Severely reduced production of Klotho in human chronic renal failure kidney

We recently identified a novel gene, termed klotho (hl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the hi gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short lifespan and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in hi mutant mice. Furthermore, the hi gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of hi mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in hi gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients. (C) 2001 Academic Press.