| First Author | Asai O | Year | 2012 |
| Journal | Kidney Int | Volume | 81 |
| Issue | 6 | Pages | 539-47 |
| PubMed ID | 22217880 | Mgi Jnum | J:196499 |
| Mgi Id | MGI:5488581 | Doi | 10.1038/ki.2011.423 |
| Citation | Asai O, et al. (2012) Decreased renal alpha-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. Kidney Int 81(6):539-47 |
| abstractText | Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of alpha-Klotho, a protein expressed predominantly in distal convoluted tubules that has a role in calcium reabsorption. We studied 31 patients with early diabetic nephropathy and compared them with 31 patients with IgA nephropathy and 7 with minimal change disease. Renal alpha-Klotho expression was significantly lower and urinary calcium excretion (UCa/UCr) significantly higher in diabetic nephropathy than in IgA nephropathy or minimal change disease. Multiple regression analyses indicated that alpha-Klotho mRNA was inversely correlated with calcium excretion. We next measured these parameters in a mouse model of streptozotocin (STZ)-induced diabetic nephropathy, characterized by glomerular hyperfiltration, as seen in early diabetic nephropathy. We also confirmed a reduction of renal alpha-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 alpha-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, alpha-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of alpha-Klotho may affect urinary calcium excretion in early diabetic nephropathy. |
