Despite the high prevalence of chronic kidney disease among the elderly, few studies have described their loss of kidney function. We sought to determine the progression of kidney dysfunction among a community-based cohort of elderly subjects. The cohort included 10 184 subjects 66 years of age or older, who had one or more outpatient serum creatinine measurements during each of two time periods: 1 July to 31 December 2001 and 1 July to 31 December 2003. A mixed effects model, including covariates for age, gender, diabetes mellitus, and comorbidity, was used to determine the rate of decline in estimated glomerular filtration rate (eGFR, in ml/min/1.73 m2) per year over a median follow-up of 2.0 years. Subjects with diabetes mellitus had the greatest decline in eGFR of 2.1 (95% CI 1.8-2.5) and 2.7 (95% CI 2.3-3.1) ml/min/1.73 m2 per year in women and men, respectively. The rate of decline for women and men without diabetes mellitus was 0.8 (95% CI 0.6-1.0) and 1.4 (95% CI 1.2-1.6) ml/min/1.73 m2 per year. Subjects with a study mean eGFR<30 ml/min/1.73 m2, both those with and without diabetes mellitus, experienced the greatest decline in eGFR. In conclusion, we found that the majority of elderly subjects have no or minimal progression of kidney disease over 2 years. Strategies aimed at slowing progression of kidney disease should consider underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older adults.

No abstract

No abstract

Methionine synthase reductase (MSR; gene name MTRR) is responsible for the reductive activation of methionine synthase. Cloning of the MTRR gene had revealed two major transcription start sites which, by alternative splicing, allows for two potential translation products of 698 and 725 amino acids. While the shorter protein was expected to target the cytosol where methionine synthase is located, the additional sequence in the longer protein was consistent with a role as a mitochondrial leader sequence. The possibility that MSR might target mitochondria was also suggested by the work of Leal et al. [N.A. Leal, H. Olteanu, R. Banerjee, T.A. Bobik, Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase, J. Biol. Chem. 279 (2004) 47536-47542.] who showed that it can act as the reducing enzyme in combination with MMAB (ATP:Cob(I)alamin adenosyltransferase) to generate adenosylcobalamin from cob(II)alamin in vitro. Here we examined directly whether MSR protein is found in mitochondria. We show that, while two transcripts are produced by alternative splicing, the N-terminal segment of the putative mitochondrial form of MSR fused to GFP does not contain a sufficiently strong mitochondrial leader sequence to direct the fusion protein to the mitochondria of human fibroblasts. Further, antibodies to MSR protein localized MSR to the cytosol, but not to the mitochondria of human fibroblasts or the human hepatoma line Huh-1, as determined by Western blot analysis and immunofluorescence of cells in situ. These data confirm that MSR protein is restricted to the cytosol but, based on the Leal study, suggest that a similar protein may interact with MMAB to reduce the mitochondrial cobalamin substrate in the generation of adenosylcobalamin.