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

. Objectives.  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. Design and setting.  Population-based study of 209 community-dwelling subjects, mean age 76 years. Interventions.  Four months’ treatment study with oral vitamin B12, folic acid and B6 or placebo. Main outcome measures.  Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B12 and folate, age and sex. Results.  Elevated cystatin C (>1.55 mg L−1) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (≥16 μmol L−1) occurred in 53% and elevated MMA (≥0.34 μmol 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 B12- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B12 (4%), and for MMA, cystatin C (8%) and vitamin B12 (2%). Conclusions.  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.