A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Abstract

Abstract. An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.5 Ϯ 14.7 (mean Ϯ SD) years, who included 199 men and 55% individuals with diabetes. tHcy was 24.4 Ϯ 11.8 mol/L, and 94% of the patients had hyperhomocysteinemia (tHcy Ͼ13.5 mol/L). tHcy had weak to moderate but statistically significant bivariate and multivariate correlations with some laboratory markers of nutrition (serum albumin, prealbumin, creatinine, and urea nitrogen) but no significant correlation with serum C-reactive protein or two proinflammatory cytokines (IL-6 and TNF-␣).During 12 mo of follow-up, 191 MHD patients were hospitalized, 37 died, nine underwent renal transplantation, and 38 transferred out. Hospitalization rates were significantly higher in patients with lower tHcy levels. Mortality rate in the lowest tHcy quartile (17.4%) was significantly higher compared with other three quartiles (6.5 to 9.8%; Kaplan-Meier P ϭ 0.04). Relative risk of death for the lowest tHcy quartile, even after adjustment for case-mix and serum albumin, was 2.27 (95% confidence interval, 1.14 to 4.53; P ϭ 0.02). Hence, tHcy may be a more exclusive nutritional marker in MHD patients with no association with inflammatory measures. Despite a very high prevalence of hyperhomocysteinemia in MHD patients, lower values of tHcy are paradoxically associated with increased hospitalization and mortality. The lowest tHcy quartile confers a twofold increase in risk of death independent of hypoalbuminemia. The nutritional feature of tHcy in MHD patients may explain its reverse association with outcome.In the general population, an increased level of total plasma homocysteine (tHcy) is a risk factor for increased cardiovascular events and mortality (1-4). In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5-9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12). This seems to be due to the empirical association between a low tHcy and protein-energy malnutrition, which is per se a known risk factor for poor clinical outcome in dialysis patients (11,13,14). This recently described paradoxical association between tHcy and clinical outcome in dialysis patients has now been referred to as a possible component of the reversal of the cardiovascular risks (15-17). It is believed that both inflammation and protei...

Reverse Epidemiology of Lipid-Death Associations in a Cohort of End-Stage Renal Disease Patients

“…Additionally, a Cox multiple regression death hazard ratio revealed LDL particle size as a significant predictor of mortality. The results of our study support the findings of the few database studies [10,13,19] that have been published regarding this topic and discovered the existence of a reverse epidemiological effect regarding cholesterol variables and morality in ESRD patients.…”

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5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

“…In particular, HD patients often have rather skewed distributions of risk factors compared to the general population. Similar to the reverse epidemiology related to higher mortality in HD patients with low cholesterol, a few recent studies showed that lower levels of homocysteine were inversely correlated with mortality [7, 29]. In the study by Kalantar-Zadeh et al [7], they did not observe any correlation between homocysteine and body mass index or other inflammatory markers; however, they did observe a direct correlation between albumin and homocysteine.…”

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Baseline Oxysterols and Other Markers of Oxidative Stress, Inflammation and Malnutrition in the Vitamin E and Intima Media Thickness Progression in End-Stage Renal Disease (VIPER) Cohort

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