The Increase of Plasma Homocysteine Concentrations with Age Is Partly due to the Deterioration of Renal Function as Determined by Plasma Cystatin C

Abstract

One of the main determinants of plasma homocysteine in healthy subjects is serum creatinine. In the present study, we therefore investigated the relation between plasma homocysteine concentration, serum creatinine and a new marker for glomerular filtration rate, plasma cystatin C concentration. Cystatin C reflects the glomerular filtration better than serum creatinine and is not related to the muscle mass and formation of creatinine. The study group consisted of 255 healthy subjects from a well-defined area in the southern part of Sweden. The concentration of plasma homocysteine was increased in men compared to women. This difference disappeared when men and women were stratified by serum creatinine values. Statistically significant correlations were noted between plasma homocysteine and age, plasma cystatin C and serum creatinine. It is shown that plasma homocysteine is not only correlated to serum creatinine as a result of renal function but also as a result of the relationship between homocysteine production and creatine-creatinine synthesis. Using linear regression we were able to show that plasma cystatin C had a higher explanatory value than age. Serum creatinine showed a lower explanatory power than age. The findings in the present study might suggest that the increase of plasma homocysteine concentration with age could be partly due to the deterioration of renal function.

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

“…After vitamin treatment, single subjects with higher serum creatinine concentrations had metabolite concentrations above the reference limits of the laboratory. Somewhat unexpectedly (Norlund et al, 1998;Bostom et al, 1999;Brattström & Wilcken, 2000;Hvas et al, 2000), metabolite concentrations did not correlate to serum creatinine. This might call for a better marker for renal function in this elderly population.…”

“…This might explain the considerable overlap in signs and symptoms of deficiency. Elevated concentrations of plasma total homocysteine (P-tHcys) is seen in B vitamin deficiency (B 12 , folic acid, B 6 ), impaired renal function (Norlund et al, 1998;Bostom et al, 1999;Brattström & Wilcken, 2000) and hypothyroidism (Hussein et al, 1999). Certain lifestyle factors may also contribute (Nygård et al, 1998;Stolzenberg-Solomon et al, 1999;de Bree et al, 2001).…”

Cystatin C as a Determinant of Fasting Plasma Total Homocysteine Levels in Coronary Artery Disease Patients With Normal Serum Creatinine

“…16,17 An earlier analysis 22 with cystatin C as a surrogate for glomerular filtration rate in healthy subjects had suggested that the well-characterized increase in plasma tHcy levels with advancing age might be due, in part, to an age-related decline in renal function. Moreover, we recently showed that cystatin C, but not serum creatinine, was an independent predictor of fasting tHcy levels in renal transplant recipients with normal renal function (ie, serum creatinine levels Յ1.5 mg/dL).…”

Effect of fortified spread on homocysteine concentration in apparently healthy volunteers

“…Differences in homocysteine metabolism between the genders may explain this as males have a lower remethylation rate as compared to females (Fukagawa et al, 2000). Another explanation could be the differences in lean body mass (Norlund et al, 1998) or the hormonal status (Andersson et al, 1992;Giltay et al, 1998).…”