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 B(12), folic acid and B(6) or placebo.

Main Outcome Measures: 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.

Results: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol 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%).

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.