinary concentration, and (at low clearance levels) was obliterated by elevating urine flow relative to Cin. Clearance deficits quickly and permanently disappeared when Cin was elevated above 2.3 ml/min/kg by restoration of perfusion pressure. Aberrant clearance ratios cannot easily be attributed to tubular damage because they were so promptly and permanently reversed, no histological evidence of immediate or delayed tubular necrosis followed their demonstration, and in six dogs with frank tubular necrosis following HgCl2, or clamping the renal artery, no clearance deficits accompanied comparable reductions in clearance level. The observed direct relationship between clearance ratios and Cin or urine flow, must therefore reflect partial permeability of the normal renal tubule allowing passive back diffusion of at least creatinine and ferrocyanide. In the normal dog, clearance values should probably be interpreted with caution at levels for Cin below 2.0 ml/min/kg.