NDT Advance Access originally published online on September 17, 2006
Nephrology Dialysis Transplantation 2007 22(1):209-217; doi:10.1093/ndt/gfl510
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation
1Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden, 2Harbor-UCLA Medical Center, Torrance, California 90502, USA and 3Baxter Healthcare Corporation, Round Lake, IL 600073, USA
Correspondence and offprint requests to: Bengt Lindholm, Renal Medicine and Baxter Novum, K56, Karolinska University Hospital Huddinge, Karolinska Institutet, S-141 86 Stockholm, Sweden. Email: bengt.lindholm{at}ki.se
 |
Abstract |
|---|
Background. The reason(s) for the apparently paradoxical ‘reverse’ association in end-stage renal disease (ESRD) patients in whom a low, rather than a high, total plasma total homocysteine (tHcy) level is an indicator of poor outcome remains unclear. The aim of this study was to examine whether the inverse association maintains, mitigates or reverses after comprehensive multivariate adjustment for the presence of wasting and inflammation as well as other potential confounders.
Methods. We studied 317 ESRD patients starting dialysis therapy. Fasting blood samples were taken for the analyses of tHcy, serum albumin, C-reactive protein (CRP), serum creatinine and plasma folate. Nutritional status was assessed by subjective global assessment (SGA). Survival was followed for up to 66 months; 105 patients died.
Results. Using Kaplan–Meier analysis, a low tHcy concentration (
30 µmol/l) was associated with higher all-cause and cardiovascular (CV) mortality (P < 0.05). Using Cox proportional analysis adjusting for age, gender, glomerular filtration rate = GFR, cardiovascular disease = CVD, plasma folate, total cholesterol and diabetes mellitus, the all-cause and CV mortality still tended to be high for patients with low tHcy. Adding nutritional and inflammation markers (Body mass index = BMI, SGA, serum creatinine, serum albumin and CRP), a low tHcy level was no longer associated with higher mortality but a trend for high tHcy was observed.
Conclusions. The link between wasting inflammation and a low tHcy appears to be responsible for the reverse association between plasma tHcy and clinical outcome in ESRD patients. After adjustment for confounders including nutritional and inflammation markers, a trend towards increased death risk for high, rather than low, tHcy levels was apparent after adjustment.
Keywords: end-stage renal disease; homocysteine; inflammation; mortality; wasting
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Stamopoulos, P. Bouziotis, D. Benaki, C. Kotsovassilis, and P. N. Zirogiannis Utilization of nanobiotechnology in haemodialysis: mock-dialysis experiments on homocysteine Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3234 - 3239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stenvinkel, J. J. Carrero, J. Axelsson, B. Lindholm, O. Heimburger, and Z. Massy Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient: How Do New Pieces Fit into the Uremic Puzzle? Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 505 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Movilli Homocysteine and reverse epidemiology Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2093 - 2093. [Full Text] [PDF]
|
|
|
|
|
|
A. Kazory and A. A. Ejaz Removal of BNP and inflammatory cytokines by haemodiafiltration in refractory heart failure Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2093 - 2094. [Full Text] [PDF]
|
|
|
|
|
|
M. E. Suliman, P. Stenvinkel, A. R. Qureshi, K. Kalantar-Zadeh, and B. Lindholm Reply Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2093 - 2093. [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Johansen Exercise in the End-Stage Renal Disease Population J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1845 - 1854. [Abstract] [Full Text] [PDF]
|
|