Jennifer E. Flythe

Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality

Patients receiving hemodialysis have high rates of cardiovascular morbidity and mortality that may be related to the hemodynamic effects of rapid ultrafiltration. Here we tested whether higher dialytic ultrafiltration rates are associated with greater all-cause and cardiovascular mortality, and hospitalization for cardiovascular disease. We used data from the Hemodialysis Study, an almost-7-year randomized clinical trial of 1846 patients receiving thrice-weekly chronic dialysis. The ultrafiltration rates were divided into three categories: up to 10 ml/h/kg, 10-13 ml/h/kg, and over 13 ml/h/kg. Compared to ultrafiltration rates in the lowest group, rates in the highest were significantly associated with increased all-cause and cardiovascular-related mortality with adjusted hazard ratios of 1.59 and 1.71, respectively. Overall, ultrafiltration rates between 10-13 ml/h/kg were not associated with all-cause or cardiovascular mortality; however, they were significantly associated among participants with congestive heart failure. Cubic spline interpolation suggested that the risk of all-cause and cardiovascular mortality began to increase at ultrafiltration rates over 10 ml/h/kg regardless of the status of congestive heart failure. Hence, higher ultrafiltration rates in hemodialysis patients are associated with a greater risk of all-cause and cardiovascular death.

Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

Factors associated with intradialytic systolic blood pressure variability.

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.

A Model of Systolic Blood Pressure During the Course of Dialysis and Clinical Factors Associated With Various Blood Pressure Behaviors

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.

Intradialytic Blood Pressure Abnormalities: The Highs, The Lows and All That Lies Between.

Background: Frequent blood pressure (BP) measurements are necessary to ensure patient safety during hemodialysis treatments. Intradialytic BPs are not optimal tools for hypertension diagnosis and cardiovascular risk stratification, but they do have critical clinical and prognostic significance. We present evidence associating intradialytic BP phenomena including fall, rise and variability with adverse clinical outcomes and review related pathophysiologic mechanisms and potential management strategies. Summary: Observational studies demonstrate associations between intradialytic hypotension, hypertension and BP variability and mortality. Lack of consensus regarding diagnostic criteria has hampered data synthesis, and prospective studies investigating optimal management strategies for BP phenomena are lacking. Mechanistic data suggest that cardiac, gut, kidney and brain ischemia may lie on the causal pathway between intradialytic hypotension and mortality, and endothelial cell dysfunction, among other factors, may be an important mediator of intradialytic hypertension and adverse outcomes. These plausible pathophysiologic links present potential therapeutic targets for future inquiry. The phenomenon of intradialytic BP variability has not been adequately studied, and practical clinical measures and treatment strategies are lacking. Key Messages: Intradialytic BP phenomena have important prognostic bearing. Clinical practice guidelines for both intradialytic hypotension and hypertension exist, but their underlying evidence is weak overall. Further research is needed to develop consensus diagnostic criteria for intradialytic hypotension, hypertension and BP variability and to elucidate optimal treatment and prevention strategies for each BP manifestation.

The Risks of High Ultrafiltration Rate in Chronic Hemodialysis: Implications for Patient Care

As dialytic practice has evolved, hemodialysis (HD) adequacy has come to be defined in terms of small molecule clearance. A growing body of evidence suggests that fluid dynamics, specifically ultrafiltration rate (UFR), bear clinical and physiological significance and should perhaps play a more central role in titrating HD therapy. Three recent studies have shown an independent association between higher UFR and mortality. Further work is needed to determine whether this relationship represents a direct toxic effect of rapid fluid perturbations or whether this association is a consequence of confounding on the basis of large interdialytic weight gain, as each would prompt a different therapeutic response. This mounting evidence builds the case that fluid management should play a more central role in the dialytic prescription and that more individualized approaches to fluid management should be encouraged.

Outcomes after the Long Interdialytic Break: Implications for the Dialytic Prescription

A thrice‐weekly schedule dominates hemodialysis practice today. Inherent in such a schedule is a 72‐hour interweek break over the weekend. A growing body of evidence suggests that this break may be associated with increased cardiovascular morbidity and mortality. Five recent studies have linked dialysis session timing to higher cardiovascular event rates, and have shed light on possible underlying physiologic mechanisms. We reviewed outcome data linking the “long break” to cardiovascular outcomes, and suggest physiologic rationale for this relationship while identifying knowledge gaps that require further study to inform discussions regarding the application and composition of individualized dialysis prescriptions. Further work is needed to determine the relative importance of electrolyte perturbations and hemodynamic shifts in the relationship between the long break and cardiovascular mortality. The evidence suggests that at least in some at‐risk patients, an individualized approach to the dialytic schedule and prescription is warranted.

Blood pressure variability among chronic dialysis patients: recent advances in knowledge.

Purpose of reviewThis review focuses on recent evidence linking blood pressure variability (BPV) to adverse clinical outcomes in the chronic hemodialysis patient population. Recent findingsBPV is an increasingly recognized poor prognostic factor in the general population. A growing body of evidence suggests that both short-term and long-term BPV are associated with adverse events among chronic dialysis patients. Over the last 18 months, several studies have linked long-term BPV (considered dialysis treatment to dialysis treatment) to all-cause and cardiovascular morbidity and mortality. Similar results have been demonstrated for short-term (considered as intradialytic) BPV and clinical outcomes. Further studies substantiating these findings and examining potential BPV mitigation strategies are needed. Additionally, a BPV metric that is easily calculated and tracked in the clinical setting is necessary before BPV can become a routine component of clinical monitoring. SummaryRecent observational data demonstrate an association between short-term and long-term BPV and adverse outcomes among chronic hemodialysis patients. Further research is needed to identify strategies that mitigate this risk and to translate these findings into clinical practice.

Psychosocial Factors and 30-Day Hospital Readmission among Individuals Receiving Maintenance Dialysis: A Prospective Study

Background: Thirty-day hospital readmissions are common among maintenance dialysis patients. Prior studies have evaluated easily measurable readmission risk factors such as comorbid conditions, laboratory results, and hospital discharge day. We undertook this prospective study to investigate the associations between hospital-assessed depression, health literacy, social support, and self-rated health (separately) and 30-day hospital readmission among dialysis patients. Methods: Participants were recruited from the University of North Carolina Hospitals, 2014-2016. Validated depression, health literacy, social support, and self-rated health screening instruments were administered during index hospitalizations. Multivariable logistic regression models with 30-day readmission as the dependent outcome were used to examine readmission risk factors. Results: Of the 154 participants, 58 (37.7%) had a 30-day hospital readmission. In unadjusted analyses, individuals with positive screening for depression, lower health literacy, and poorer social support were more likely to have a 30-day readmission (vs. negative screening). Positive depression screening and poorer social support remained significantly associated with 30-day readmission in models adjusted for race, heart failure, admitting service, weekend discharge day, and serum albumin: adjusted OR (95% CI) 2.33 (1.02-5.15) for positive depressive symptoms and 2.57 (1.10-5.91) for poorer social support. The area under the receiver operating characteristic curve (AUC) of the multivariable model adjusted for social support status was significantly greater than the AUC of the multivariable model without social support status (test for equality; p value = 0.04). Conclusion: Poor social support and depressive symptoms identified during hospitalizations may represent targetable readmission risk factors among dialysis patients. Our findings suggest that hospital-based assessments of select psychosocial factors may improve readmission risk prediction.

Establishing a Core Outcome Measure for Fatigue in Patients on Hemodialysis: A Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) Consensus Workshop Report

Fatigue is one of the most highly prioritized outcomes for patients and clinicians, but remains infrequently and inconsistently reported across trials in hemodialysis. We convened an international Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) consensus workshop with stakeholders to discuss the development and implementation of a core outcome measure for fatigue. 15 patients/caregivers and 42 health professionals (clinicians, researchers, policy makers, and industry representatives) from 9 countries participated in breakout discussions. Transcripts were analyzed thematically. 4 themes for a core outcome measure emerged. Drawing attention to a distinct and all-encompassing symptom was explicitly recognizing fatigue as a multifaceted symptom unique to hemodialysis. Emphasizing the pervasive impact of fatigue on life participation justified the focus on how fatigue severely impaired the patients ability to do usual activities. Ensuring relevance and accuracy in measuring fatigue would facilitate shared decision making about treatment. Minimizing burden of administration meant avoiding the cognitive burden, additional time, and resources required to use the measure. A core outcome measure that is simple, is short, and includes a focus on the severity of the impact of fatigue on life participation may facilitate consistent and meaningful measurement of fatigue in all trials to inform decision making and care of patients receiving hemodialysis.