Background Although blood pressure lability during hemodialysis has long been recognized, little is known about factors that promote nonsystematic intradialytic blood pressure variability. Study ...Design Prospective observational cohort. Setting & Participants Random cluster sample of 218 prevalent hemodialysis patients treated at 5 participating DaVita Dialysis units. Predictors Clinical variables that may plausibly influence intradialytic systolic blood pressure (SBP) variability. Outcomes SBP variability as described by: (1) the deviation of SBP from its anticipated course (primary metric) and (2) the absolute value of the difference between successive SBP measurements (secondary metric). Measurements SBPs measured and recorded (n = 19,170) per clinical protocol during hemodialysis treatments (n = 2,422; median 11 per patient) occurring in the first 30 days of study. Predictors were assessed through standardized interview, examination, and medical record abstraction. Results Results were similar when SBP variability was considered in terms of the primary and secondary metrics. Older age and longer dialysis vintage were associated with increased SBP variability, whereas other patient characteristics were not. Greater fluid removal during hemodialysis (whether considered as volume or rate either absolute or relative to total-body water) was associated with greater SBP variability independently of its effects on net pre- to posttreatment SBP reduction. Neither number nor dialyzability of antihypertensive medications nor individual classes of agents showed an association with SBP variability. Limitations Over-representation of African Americans and patients with congestive heart failure; observational design; use of clinically measured blood pressures; absence of medication adherence confirmation. Conclusions Increased intradialytic SBP variability is associated with greater dialytic fluid removal and rate, as well as demographic characteristics, such as older age and dialysis vintage. Further work is needed to confirm these findings and measure associations between SBP variability and clinical outcomes.
Background Little is known about the behavior of systolic blood pressure (SBP) during hemodialysis. Study Design Prospective observational cohort. Setting & Participants 218 prevalent hemodialysis ...patients treated at 5 participating DaVita Dialysis units. Predictors Clinical variables that may plausibly influence the behavior of SBP during the course of hemodialysis sessions. Outcomes SBP at the onset of dialysis and its rate of change (slope) over the first 25% and latter 75% of the treatment interval. Measurements SBPs measured and recorded per clinical protocol during the first 30 days of study (median, 11 treatments/patient; SBP measured at 30-minute intervals). Results Intradialytic SBP behavior is well characterized by a 2-slope linear spline model, which describes SBP at time zero, a rapid decrease during the first 25% of the treatment (early), and a more gradual decrease thereafter (late). Higher ultrafiltration volume and rate each are associated with greater SBP at the start of dialysis and more rapid early and late SBP decreases. Use of a higher number of antihypertensives was associated with greater time zero SBP. Calcium acetate use is associated with high SBP at the start of hemodialysis and a more pronounced decrease during the early and late parts of treatment. Limitations Over-representation of blacks and patients with congestive heart failure; observational design; use of clinically measured blood pressures. Conclusions Intradialytic SBP can be characterized using 3 parameters: value at the start of dialysis and slopes during the first 25% and latter 75% of treatment. Practices related to fluid management, antihypertensive use, and metabolic bone disease control are associated with blood pressure behavior during dialysis. Further work is needed to confirm findings and measure associations between various aspects of intradialytic blood pressure behavior and clinical outcomes.
Background Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid ...electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. Study Design Prospective cohort study. Setting & Participants 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). Predictor Dialysate potassium concentration at study entry. Outcomes Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. Results During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 95% CI, 0.91-1.01 for mortality and 0.98 95% CI, 0.88-1.08 for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 95% CI, 0.05-0.14 mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). Limitations Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. Conclusions In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.
Addressing fluid intake and volume control requires alignment and coordination of patients, providers, dialysis facilities, and payers, potentially necessitating a “Volume First” approach. This ...article reports the consensus opinions achieved at the March 2013 symposium of the Chief Medical Officers of 14 of the largest dialysis providers in the United States. These opinions are based on broad experience among participants, but often reinforced by only observational and frequently retrospective studies, highlighting the lack of high-quality clinical trials in nephrology. Given the high morbidity and mortality rates among dialysis patients and the absence of sufficient trial data to guide most aspects of hemodialysis therapy, participants believed that immediate attempts to improve care based on quality improvement initiatives, physiologic principles, and clinical experiences are warranted until such time as rigorous clinical trial data become available. The following overarching consensus opinions emerged. (1) Extracellular fluid status should be a component of sufficient dialysis, such that approaching normalization of extracellular fluid volume should be a primary goal of dialysis care. (2) Fluid removal should be gradual and dialysis treatment duration should not routinely be less than 4 hours without justification based on individual patient factors. (3) Intradialytic sodium loading should be avoided by incorporating dialysate sodium concentrations set routinely in the range of 134-138 mEq/L, avoidance of routine use of sodium modeling, and avoidance of hypertonic saline solution. (4) Dietary counseling should emphasize sodium avoidance.
Background Hyperkalemia is common among hemodialysis patients and is associated with morbidity and mortality. The long interdialytic interval is likewise associated with adverse outcomes. However, ...the interplay among serum potassium, dialysis cycle phase, and clinical outcomes has not been examined. Study Design Retrospective observational study. Setting & Participants 52,734 patients receiving in-center hemodialysis at a large dialysis organization during 2010 and 2011 contributed 533,889 potassium measurements (230,634 on Monday; 285,522 on Wednesday; 17,733 on Friday). Predictor Serum potassium concentration, day of the week of potassium measurement. Outcomes Death, hospitalization, emergency department (ED) visit. Results There was a significant association between higher serum potassium and risk of hospitalization within 96 hours that was of greater magnitude on Fridays (389 hospitalizations) than Mondays or Wednesdays (4,582 and 4,629 hospitalizations, respectively; P for interaction = 0.008). Serum potassium of 5.5 to <6.0 (vs the referent category of 4.0-<4.5 mEq/L) was associated with increased risk of hospitalization on Fridays, with an adjusted OR of 1.68 (95% CI, 1.22-2.30). However, serum potassium of 5.5 to <6.0 mEq/L was associated with only mild elevation of risk on Mondays and no significantly increased risk on Wednesdays (adjusted ORs of 1.12 95% CI, 1.00-1.24 and 1.04 95% CI, 0.94-1.16, respectively). Associations of elevated serum potassium (6.0-<6.5 mEq/L or greater) with death and ED visit were significant, but did not differ based on day of the week. Limitations There were insufficient observations to detect effect modification by day of the week for deaths, ED visits, and specific causes of hospitalizations. Confounding may have influenced results. Conclusions Higher serum potassium is associated with increased short-term risk of hospitalization, ED visit, and death. The association between serum potassium and hospitalization risk is modified by day of the week, consistent with a contribution of accumulated potassium to adverse outcomes following the long interdialytic interval. Further work is needed to determine whether directed interventions ameliorate this risk.
Background Blood pressure variability (BPV) is one putative risk factor for cardiovascular disease and mortality in hemodialysis patients. The purposes of this study are to identify a suitable metric ...of long-term BPV in this population and determine whether an association between BPV and all-cause mortality exists. Study Design Retrospective cohort study. Settings & Participants Patients from the Accelerated Mortality on Renal Replacement (ArMORR) cohort who were adult, incident to hemodialysis at any Fresenius Medical Care unit between June 2004 and August 2005, and had suitable blood pressure data were studied (n = 6,961). Predictor Predialysis blood pressures measured between dialysis days 91 and 180 were used to determine each patient's absolute level of, trend in (slope over time), and variability in blood pressure. Outcome All-cause mortality beginning immediately after day 180 and continuing through day 365 or until censoring (median follow-up, 185 days). Results Of the 4 candidate BPV metrics, only average residual-intercept ratio adequately distinguished BPV from absolute blood pressure level and temporal blood pressure trend. In the primary analysis, each SD increase in systolic and diastolic BPV was associated with adjusted hazard ratios for all-cause mortality of 1.13 (95% confidence interval, 1.03 to 1.23) and 1.15 (95% confidence interval, 1.06 to 1.26), respectively. Results were consistent across multiple sensitivity analyses in which inclusion and exclusion criteria and timing of blood pressure measurements were varied. Limitations Contingency of results on the validity of mathematic description of BPV; potential for misclassification bias and residual confounding. Conclusions Provided the mathematical descriptions of BPV are valid, the data suggest that systolic and diastolic BPV is associated with all-cause mortality in incident hemodialysis patients. Additional study is necessary to confirm and generalize findings, assess the interplay between systolic and diastolic BPV, and assess causality.
Background In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with ...higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. Study Design We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. Setting & Participants 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. Predictor Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4 mg/dL). Outcome All-cause mortality. Results 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0 mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4 mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0 mg/dL were 1.39 (95% CI, 1.23-1.58; P < 0.001) and 1.20 (95% CI, 1.06-1.36; P = 0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5 g/dL) and magnesium level < 2.0 mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P = 0.004), whereas patients with high serum albumin levels (≥3.5 g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 P ≤ 0.001 for magnesium < 2.0 and ≥2.0 mg/dL, respectively; reference: albumin < 3.5 g/dL and magnesium ≥ 2.0 mg/dL). Limitations Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. Conclusions Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.
Background l -Carnitine is an endogenous compound thought to be helpful in treating patients with dialysis-related hypotension and muscle cramps; however, sufficient evidence for these indications is ...lacking. Study Design Systematic review and meta-analysis. Setting & Population Adult patients with end-stage renal disease receiving long-term hemodialysis. Selection Criteria for Studies All published English-language reports of randomized placebo-controlled trials of l -carnitine supplementation in adult long-term hemodialysis patients. Intervention Supplemental l -carnitine (or placebo) for at least 8 weeks. Outcome Random-effects pooled odds ratio for intradialytic cramping or hypotension in l -carnitine–treated participants. Results Of 317 potentially relevant articles, 7 (total enrollment of 193 patients) met criteria for inclusion. Four articles reported results for both hypotension and cramps, 1 had results for only hypotension, and 2 reported results for only cramps. Using data from all 6 relevant trials, the pooled odds ratio for cramping after l -carnitine supplementation was 0.30 (95% confidence interval, 0.09 to 1.00; P = 0.05). Analysis of the 5 studies examining the response of intradialytic hypotension to l -carnitine supplementation yielded a pooled odds ratio of 0.28 (95% confidence interval, 0.04 to 2.23; P = 0.2). Limitations The small number of available studies yielded limited statistical power. In addition, there was considerable interstudy heterogeneity. Conclusions Although suggestive in the case of muscle cramping, the available evidence does not confirm a beneficial effect of l -carnitine supplementation on dialysis-related muscle cramping or intradialytic hypotension. Additional study in the form of large rigorous randomized trials is needed in both cases.
Background Hemodialysis (HD) access is considered a critical and actionable determinant of morbidity, with a growing literature suggesting that initial HD access type is an important marker of ...long-term outcomes. Accordingly, we examined HD access during the incident dialysis period, focusing on infection risk and successful fistula creation during the first dialysis year. Study Design Longitudinal cohort. Setting & Participants All US adults admitted to Fresenius Medical Care North America facilities within 15 days of first maintenance dialysis session between January 1 and December 31, 2007. Predictor Vascular access type at HD therapy initiation. Outcomes Vascular access type at 90 days and at the end of the first year on HD therapy, bloodstream infection within the first year by access type, and catheter complication rate. Results Of 25,003 incident dialysis patients studied, 19,622 (78.5%) initiated dialysis with a catheter; 4,151 (16.6%), with a fistula; and 1,230 (4.9%), with a graft. At 90 days, 14,105 (69.7%) had a catheter, 4,432 (21.9%) had a fistula, and 1,705 (8.4%) had a graft. Functioning fistulas and grafts at dialysis therapy initiation had first-year failure rates of 10% and 15%, respectively. Grafts were seldom replaced by fistulas (3%), whereas 7,064 (47.6%) of all patients who initiated with a catheter alone still had only a catheter at 1 year. Overall, 3,327 (13.3%) patients had at least one positive blood culture during follow-up, with the risk being similar between the fistula and graft groups, but approximately 3-fold higher in patients with a catheter ( P <0.001 for either comparison). Nearly 1 in 3 catheters (32.5%) will require tissue plasminogen activator use by a median of 41 days, with 59% requiring more than one tissue plasminogen activator administration. Limitations Potential underestimation of bacteremia because follow-up blood culture results did not include samples sent to local laboratories. Conclusions In a large and representative population of incident US dialysis patients, catheter use remains very high during the first year of HD care and is associated with high mechanical complication and bloodstream infection rates.
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