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 pu rified diet with a phosphorus content of either 0.5% (normal phosphoru s diet) or 1.5% (high-phosphorus diet). In the group fed the high-phos phorus diet, nephrocalcinosis was found in 4 of 42 rats after 1 d of f eeding and in all rats of this group at 3 d. The degree of nephrocalci nosis 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 di et after Id of feeding. Giant lysosomes with deposition of calcium and deposition of hydroxyapatite in mitochondria were observed in the pro ximal tubules of rats fed the high-phosphorus diet at 3d. Albumin conc entration in the urine of these rats was significantly increased at 3d . The activity of N-acetyl-beta-D-glucosaminidase in the urine was als o significantly increased after 1 d of feeding the high-phosphorus die t, and then reached a plateau. The beta(2)-microglobulin concentration in the urine of rats fed the high-phosphorus diet was significantly i ncreased at 14 d, and increased more toward 21 d. We concluded that ne phrocalcinosis and injury to the proximal tubules are rapidly induced in rats fed a high-phosphorus diet.