Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly

To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. Population-based study of 209 community-dwelling subjects, mean age 76 years. Four months' treatment study with oral vitamin B-12, folic acid and B-6 or placebo. Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B-12 and folate, age and sex. Elevated cystatin C (> 1.55 mg L-1) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (>= 16 mu mol L-1) occurred in 53% and elevated MMA (>= 0.34 mu mol L-1) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B-12- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B-12 (4%), and for MMA, cystatin C (8%) and vitamin B-12 (2%). The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.