Kidney international, 2012-03, Vol.81 (6), p.539-547
2012
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- Autor(en) / Beteiligte
- Titel
- Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion
- Ist Teil von
- Kidney international, 2012-03, Vol.81 (6), p.539-547
- Ort / Verlag
- Basingstoke: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of α-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 α-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 α-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 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0085-2538eISSN: 1523-1755DOI: 10.1038/ki.2011.423Titel-ID: cdi_proquest_miscellaneous_925717504
- Format
- –
- Schlagworte
- Adult, Animal models, Animals, Associated diseases and complications, Biological and medical sciences, Calcium (urinary), Calcium - urine, Calcium Channels - genetics, Calcium Channels - metabolism, Diabetes mellitus, Diabetes Mellitus, Experimental - chemically induced, Diabetes Mellitus, Experimental - complications, Diabetes Mellitus, Experimental - metabolism, Diabetes Mellitus, Experimental - urine, Diabetes. Impaired glucose tolerance, Diabetic Nephropathies - etiology, Diabetic Nephropathies - genetics, Diabetic Nephropathies - metabolism, Diabetic Nephropathies - urine, diabetic nephropathy, Down-Regulation, Endocrine pancreas. Apud cells (diseases), Endocrinopathies, Excretion, Glucuronidase - genetics, Glucuronidase - metabolism, HEK293 Cells, Heterozygote, Humans, Hypercalciuria, Hypercalciuria - etiology, Hypercalciuria - genetics, Hypercalciuria - metabolism, Hypercalciuria - urine, hypoxia, IgA nephropathy, Kidney, Kidney diseases, Kidney Tubules, Distal - metabolism, Kidneys, Male, Medical sciences, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, mRNA, Multiple regression analysis, Nephrology. Urinary tract diseases, Reabsorption, Receptors, Cell Surface - deficiency, Receptors, Cell Surface - genetics, Receptors, Cell Surface - metabolism, RNA, Messenger - metabolism, Streptozocin, Time Factors, Transfection, TRPV Cation Channels - genetics, TRPV Cation Channels - metabolism, Tubules, Urinary system involvement in other diseases. Miscellaneous, Young Adult