Impact of Homocysteinemia on Long-Term Renal Transplant Survival

Abstract

Aim. We prospectively followed a cohort of 202 renal transplant recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. Methods. Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. Results. Hyperhomocysteinemia (tHcy Ͼ15 mol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%) as opposed to women (37.1%). At the end of the follow-up period, 13 (6.4%) patients had died including 10 from cardiovascular disease, and 23 had (11.4%) had lost their grafts. Patient death with a functioning allograft was the most prevalent cause of graft loss (13 recipients). Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 mol/L; P ϭ .005). Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 mol/L; P ϭ .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR ϭ 5.50; 95% CI, 1.56 to 19.36; P ϭ .008) and age at transplantation (HR ϭ 1.07; 95% CI, 1.02 to 1.13; P ϭ .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss.Conclusions. This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.S HORT-AND LONG-TERM GRAFT and patient survivals after renal transplantation have improved considerably over the past three decades. However, life expectancy beyond 10 years is still considerably less than in the general population, mainly due to cardiovascular events. In fact, an accelerated form of atherosclerosis commonly occurs in these patients. Cardiovascular disease is the leading cause of morbidity and mortality in renal transplant recipients, accounting for approximately 40% of all deaths. 1,2 Classic cardiovascular risk factors (eg, dyslipidemia, hypertension, and diabetes) as well as nonmodifiable risk factors such as age, gender, and family history do not fully explain the cardiovascular disease. Among other predictors of atherosclerotic disease, attention has been drawn to the association between homocysteine and cardiovascular events. Clinical and epidemiological studies have shown that homocysteine measured in serum or plasma is a strong predictor of cardiovascular risk. 3,4 The results of early cross-sectional and case-control studies strongly support this hypothesis. 5,6 Prospective studies of patient populations known to be at high risk of cardiovascular events, including renal patients, consistently report strong associations between homocysteine and cardiovascular as well as all-cause mortality. [7][8][9][10][11][12][13][14][15][16] Elevated levels of fasting total ...