title: Renal toxicity of phosphate in rats.
abstract: 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 phosporus is greatly enhanced. Phosphorus-induced renal injury is mediated through calcium phosphate deposition in the kidney. This results from intrarenal caused, because the kidney calcification can be related to phosphate excreted per functional unit rather than plasma phosphate concentrations.
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000139:chemically induced; D002130:Calcium Phosphates / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004164:Diphosphonates / Q000009:adverse effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010710:Phosphates / Q000009:adverse effects* / Q000378:metabolism; D051381:Rats
chemical_list: D002130:Calcium Phosphates; D004164:Diphosphonates; D010710:Phosphates