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Acute Changes in Inorganic Phosphorus, Urea, and Alkaline Phosphatase of Plasma and Glomerular Filtration Rate during the Development of Soft Tissue Calcification in the KK Mice Fed a Diet Low in Magnesium and High in Phosphorus

Biological Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan

It has previously been reported that KK mice, when fed a semisynthetic diet low in magnesium and high in phosphorus, developed severe calcifications in soft tissues. This report describes various changes and some relationships among them which were induced by feeding this diet for only a few days. The changes include renal calcification, a decrease in glomerular filtration rate, a decrease in disappearance rate of plasma urea, hyperuremia, hyperphosphatemia, calcification of heart and other soft tissue, and a decrease of alkaline phosphatase activity subsequent to transient elevation. These changes were closely related to each other and developed in the described order. Since the changes were completely prevented by the supplement of magnesium alone, the relative deficiency of dietary magnesium is a major causal factor. However, none of these changes developed in the control ICR mice. The systemic study of the KK mice fed this diet revealed that the reduction of glomerular filtration rate caused by the deposition of calcium salts within the renal tubules resulted in the development of hyperuremia and hyperphosphatemia. The hyperphosphatemia brought about a rise in product of Ca x Pi, which was the main cause of the calcification of heart and other soft tissues.