Hyperhomocysteinemia in relation to plasma free amino acids, biomarkers of inflammation and mortality in patients with chronic kidney disease starting dialysis therapy.
BACKGROUND
Plasma levels of total homocysteine (tHcy) and free amino acids (AAs) are influenced by nutritional status in patients with chronic kidney disease (CKD), whereas the role of chronic inflammation is not clear.


METHODS
In a cross-sectional analysis, fasting levels of plasma tHcy, total cysteine (tCys), AA, serum albumin (Alb), and several inflammation markers, including C-reactive protein (CRP), were analyzed in a cohort of 250 patients with CKD starting renal replacement therapy. Patients were followed up during a 4-year period to assess overall mortality in relation to basal tHcy level.


RESULTS
Ninety-three patients (37%) with signs of inflammation (CRP > or = 1 mg/dL) had significantly lower levels of tHcy, tCys, and serum Alb than 157 noninflamed patients. tHcy and tCys levels correlated positively with serum Alb levels and negatively with CRP levels (rho = -0.24; P < 0.0001; rho = -0.15; P < 0.05, respectively) and other inflammation markers. tHcy and tCys correlated significantly with levels of several AAs. The presence of both inflammation and malnutrition was associated with lower tHcy levels than when malnutrition was present without inflammation. Multivariate analysis showed that serum Alb, CRP, plasma folate, and vitamin B12 levels were independently associated with tHcy levels after adjustment for other variables. tHcy, but not tCys, level was significantly greater in survivors than nonsurvivors, and Kaplan-Meier analysis showed that greater tHcy level was associated with better survival.


CONCLUSIONS
Plasma tHcy and tCys levels are interrelated to plasma AA levels and were lower in patients with inflammation. Thus, inflammation may contribute to the reverse association between tHcy level and mortality in patients with CKD starting renal replacement therapy.
Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Mohamed E
ME
Suliman
Peter
P
Stenvinkel
A Rashid
AR
Qureshi
Peter
P
Bárány
Olof
O
Heimburger
Björn
B
Anderstam
Anders
A
Alvestrand
Bengt
B
Lindholm
D000596:Amino Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003545:Cysteine / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000503:physiopathology; D007249:Inflammation; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D044342:Malnutrition / Q000503:physiopathology; D008875:Middle Aged; D009752:Nutritional Status; D006435:Renal Dialysis; D016019:Survival Analysis
D000596:Amino Acids; D015415:Biomarkers; D006710:Homocysteine; D003545:Cysteine