IMMUNOLOGICAL FUNCTION AND SURVIVAL IN HEMODIALYSIS-PATIENTS

Background. Although the medical determinants of mortality in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) ar e well appreciated, the contribution of immunologic parameters to surv ival in such patients is unclear, especially when variations in age, m edical comorbidity and nutrition are controlled. In addition, although dysregulation of cytokine metabolisn has been appreciated in patients with ESRD, the association of these parameters with outcomes has not been established. Recently, the type of dialyzer used in patients' tre atment has been associated with survival, but the mechanisms underlyin g these findings, including their immune effects, have not been establ ished. We conducted a prospective? cross-sectional, observational mult icenter study of urban HD patients to determine the contribution of im munological factors to patient survival. We hypothesized increased pro inflammatory cytokines would be associated with increased mortality, a nd that improved immune function would be associated with survival. Me thods. Patients were assessed using demographic and anthropometric ind ices, Kt/V, protein catabolic rate (PCR) and immunologic variables inc luding circulating cytokine [interleukin (IL)-1, IL-2, IL-4, IL-5, IL- 6, IL-12, IL-13 and tumor necrosis factor (TNF)-alpha] levels, total h emolytic complement activity (CH50), and T cell number and function. A severity index, previously demonstrated to be a mortality marker, was used to grade medical comorbidity. A Cox proportional hazards model, controlling for patients' age, severity index, level of serum albumin concentration, dialyzer type and dialysis site was used to assess rela tive survival risk. Results. Two hundred and thirty patients entered t he study. The mean (+/- SD) age of the population was 54.4 +/- 14.2 ye ars, mean serum albumin concentration was 3.86 +/- 0.47 g/dl, mean PCR was 1.1 +/- 0.28 g/kg/day, and mean Kt/V 1.2 +/- 0.3. Patients' serum albumin concentration was correlated with levels of Kt/V and PCR, and their circulating IL-13 and TNF-ol levels, but negatively with their circulating IL-2 levels, T-cell number and T-cell antigen recall funct ion. T-cell antigen recall function correlated negatively with PCR, bu t not Kt/V. There was no correlation of any other immune parameter and medical or demographic factor. Immune parameters, however, were all h ighly intercorrelated. Mean level of circulating cytokines in HD patie nts were in all cases greater than those of a normal control group. Th ere were few differences in medical risk factors or immune parameters between patients treated with different types of dialyzers. After an a lmost three-year mean follow-up period, increased IL-1, TNF-alpha, IL- 6, and IL-13 levels were significantly associated with increased relat ive mortality risk, while higher levels of IL-2, IL-4, IL-5, IL-12, T- cell number and function, and CH50 were associated with improved survi val. The difference in survival between patients treated with unmodifi ed cellulose dialyzers and modified or synthetic dialyzers approached the level of statistical significance, but there were no differences i n levels of circulating cytokines between these two groups. Conclusion s. Higher levels of circulating proinflammatory cytokines are associat ed with mortality, while immune parameters reflecting improved T-cell function are associated with survival in ESRD patients treated with HD , independent of other medical risk factors. These factors may serve a s markers for outcome. The mechanism underlying the relationship of im mune function and survival, and the effect of interventions to normali ze immune function in HD patients should be studied.