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Phosphorus-Induced Nephrocalcinosis and Kidney Function in Female Rats¹

J. Ritskes-Hoitinga^*, A. G. Lemmens^*, L. H. J. C. Danse and A. C. Beynen^*,¶

^* Department of Laboratory Animal Science, State University, 3508 TD Utrecht National Institute of Public Health and Environmental Protection, 3720 BA Bilthoven and ^¶ Department of Human Nutrition, Agricultural University, 6700 EV Wageningen, the Netherlands

The question was addressed whether dietary phosphorus—induced nephrocalcinosis in rats is associated with impaired kidney function. Weanling female rats were fed purified diets containing either 0.4 or 0.6% (wt/wt) phosphorus for 28 d. The diet containing 0.6% phosphorus produced marked kidney calcification, as determined both by chemical analysis of kidney calcium and histological examination in kidney sections. Histological examination did not show calcification in stomach, lung, heart or thoracic aorta, which are predisposition sites of metastatic calcification in secondary renal hyperparathy-roidism. In rats fed the 0.6% phosphorus diet, phosphorus retention and urinary excretion were greater compared with rats fed the 0.4% phosphorus diet. The following indicators of kidney function were examined: water intake, urinary volume, urine and plasma osmolality, urine and plasma creatinine, urine and plasma urea, urea and creatinine clearance and urinary albumin excretion. Of these indicators, only urinary albumin excretion was significantly increased in rats fed the nephrocalcinogenic diet. In a further experiment, the increase of urinary albumin was reproduced. After pooling the results of the two experiments, in individual rats fed the 0.6% phosphorus diet, the concentration of kidney calcium was found to be positively related with kidney weight expressed relative to body weight (r = 0.82, n = 22) and with albumin excretion in urine (r = 0.79, n = 28). The increased weight of calcinotic kidneys was mainly due to both calcium deposition and tubular hyperplasia. It is concluded that dietary phosphorus—induced nephrocalcinosis is associated with impaired kidney function in rats.

KEY WORDS: • rat • nephrocalcinosis • calcium • phosphorus • kidney function

¹ J. Ritskes-Hoitinga is supported by Unilever Research Laboratory, Vlaardingen, the Netherlands.

Manuscript received 20 January 1989. Revision accepted 19 April 1989.

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