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

与eGFR大于60 ml/min/1.73 m2的伊加肾病相比，糖尿病肾病的肾脏α-Klotho表达显著降低，尿钙排泄显著升高。多元回归分析显示α-Klotho mRNA与钙排泄呈负相关。我们还证实，与非糖尿病小鼠相比，STZ诱导的糖尿病肾病小鼠的肾脏α-Klotho mRNA减少近50%，钙排泄增加。与野生型小鼠相比，杂合α-Klotho基因敲除小鼠的高钙尿症加重，每只小鼠均患有STZ诱导的糖尿病肾病。因此，在人类和小鼠糖尿病肾病中，α-Klotho在远曲小管中的表达降低。肾脏α-Klotho丢失可能影响早期糖尿病肾病的尿钙排泄。然而，我们不能证实肾α-Klotho缺乏与糖尿病肾病骨代谢异常的直接相关性。

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.