Rationale : Patients with end-stage renal disease are characterized by increased cardiovascular and all-cause mortality because of advanced remodeling of the macrovascular and microvascular beds. Objective : The aim of this study was to determine whether retinal microvascular function can predict all-cause and cardiovascular mortality in patients with end-stage renal disease. Methods and Results : In the multicenter prospective observational ISAR study (Risk Stratification in End-Stage Renal Disease), data on dynamic retinal vessel analysis were available in a subcohort of 214 dialysis patients (mean age, 62.6±15.0; 32% women). Microvascular dysfunction was quantified by measuring maximum arteriolar dilation and maximum venular dilation (vMax) of retinal vessels in response to flicker light stimulation. During a mean follow-up of 44 months, 55 patients died, including 25 cardiovascular and 30 noncardiovascular fatal events. vMax emerged as a strong independent predictor for all-cause mortality. In the Kaplan-Meier analysis, individuals within the lowest tertile of vMax showed significantly shorter 3-year survival rates than those within the highest tertile (66.9±5.8% versus 92.4±3.3%). Univariate and multivariate hazard ratios for all-cause mortality per SD increase of vMax were 0.62 (0.47–0.82) and 0.65 (0.47–0.91), respectively. Maximum arteriolar dilation and vMax were able to significantly predict nonfatal and fatal cardiovascular events (hazard ratio, 0.74 [0.57–0.97] and 0.78 [0.61–0.99], respectively). Conclusions : Our results provide the first evidence that impaired retinal venular dilation is a strong and independent predictor of all-cause mortality in hemodialyzed end-stage renal disease patients. Dynamic retinal vessel analysis provides added value for prediction of all-cause mortality and may be a novel diagnostic tool to optimize cardiovascular risk stratification in end-stage renal disease and other high-risk cardiovascular cohorts. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01152892.

Background Evidence on the utility of ambulatory BP monitoring for risk prediction has been scarce and inconclusive in patients on hemodialysis. In addition, in cardiac diseases such as heart failure and atrial fibrillation (common among patients on hemodialysis), studies have found that parameters such as systolic BP (SBP) and pulse pressure (PP) have inverse or nonlinear (U-shaped) associations with mortality. Methods In total, 344 patients on hemodialysis (105 with atrial fibrillation, heart failure, or both) underwent ambulatory BP monitoring for 24 hours, starting before a dialysis session. The primary end point was allcause mortality; the prespecified secondary end point was cardiovascular mortality. We performed linear and nonlinear Cox regression analyses for risk prediction to determine the associations between BP and study end points. Results During the mean 37.6-month follow-up, 115 patients died (47 from a cardiovascular cause). SBP and PP showed a U-shaped association with all-cause and cardiovascular mortality in the cohort. In linear subgroup analysis, SBP and PP were independent risk predictors and showed a significant inverse relationship to all-cause and cardiovascular mortality in patients with atrial fibrillation or heart failure. In patients without these conditions, these associations were in the opposite direction. SBP and PP were significant independent risk predictors for cardiovascular mortality; PP was a significant independent risk predictor for all-cause mortality. Conclusions This study provides evidence for the U-shaped association between peripheral ambulatory SBP or PP and mortality in patients on hemodialysis. Furthermore, it suggests that underlying cardiac disease can explain the opposite direction of associations.

Background: Although low magnesium levels have been associated with an increased mortality in dialysis patients, they are kept low by routinely-used dialysates containing 0.50 mmol/L magnesium. Thus, we investigated the impact of a higher dialysate magnesium concentration on mortality. Methods: 25 patients on high dialysate magnesium (HDM) of 0.75 mmol/L were 1:2 matched to 50 patients on low dialysate magnesium (LDM) of 0.50 mmol/L and followed up for 3 years with regards to all-cause and cardiovascular mortality. Patients were matched according to age, gender, a modified version of the Charlson Comorbidity Index (CCI), and smoking status. Results: During the follow-up period, five patients died in the HDM and 18 patients in the LDM group. Patients in the HDM group had significantly higher ionized serum magnesium levels than matched controls (0.64 ± 0.12 mmol/L vs. 0.57 ± 0.10 mmol/L, p = 0.034). Log rank test showed no difference between treatment groups for all-cause mortality. After adjustment for age and CCI, Cox proportional hazards regression showed that HDM independently predicted a 65% risk reduction for all-cause mortality (hazard ratio 0.35, 95% confidence interval [CI]: 0.13, 0.97). Estimated 3-year probability of death from a cardiovascular event was 14.5% (95% CI: 7.9, 25.8) in the LDM group vs. 0% in the HDM group. Log rank test found a significant group difference for cardiovascular mortality (χ2 = 4.15, p = 0.042). Conclusions: Our data suggests that there might be a beneficial effect of an increased dialysate magnesium on cardiovascular mortality in chronic dialysis patients.