Shorter length dialysis sessions are associated with increased mortality, independent of body weight

Hemodialysis patients have high rates of mortality that may be related to aspects of the dialytic procedure. In prior studies, shorter length dialysis sessions have been associated with decreased survival, but these studies may have been confounded by body size differences. Here we tested whether in-center thrice-weekly hemodialysis patients with adequate urea clearances but shorter dialysis session length is associated with mortality independent of body size. Data were taken from a large national cohort of patients from a large dialysis organization undergoing thrice-weekly, in-center hemodialysis. In the primary analysis, patients with prescribed dialysis sessions greater and less than 240 minutes were pair-matched on post-dialysis weight as well as on age, gender, and vascular access type. Compared to prescribed longer dialysis sessions, session lengths less than 240 minutes were significantly associated with increased all-cause mortality (adjusted hazard ratio 1.26). The association was consistent across strata of age, gender, and dialysis post-weight. Secondary analyses found a dose-response between prescribed session length and survival. Thus, among patients with adequate urea clearance, shorter dialysis session lengths are associated with increased mortality independent of body weight

Association of Continuation of Loop Diuretics at Hemodialysis Initiation with Clinical Outcomes

BACKGROUND AND OBJECTIVES: Loop diuretics are commonly used to manage nondialysis-dependent CKD. Despite benefits of augmented urine output, loop diuretics are often discontinued after dialysis initiation. Here, we assessed the association of the early decision to continue loop diuretics at hemodialysis start with clinical outcomes during the first year of dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We considered all patients on in-center hemodialysis at a large dialysis organization (2006-2013) with Medicare Part A and D benefits who had an active supply of a loop diuretic at dialysis initiation (n=11,297). Active therapy was determined on the basis of whether loop diuretic prescription was refilled after dialysis initiation and within 30 days of exhaustion of prior supply. Patients were followed under an intention-to-treat paradigm for up to 12 months for rates of death, hospitalization, and intradialytic hypotension and mean monthly values of interdialytic weight gain, serum potassium, predialysis systolic BP, and ultrafiltration rates. RESULTS: We identified 5219 patients who refilled a loop diuretic and 6078 eligible controls who did not. After adjustments for patient mix and clinical differences, continuation of loop diuretics was associated with lower hospitalization (adjusted incidence rate ratio, 0.93; 95% confidence interval, 0.89 to 0.98) and intradialytic hypotension (adjusted incidence rate ratio, 0.95; 95% confidence interval, 0.92 to 0.99) rates, no difference in death rate (adjusted hazard ratio, 0.92; 95% confidence interval, 0.84 to 1.01), and lower interdialytic weight gain (P=0.03). CONCLUSIONS: Continuation of loop diuretics after hemodialysis initiation was associated with lower rates of hospitalization and intradialytic hypotension as well as lower interdialytic weight gain, but there was no difference in mortality over the first year of dialysis

Dialysate sodium, serum sodium and mortality in maintenance hemodialysis

Abstract Background. Individuals with end-stage kidney disease appear to have stable pre-dialysis serum sodium concentrations over time, with lower values associating with increased mortality. Dialysate sodium concentrations have increased over many years in response to shorter treatments, but the relationship between serum sodium, dialysate sodium and outcomes in chronic hemodialysis patients has not yet been systematically examined. Methods. We studied a cohort of 2272 individuals receiving thrice-weekly hemodialysis treatment. Available data included demographics, laboratory and clinical measures, details of the dialysis prescription and 30-month follow-up. We examined the distribution of serum and dialysate sodium among subjects and compared mortality according to dialysate and serum sodium concentrations using Cox regression models. Results. Dialysate sodium concentration varied within and among dialysis centers. The pre-dialysis serum sodium concentration (mean 136.1 mmol/L) did not differ across dialysate sodium concentrations. There was evidence for effect modification for mortality according to differing serum sodium and dialysate sodium concentrations (P ¼ 0.05). For each 4 mmol/L increment in serum sodium, the hazard ratio for death was 0.72 [95% confidence interval (CI) 0.63-0.81] with lower dialysate sodium compared to 0.86 (95% CI 0.75-0.99) for higher dialysate sodium. Higher dialysate sodium concentration was associated with mortality at higher, but not lower, pre-dialysis serum sodium concentrations. Conclusions. The pre-dialysis serum sodium concentration appears to be unaffected by the dialysate sodium concentration. The relationship between serum and dialysate sodium and mortality appears to be variable. Further research is warranted to determine the biological mechanisms of these associations and to re-examine total body sodium handling in hemodialysis

Ultrafiltration-profiled hemodialysis to reduce dialysis-related cardiovascular stress: Study protocol for a randomized controlled trial

Rapid fluid removal (ultrafiltration, UF) is associated with higher cardiovascular morbidity and mortality among individuals receiving maintenance hemodialysis (HD). Fluid removal rates that exceed vascular refill rates can result in hemodynamic instability, end-organ damage to the heart, kidneys, gut and brain, among other organs, and patient symptoms. There are no known evidence-based HD treatment strategies to reduce harm from higher UF rates. Ultrafiltration profiling, the practice of varying UF rates to maximize fluid removal during periods of greatest hydration and plasma oncotic pressure, has been proposed as an HD treatment intervention that may reduce UF rate-related complications. This study is a randomized 4-phase cross-over trial in which participants are successively alternated between study arms with intervening washout periods, and treatment order is randomized. After 4-week screening and 6-week baseline periods, participants are randomized to HD with conventional UF or HD with UF profiling for a period of 3 weeks followed by a 1-week washout period before crossing over. Participants cross into conventional UF and UF profiling phases twice (2 phases per arm). The primary outcomes of interest are intradialytic hypotension (nadir intradialytic systolic blood pressure <90-mmHg), pre-to post-HD change in troponin T (expressed as a percentage), change in left ventricular global longitudinal strain (an echocardiographic measure of left ventricular systolic function), and development of intradialytic left ventricular stunning (worsening of contractile function in ≥2 segments). This study will determine the impact of UF profiling on UF rate-related cardiovascular complications in prevalent, maintenance HD patients

Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial

BackgroundMore rapid fluid removal during hemodialysis is associated with adverse cardiovascular outcomes and longer dialysis recovery times. The effect of ultrafiltration (UF) profiling, independent of concomitant sodium profiling, on markers of intradialytic hemodynamics and other outcomes has been inadequately studied.MethodsFour-phase, blinded crossover trial. Participants (UF rates>10 mL/h/kg) were assigned in random order to receive hemodialysis with UF profiling (constantly declining UF rate, intervention) vs. hemodialysis with conventional UF (control). Each 3-week 9-treatment period was followed by a 1-week 3-treatment washout period. Participants crossed into each study arm twice (2 phases/arm); 18 treatments per treatment type. The primary outcomes were intradialytic hypotension, pre- to post-dialysis troponin T change, and change from baseline in left ventricular global longitudinal strain. Other outcomes included intradialytic symptoms and blood volume measured-plasma refill (post-dialysis volume status measure), among others. Each participant served as their own control.ResultsOn average, the 34 randomized patients (mean age 56 years, 24% female, mean dialysis vintage 6.3 years) had UF rates>10 mL/h/kg in 56% of treatments during the screening period. All but 2 patients completed the 15-week study (prolonged hospitalization, kidney transplant). There was no significant difference in intradialytic hypotension, troponin T change, or left ventricular strain between hemodialysis with UF profiling and conventional UF. With UF profiling, participants had significantly lower odds of light-headedness and plasma refill compared to hemodialysis with conventional UF.ConclusionsUltrafiltration (UF) profiling did not reduce the odds of treatment-related cardiac stress but did reduce the odds of light-headedness and post-dialysis hypervolemia.Trial registrationClinicaltrials.gov identifier: NCT03301740 (registered October 4, 2017

Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients.

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined

Identification of volume overload hospitalizations among hemodialysis patients using administrative claims: a validation study

Abstract Background High rates of volume overload hospitalizations may indicate inadequate dialysis facility fluid management. Administrative claims databases are often used to study such outcomes, but these data are generated for billing purposes and may not capture clinical nuance. It is unknown if volume overload admissions can be correctly identified in administrative data and if a single claims-based definition for volume overload can be used across epidemiologic surveillance studies, observational studies of exposure-outcome associations and quality assessments. We conducted a validation study to assess the accuracy of claims-based definitions for volume overload hospitalizations among hemodialysis patients. Methods Data were taken from a random sample of 315 adult hemodialysis patients admitted to University of North Carolina Hospitals from January 2010 through June 2013. Standardized chart reviews were conducted to clinically adjudicate the presence or absence of volume overload at hospital admission. Claims-based definitions were constructed from varying combinations of fluid-related ICD-9 discharge diagnosis codes including fluid overload, pulmonary edema, pleural effusion, and heart failure. Using clinically adjudicated volume overload hospitalizations as the reference standard, validity metrics and their 95 % confidence intervals (CIs) were estimated for each definition. Results Of the 315 hospital admissions, 77 (24.4 %) were clinically adjudicated as volume overload hospitalizations. The prevalence of claims-identified volume overload admissions varied across definitions, ranging from 1.6 to 37.1 %. When definitions were constructed with discharge diagnosis codes present in any billing position, volume overload hospitalizations defined by fluid overload, pleural effusion or heart failure diagnosis codes had the highest sensitivity, 81.8 % (95 % CI: 71.4 %, 89.7 %). Volume overload hospitalizations defined by pulmonary edema diagnosis codes had the highest specificity, 98.3 % (95 % CI: 95.8 %, 99.5 %). Definitions constructed with discharge diagnosis codes present in any billing position (versus the primary position) captured more false positive events. Conclusions Prevalence and validity estimates of volume overload hospitalizations vary across claims-based definitions. A universal claims-based definition for volume overload hospitalizations may not apply to all clinical and research scenarios. Investigators and regulators need to consider the implications of misclassifying events when evaluating and monitoring hemodialysis patient volume overload admissions with administrative data. Claims-based definitions should be selected accordingly

Thyroid Status and Death Risk in US Veterans With Chronic Kidney Disease.

OBJECTIVE:Given that patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) have a disproportionately higher prevalence of hypothyroidism compared with their non-CKD counterparts, we sought to determine the association between thyroid status, defined by serum thyrotropin (TSH) levels, and mortality among a national cohort of patients with NDD-CKD. PATIENTS AND METHODS:Among 227,422 US veterans with stage 3 NDD-CKD with 1 or more TSH measurements during the period October 1, 2004, to September 30, 2012, we first examined the association of thyroid status, defined by TSH categories of less than 0.5, 0.5 to 5.0 (euthyroidism), and more than 5.0 mIU/L, with all-cause mortality. We then evaluated 6 granular TSH categories: less than 0.1, 0.1 to less than 0.5, 0.5 to less than 3.0, 3.0 to 5.0, more than 5.0 to 10.0, and more than 10.0 mIU/L. We concurrently examined thyroid status, thyroid-modulating therapy, and mortality in sensitivity analyses. RESULTS:In expanded case-mix adjusted Cox analyses, compared with euthyroidism, baseline and time-dependent TSH levels of more than 5.0 mIU/L were associated with higher mortality (adjusted hazard ratios [aHRs] [95% CI], 1.19 [1.15-1.24] and 1.23 [1.19-1.28], respectively), as were baseline and time-dependent TSH levels of less than 0.5 mIU/L (aHRs [95% CI], 1.18 [1.15-1.22] and 1.41 [1.37-1.45], respectively). Granular examination of thyroid status showed that incrementally higher TSH levels of 3.0 mIU/L or more were associated with increasingly higher mortality in baseline and time-dependent analyses, and TSH categories of less than 0.5 mIU/L were associated with higher mortality (reference, 0.5-<3.0 mIU/L) in baseline analyses. In time-dependent analyses, untreated and undertreated hypothyroidism and untreated hyperthyroidism were associated with higher mortality (reference, spontaneous euthyroidism), whereas hypothyroidism treated-to-target showed lower mortality. CONCLUSION:Among US veterans with NDD-CKD, high-normal TSH (≥3.0 mIU/L) and lower TSH (<0.5 mIU/L) levels were associated with higher death risk. Interventional studies identifying the target TSH range associated with the greatest survival in patients with NDD-CKD are warranted

Serum albumin and hospitalization among pediatric patients with end-stage renal disease who started dialysis therapy.

BackgroundHypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis.MethodsIn a retrospective cohort study of children 1-17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007-2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model.ResultsAmong 416 eligible patients, median (interquartile range) age was 14 (10-16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9-2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2-3.2), 1.9 (1.5-2.4), 1.6 (1.3-1.9), and 2.7 (1.7-3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5- < 4.0, 4.0- < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24-2.13), 1.32 (1.10-1.58), and 1.25 (1.06-1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation.ConclusionsBoth high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made