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.
Aras O
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455-0392, USA.
Tsai
M Y
MY
Hanson
N Q
NQ
Bailey
R
R
Rao
G
G
Hunninghake
D B
DB
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005215:Fasting; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis* / Q000209:etiology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008715:Methionine; D008875:Middle Aged; D012044:Regression Analysis
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D006710:Homocysteine; D008715:Methionine