Laboratory Investigation

Kidney International (1980) 17, 722–731; doi:10.1038/ki.1980.85

Renal toxicity of phosphate in rats

Lewis L Haut1, Allen C Alfrey1, Stephen Guggenheim1, Bruce Buddington1 and Nancy Schrier1

1Departments of Medicine and Pathology, Veterans Administration Hospital and the University of Colorado School of Medicine, Denver, Colorado

Correspondence: Dr Allen C Alfrey, Chief, Renal Medicine, Veterans Administration Medical Center, 1055 Clermont Street, Denver, Colorado 80220, USA

Received 11 September 1978; Revised 29 October 1979.

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Abstract

Renal toxicity of phosphate in rats. To evaluate the mechanism by which phosphate induces renal injury, we placed uninephrectomized, partially nephrectomized, and intact rats on dietary phosphorus intakes varying between 0.5 and 2% for 18 weeks. None of the animals on a normal phosphorus intake (0.5%) had any abnormalities. Four out of six intact animals on a 1% phosphorus diet had kidney calcium concentrations within the normal range, and only one showed any histologic changes. In contrast, all but one partial and uninephrectomized animals on a 1% phosphorus diet had increased kidney calcium content concentration, and five of the six studied had histologic changes. The degree of calcification and histologic changes in the uninephrectomized animals on a 1% phosphorus diet was similar to that found in the intact animals on a 2% phosphorus diet. Animals on a 3% phosphorus diet plus disodium ethane-1-hydroxy-1-1-diphosphonate (EHDP) had significantly less calcification and histologic changes than did animals on a similar diet without EHDP. Conclusion. As renal functional mass is reduced, the nephrotoxicity of phosphorus is greatly enhanced Phosphorus-induced renal injury is mediated through calcium phosphate deposition in the kidney. This results from intrarenal causes, because the kidney calcification can be related to phosphate excreted per functional unit rather than plasma phosphate concentrations.

La toxicité rénale du phosphate chez le rat. Pour évaluer le mécanisme par lequel le phosphate détermine des lésions rénales, des rats uninéphrectomisés, partiellement néphrectomisés, et intacts ont reçu des apports de phosphate alimentaire divers compris entre 0,5 et 2% pendant 18 semaines. Aucun des animaux soumis à un apport de phosphorus normal (0,5%) n'a eu d'anomalie. Quatre parmi les six animaux intacts soumis à un apport de 1% avaient des concentrations rénales de calcium comprises dans l'éventail des valeurs normales et seulement un d'entre eux avait des lésions histologiques. Au contraire, les animaux partiellement néphrectomisés ou uninéphrectomisés soumis à un apport de 1% de phosphorus avaient tous, sauf un, une augmentation du contenu rénal en calcium. Cinq parmi les six étudiés du point de vue histologique avaient des lésions. L'importance de la calcification et des modifications histologiques chez les animaux uninéphrectomisés soumis à un apport de 1% de phosphorus était comparable à celle observée chez les animaux intacts soumis à un apport de 2% de phosphorus. Les animaux soumis à un apport de 3% de phosphorus et à le disodium ethane-1-hydroxy-1-1-diphosphonate (EHDP) avaient significativement moins de calcification et de modifications histologiques que les animaux recevant la même alimentation sans EHDP. Conclusion. La réduction de la masse fonctionnelle rénale augmente considérablement la toxicité du phosphore. L'atteinte rénale liée au phosphore a pour médiateur la déposition de calcium phosphate dans le rein. Cela est la conséquence d'un mécanisme intra-rénal puisque la calcification est en rapport avec l'excrétion de phosphore par unité fonctionnelle plutôt qu'avec la concentration plasmatique de phosphore.

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