Renal toxicity of phosphate in rats.

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 toxicite renale du phosphate chez le rat. Pour evaluer le mecanisme par lequel le phosphate determine des lesions renales, des rats uninephrectomises, partiellement nephrectomises, et intacts ont recu des apports de phosphate alimentaire divers compris entre 0,5 et 2% pendant 18 semaines. Aucun des animaux soumis a un apport de phosphorus normal (0,5%) n'a eu d'anomalie. Quatre parmi les six animaux intacts soumis a un apport de 1% avaient des concentrations renales de calcium comprises dans l'eventail des valeurs normales et seulement un d'entre eux avait des lesions histologiques. Au contraire, les animaux partiellement nephrectomises ou uninephrectomises soumis a un apport de 1% de phosphorus avaient tous, sauf un, une augmentation du contenu renal en calcium. Cinq parmi les six etudies du point de vue histologique avaient des lesions. L'importance de la calcification et des modifications histologiques chez les animaux uninephrectomises soumis a un apport de 1% de phosphorus etait comparable a celle observee chez les animaux intacts soumis a un apport de 2% de phosphorus. Les animaux soumis a un apport de 3% de phosphorus et a le disodium ethane-1-hydroxy-1-1-diphosphonate (EHDP) avaient significativement moins de calcification et de modifications histologiques que les animaux recevant la meme alimentation sans EHDP. Conclusion. La reduction de la masse fonctionnelle renale augmente considerablement la toxicite du phosphore. L'atteinte renale liee au phosphore a pour mediateur la deposition de calcium phosphate dans le rein. Cela est la consequence d'un mecanisme intra-renal puisque la calcification est en rapport avec l'excretion de phosphore par unite fonctionnelle plutot qu'avec la concentration plasmatique de phosphore.