The Influence of Orthophosphate on the Renal Handling of Inorganic Pyrophosphate in Man and Dog

Abstract

1. The urinary excretion of inorganic pyrophosphate (PP1), a known inhibitor of the growth and aggregation of crystals of calcium phosphate and calcium oxalate, increases after ingestion of orthophosphate (P1). This effect may contribute to the apparent ability of oral phosphate to reduce the formation of urinary stones in man. This paper is a study of the mechanism by which P1 increases PP1 excretion, investigated by renal clearance techniques in man and renal arterial infusion in dogs. PP1 in plasma was measured by an isotope-dilution method after ion-exchange chromatography. 2. The mean renal clearance of endogenous PP1 in ten men was 7·9 ± 1·7 (se) ml/min, and the mean ratio of PP1 clearance to creatinine clearance was 008 ±002 (se). The oral ingestion of P1 increased the urinary excretion and renal clearance of PP1 about threefold, without significantly changing its concentration in plasma. 3. In dogs, the infusion of P1 into one renal artery caused a greater increase in urinary PP1 from the infused than from the non-infused kidney, an effect that could be accentuated by simultaneous intravenous infusion of PP1. In dogs, only 1–3% of an injected or infused dose of PP1 appeared intact in the urine, regardless of whether it was infused into the systemic or renal circulation. 4. These results suggest that P1 has a direct effect on the kidney to increase the excretion of PP1. It is possible that P1 either interferes with tubular reabsorption of PP1, perhaps by competing for a common tubular transport mechanism, or that P1 diminishes the intrarenal hydrolysis of PP1.