High phosphorus diet rapidly induces nephrocalcinosis and proximal tubular injury in rats

The development of nephrocalcinosis and the time course of changes in kidney function, especially proximal tubular function, were studied in young male rats fed a high-phosphorus diet. The animals were fed a purified diet with a phosphorus content of either 0.5% (normal phosphorus diet) or 1.5% (high-phosphorus diet). In the group fed the high-phosphorus diet, nephrocalcinosis was found in 4 of 42 rats after 1 d of feeding and in all rats of this group at 3 d. The degree of nephrocalcinosis gradually increased with time. Upon histological observation by electron microscopy, vacuoles, lysosomes and swelling of microvilli in the proximal tubules were observed in rats fed the high-phosphorus diet after 1 d of feeding. Giant lysosomes with deposition of calcium and deposition of hydroxyapatite in mitochondria were observed in the proximal tubules of rats fed the high-phosphorus diet at 3 d. Albumin concentration in the urine of these rats was significantly increased at 3 d. The activity of N-acetyl-beta-D-glucosaminidase in the urine was also significantly increased after 1 d of feeding the high-phosphorus diet, and then reached a plateau. The beta 2-microglobulin concentration in the urine of rats fed the high-phosphorus diet was significantly increased at 14 d, and increased more toward 21 d. We concluded that nephrocalcinosis and injury to the proximal tubules are rapidly induced in rats fed a high-phosphorus diet.