Depression and nonadherence predict mortality in hemodialysis treated end‐stage renal disease patients

Depression has been identified as the most common psychiatric comorbidity in patients with end stage renal disease (ESRD) (1), with its' prevalence estimated at 20% to 30% (2). Depression has been associated with adverse medical outcomes, including mortality, for a variety of illnesses including cardiovascular disease (CVD) (3,4), diabetes (5–7), and cancer (8). Given the high prevalence of depression and its potential impact on health outcomes, researchers have looked at depression's impact on survival in the ESRD population. Investigations of the association between depression and mortality in ESRD patients receiving renal replacement therapy have produced mixed results (9). Early studies provided preliminary evidence that depression significantly predicts survival in hemodialysis (HD) patients, but these studies contained methodological limitations such as inadequate measurement of the construct and unrefined statistical analyses (10,11). Other studies failed to demonstrate an effect of depression on all-cause mortality in ESRD patients even when utilizing more valid measures of depression and more advanced statistical strategies that controlled for physical and demographic determinants of survival (12–14). More recently evidence has begun to accumulate to suggest that time-varying measurement of depression may better predict survival than a single assessment. Kimmel Peterson and Weihs et al. (15) were the first to demonstrate that persistent depressive affect is a risk factor for mortality in hemodialysis patients. In this study, Kimmel et al. (15) found that baseline depressive affect was not sufficient to predict mortality in a fairly large sample of HD patients, however, repeated measurements of depressive affect did predict survival in a time-varying model adjusted for illness co-morbidity and severity. These important results have since been replicated in larger samples using both self-report and structured physician interviews as means of assessing depressive affect and depression diagnosis (16, 17). The findings have also been extended to more specifically predict cardiovascular disease events as well as all-cause mortality while controlling for a wide range of covariates (18). While it appears that the duration of depression may affect survival in patients with ESRD, the impact of the severity of depression remains unclear. Early evidence suggests that severity of depression significantly predicts adverse health outcomes, with more severe depression being associated with increased risk for first hospitalization (19) and death (15). Given the ubiquity of untreated depression in the ESRD population and the gravity of the potential implications, further exploration is warranted to identify levels of depression that influence survival. The impact of depression on survival may be mediated by various psychological and physiological factors. Treatment non-adherence represents one potential pathway through which depression may affect mortality in patients with late stage kidney disease. Depressive symptoms of low motivation, impaired concentration, and apathy can significantly interfere with patients' adherence to treatment for ESRD. Studies (20, 21) have indicated a relationship between depressive affect and both laboratory and behavioral markers of poor compliance in dialysis patients. Decreased behavioral compliance with the dialysis prescription has been correlated with increased depressive affect in prevalent hemodialysis patients (22, 23, 24, 25, 26). This supporting data is suggestive of a mediational model in which treatment non-adherence partially explains the association between depression and mortality. In the current study, we explored the relationship between depressive affect and survival in a controlled, time-varying analysis. We examined the impact of depressive affect severity on mortality by dividing our sample into mild, moderate and severely depressed categories. Furthermore, as the relationship between depressive affect and mortality has been hypothesized to have various direct and indirect pathways including lack of self-care, we also tested whether self-reported medication adherence plays a predictive role in HD survival (2). It is possible that depressed mood leads to lack of adherence with specific aspects of the dialysis prescription, which may be the cause of the decreased survival.