Cystatin C is an independent predictor of fasting and post-methionine load total homocysteine concentrations among stable renal transplant recipients

Background: An increased prevalence of hyperhomocysteinemia with an increased incidence of cardiovascular disease events has been reported among stable renal transplant recipients (RTRs). Preliminary studies in a small number of these individuals have shown that serum creatinine and cystatin C, both markers of kidney function and glomerular filtration rate, are independent determinants of fasting tHcy concentrations; however, determinants of tHcy concentrations after a methionine load have not been studied. Methods: We determined the prevalence of both fasting and 4-h post-methionine load (PML) tHcy concentrations in 78 stable RTRs and compared the role of cystatin C with the role of serum creatinine as determinants of fasting and PML tHcy. Results: Of the 78 RTRs, 21 (26.9%) had fasting and PML tHcy within the respective reference intervals, and 57 (73.1%) had increased plasma tHcy. Of these 57 RTRs, 22 had fasting hyperhomocysteinemia, 9 had PML hyperhomocysteinemia, and 26 had combined hyperhomocysteinemia (both fasting and PML). Unadjusted Pearson correlations showed that fasting plasma tHcy correlated with both cystatin C (r = 0.564; P <0.001) and creatinine (r = 0.519; P <0.001) and that increases in PML tHcy modestly correlated with cystatin (r = 0.205; P = 0.072), but not creatinine (r = 0.057; P = 0.624). General linear regression modeling with stepwise analysis of covariance showed that both cystatin C (partial R = 0.554; P <0.001) and creatinine (partial R = 0.535; P <0.001) were independent predictors of fasting tHcy, but of the two, only cystatin C (partial R = 0.242; P = 0.035) was an independent predictor of increased PML tHcy. Conclusions: Clinically stable RTRs have an excess prevalence of moderate hyperhomocysteinemia, and additional cases can be detected by methionine loading. Both creatinine and cystatin C are independent predictors of fasting tHcy in these individuals; however, only cystatin C is a determinant of tHcy concentration after a methionine load, probably because cystatin C is a more sensitive marker of glomerular filtration rate than serum creatinine.