The significance of Klotho in bone and mineral metabolism disorders in diabetes

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Renal α-Klotho expression was significantly lower and urinary calcium excretion significantly higher in diabetic nephropathy than in IgA nephropathy with an eGFR greater than 60 ml/min per 1.73m2 . Multiple regression analyses indicated that α-Klotho mRNA was inversely correlated with calcium excretion. We also confirmed a reduction of renal α-Klotho mRNA down to almost 50% and enhanced calcium excretion in mice with STZ-induced diabetic nephropathy in comparison with nondiabetic mice. Hypercalciuria was exacerbated in heterozygous α-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy. However, we cannot confirm the direct associations of renal α-Klotho deficiency with bone metabolism abnormalities in diabetic nephropathy.