Extended-hours hemodialysis is associated with lower mortality risk in patients with end-stage renal disease
2016; Elsevier BV; Volume: 90; Issue: 6 Linguagem: Inglês
10.1016/j.kint.2016.06.028
ISSN1523-1755
AutoresMatthew B. Rivara, Scott V. Adams, Sooraj Kuttykrishnan, Kamyar Kalantar‐Zadeh, Onyebuchi A. Arah, Alfred K. Cheung, Ronit Katz, Miklos Z. Molnar, Vanessa Ravel, Melissa Soohoo, Elani Streja, Jonathan Himmelfarb, Rajnish Mehrotra,
Tópico(s)Health Systems, Economic Evaluations, Quality of Life
ResumoExtended-hours hemodialysis offers substantially longer treatment time compared to conventional hemodialysis schedules and is associated with improved fluid and electrolyte control and favorable cardiac remodeling. However, whether extended-hours hemodialysis improves survival remains unclear. Therefore, we determined the association between extended-hours compared to conventional hemodialysis and the risk of all-cause mortality in a nationally representative cohort of patients initiating maintenance dialysis in the United States from 2007 to 2011. Survival analyses using causal inference modeling with marginal structural models were performed to compare mortality risk among 1206 individuals undergoing thrice weekly extended-hours hemodialysis or 111,707 patients receiving conventional hemodialysis treatments. The average treatment time per session for extended-hours hemodialysis was 399 minutes compared to 211 minutes for conventional therapy. The crude mortality rate with extended-hours hemodialysis was 6.4 deaths per 100 patient-years compared with 14.7 deaths per 100 patient-years for conventional hemodialysis. In the primary analysis, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk of death compared to those who were treated with a conventional regimen (95% confidence interval: 7% to 51%). Additional analyses accounting for analytical assumptions regarding exposure and outcome, facility-level confounders, and prior modality history were similar. Thus, in this large nationally representative cohort, treatment with extended-hours hemodialysis was associated with a lower risk for mortality compared to treatment with conventional in-center therapy. Adequately powered randomized clinical trials comparing extended-hours to conventional hemodialysis are required to confirm these findings. Extended-hours hemodialysis offers substantially longer treatment time compared to conventional hemodialysis schedules and is associated with improved fluid and electrolyte control and favorable cardiac remodeling. However, whether extended-hours hemodialysis improves survival remains unclear. Therefore, we determined the association between extended-hours compared to conventional hemodialysis and the risk of all-cause mortality in a nationally representative cohort of patients initiating maintenance dialysis in the United States from 2007 to 2011. Survival analyses using causal inference modeling with marginal structural models were performed to compare mortality risk among 1206 individuals undergoing thrice weekly extended-hours hemodialysis or 111,707 patients receiving conventional hemodialysis treatments. The average treatment time per session for extended-hours hemodialysis was 399 minutes compared to 211 minutes for conventional therapy. The crude mortality rate with extended-hours hemodialysis was 6.4 deaths per 100 patient-years compared with 14.7 deaths per 100 patient-years for conventional hemodialysis. In the primary analysis, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk of death compared to those who were treated with a conventional regimen (95% confidence interval: 7% to 51%). Additional analyses accounting for analytical assumptions regarding exposure and outcome, facility-level confounders, and prior modality history were similar. Thus, in this large nationally representative cohort, treatment with extended-hours hemodialysis was associated with a lower risk for mortality compared to treatment with conventional in-center therapy. Adequately powered randomized clinical trials comparing extended-hours to conventional hemodialysis are required to confirm these findings. Although the past decade has witnessed a modest improvement in survival for patients undergoing maintenance dialysis in the United States, mortality continues to be unacceptably high, approaching 20% per year.1United States Renal Data System. 2014 USRDS annual data report. An overview of the epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; 2014.Google Scholar While early observational studies suggested that a higher delivered dose of dialysis may be associated with improved clinical outcomes, a benefit of increasing the dialysis dose above currently accepted standards has not been confirmed by randomized, controlled clinical trial results.2Hakim R.M. Breyer J. Ismail N. et al.Effects of dose of dialysis on morbidity and mortality.Am J Kidney Dis. 1994; 23: 661-669Abstract Full Text PDF PubMed Scopus (385) Google Scholar, 3Miller J.E. Kovesdy C.P. Nissenson A.R. et al.Association of hemodialysis treatment time and dose with mortality and the role of race and sex.Am J Kidney Dis. 2010; 55: 100-112Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 4Eknoyan G. Beck G.J. Cheung A.K. et al.Effect of dialysis dose and membrane flux in maintenance hemodialysis.N Engl J Med. 2002; 347: 2010-2019Crossref PubMed Scopus (1576) Google Scholar This has prompted a search for other modifiable dialysis parameters, including dialysis modality and treatment time, in order to improve long-term clinical outcomes. Consistent with this emphasis, the Institute of Medicine in the United States has identified comparative effectiveness of dialysis therapies as the only kidney disease-related topic among the top 100 national priorities for comparative effectiveness research.5IOM (Institute of Medicine)Initial National Priorities for Comparative Effectiveness Research. The National Academies Press, Washington, DC2009Google Scholar Numerous observational studies over the past 2 decades have demonstrated that shorter treatment times with conventional hemodialysis are associated with higher mortality.6Saran R. Bragg-Gresham J.L. Levin N.W. et al.Longer treatment time and slower ultrafiltration in hemodialysis: Associations with reduced mortality in the DOPPS.Kidney Int. 2006; 69: 1222-1228Abstract Full Text Full Text PDF PubMed Scopus (434) Google Scholar, 7Tentori F. Zhang J. Li Y. et al.Longer dialysis session length is associated with better intermediate outcomes and survival among patients on in-center three times per week hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Nephrol Dial Transplant. 2012; 27: 4180-4188Crossref PubMed Scopus (137) Google Scholar, 8Brunelli S.M. Chertow G.M. Ankers E.D. et al.Shorter dialysis times are associated with higher mortality among incident hemodialysis patients.Kidney Int. 2010; 77: 630-636Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 9Marshall M.R. Byrne B.G. Kerr P.G. et al.Associations of hemodialysis dose and session length with mortality risk in Australian and New Zealand patients.Kidney Int. 2006; 69: 1229-1236Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 10Flythe J.E. Curhan G.C. Brunelli S.M. Shorter length dialysis sessions are associated with increased mortality, independent of body weight.Kidney Int. 2013; 83: 104-113Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar Recently, an increasing number of patients are being treated with extended-hours hemodialysis consisting of substantially longer treatment times, which has been associated in observational studies with lower hospitalization rates and improvements in metabolic parameters, left ventricular mass, and hypertension.11Chan C.T. Floras J.S. Miller J.A. et al.Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis.Kidney Int. 2002; 61: 2235-2239Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar, 12Ok E. Duman S. Asci G. et al.Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis A prospective, case-controlled study.Nephrol Dial Transplant. 2011; 26: 1287-1296Crossref PubMed Scopus (121) Google Scholar, 13Bergman A. Fenton S.S.A. Richardson R.M.A. et al.Reduction in cardiovascular related hospitalization with nocturnal home hemodialysis.Clin Nephrol. 2008; 69: 33-39Crossref PubMed Scopus (42) Google Scholar, 14Powell J.R. Oluwaseun O. Woo Y.M. et al.Ten Years Experience of In-Center Thrice Weekly Long Overnight Hemodialysis.Clin J Am Soc Nephrol. 2009; 4: 1097-1101Crossref PubMed Scopus (39) Google Scholar However, there are limited data on the association of extended-hours hemodialysis with patient survival, as prior studies have been small or single-center investigations, or have not addressed the multiple time-varying and facility-level factors that can cause confounding.15Johansen K.L. Zhang R. Huang Y. et al.Survival and hospitalization among patients using nocturnal and short daily compared to conventional hemodialysis: a USRDS study.Kidney Int. 2009; 76: 984-990Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar, 16Lacson E. Wang W. Lester K. et al.Outcomes Associated with In-Center Nocturnal Hemodialysis from a Large Multicenter Program.Clin J Am Soc Nephrol. 2010; 5: 220-226Crossref PubMed Scopus (64) Google Scholar, 17Lacson E. Xu J. Suri R.S. et al.Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis.J Am Soc Nephrol. 2012; 23: 687-695Crossref PubMed Scopus (120) Google Scholar, 18Nesrallah G.E. Lindsay R.M. Cuerden M.S. et al.Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis.J Am Soc Nephrol. 2012; 23: 696-705Crossref PubMed Scopus (154) Google Scholar, 19Kuttykrishnan S. Kalantar-Zadeh K. Arah O.A. et al.Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research.Nephrol Dial Transplant. 2015; 30: 1208-1217Crossref PubMed Scopus (43) Google Scholar Randomized, controlled trials remain the gold standard for comparative effectiveness research. However, trials that have sought to randomly assign patients to 1 of 2 different dialysis modalities have encountered substantial challenges in enrolling the target number of patients.20Korevaar J.C. Feith G. Dekker F.W. et al.Effect of starting with hemodialysis compared with peritoneal dialysis in patients new on dialysis treatment: A randomized controlled trial.Kidney Int. 2003; 64: 2222-2228Abstract Full Text Full Text PDF PubMed Scopus (323) Google Scholar, 21Rocco M.V. Lockridge R.S. Beck G.J. et al.The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.Kidney Int. 2011; 80: 1080-1091Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar, 22Sergeyeva O. Gorodetskaya I. Ramos R. et al.Challenges to enrollment and randomization of the Frequent Hemodialysis Network (FHN) Daily Trial.J Nephrol. 2012; 25: 302-309Crossref PubMed Scopus (20) Google Scholar These challenges suggest that most patients are not willing to leave the selection of dialysis modality to random assignment if the therapies have substantial and widely differing effects on lifestyle, schedule, and weekly commitment to dialysis-related treatment.22Sergeyeva O. Gorodetskaya I. Ramos R. et al.Challenges to enrollment and randomization of the Frequent Hemodialysis Network (FHN) Daily Trial.J Nephrol. 2012; 25: 302-309Crossref PubMed Scopus (20) Google Scholar Additionally, no contemporary randomized, controlled trial has sought to test the effect of extended hemodialysis treatment time independent of increased treatment frequency. Observational studies using contemporary causal inference modeling such as marginal structural models utilize robust statistical tools that address time-varying exposures and confounding, and thus represent an important alternative method for investigating the comparative effectiveness of dialysis modalities.23Robins J.M. Hernán M.A. Brumback B. Marginal structural models and causal inference in epidemiology.Epidemiology. 2000; 11: 550-560Crossref PubMed Scopus (3361) Google Scholar In this study, we used marginal structural modeling to address the hypothesis that extended-hours hemodialysis is associated with lower risk for all-cause death compared to conventional hemodialysis. The study sample comprised 136,207 individuals with end-stage renal disease who initiated maintenance dialysis from 2007 to 2011 treated in dialysis facilities operated by a large US dialysis provider. Compared to individuals treated exclusively with conventional hemodialysis (n = 111,707), patients categorized as treated with extended-hours hemodialysis for 1 or more 91-day periods (n = 1206) were younger and more likely to be male, be black, have diabetes or comorbid cardiovascular disease, have primary insurance other than Medicare or Medicaid, and live in the western region of the United States (Table 1). Other patients, who were never treated with extended-hours hemodialysis and were treated with at least 1 modality other than conventional hemodialysis, differed from both extended-hours and exclusively conventional hemodialysis patients (Table 1). However, in the first 91-day period of dialysis, laboratory and treatment parameters were similar among patients ever treated with extended-hours hemodialysis, patients exclusively treated with conventional hemodialysis, and other patients (Table 1).Table 1Patient characteristics at the start of the first 91-day dialysis treatment period after initiation of dialysis, by modality, and total proportion of variables with missing informationEver treated with extended-hours hemodialysis (N = 1206)Exclusively treated with conventional hemodialysis (N = 111,707)Others (N = 23,294)% MissingAge, years0 18-24312 25-44281118 45-59422730 60-74243633 ≥7532416Race, %0 Asian334 Black373121 White474758 Hispanic101513 Other343Male, %7057560Primary health insurance,%0 Medicare355346 Medicaid775 Other insurance584048Geographic location0 Northeast, %91312 Midwest, %301819 West, %402541 South, %214428Year of incidence0 2007252020 2008242021 2009242122 2010182122 201191815Coexisting illnesses, %0 Atherosclerotic heart disease211418 Congestive heart failure553730 Diabetes685863 Other cardiovascular191516Access Type, %aAmong patients ever treated with extended hours hemodialysis, 67% were treated with conventional hemodialysis in the first 91-day period. Values for the period prior to extended-hours hemodialysis are available in Supplementary Table S1.6.5 Arteriovenous fistula or graft242011 Central venous catheter738046 Peritoneal dialysis catheter3042Treatment parametersaAmong patients ever treated with extended hours hemodialysis, 67% were treated with conventional hemodialysis in the first 91-day period. Values for the period prior to extended-hours hemodialysis are available in Supplementary Table S1. Body mass index32.5 ± 9.528.2 ± 7.428.3 ± 7.28.7 Pre-dialysis systolic blood pressure, mm Hg152 ± 18147 ± 19148 ± 195.9 Weekday inter-dialytic weight gain, %2.2 [1.5, 3.0]2.3 [1.5, 3.2]0.02 [0.013, 0.029]9.3 Weekend inter-dialytic weight gain, %2.8 [2.0, 4.1]3.1 [2.1, 4.2]0.027 [0.017, 0.038]8.9Laboratory variables Serum albumin, g/dl3.6 ± 0.53.5 ± 0.53.6 ± 0.51.6 Alkaline phosphatase, u/l∗P > 0.05 for the difference between extended-hours and conventional hemodialysis groups using ANOVA, Kruskal-Wallis test, or chi-square test. P < 0.05 for all other comparisons.87 [69, 111]87 [69, 115]82 [65, 106]1.8 Serum calcium, mg/dl9.1 ± 0.69.1±0.69.1 ± 0.61.5 Serum ferritin, ng/ml234 [138, 373]282 [164, 484]237 [133, 413]2.8 Hemoglobin, g/dl∗P > 0.05 for the difference between extended-hours and conventional hemodialysis groups using ANOVA, Kruskal-Wallis test, or chi-square test. P < 0.05 for all other comparisons.11.1 ± 1.211.1 ± 1.211.3 ± 1.21.3 Serum iron saturation, %21 [17,25]22 [17, 27]23 [18, 29]2.1 Parathyroid hormone, pg/ml378 [240, 569]314 [197, 486]294 [183, 470]2.0 Serum phosphorous, mg/dl5.3 ± 1.24.9 ± 1.24.9 ± 1.11.5 spKt/V urea1.4 [1.2, 1.8]1.6 [1.4, 1.8]1.4 [1.2, 1.7]8.2Parenteral medications Cumulative iron, mg/mo1062 [525, 1600]1000 [400, 1400]400 [0, 1050]0 Erythropoietin dose, units/wk26,950 [16,500; 36,300]24,900 [13,200; 33,000]17,600 [9000; 29,700]0Summary statistics are mean ± SD, median and interquartile range, or proportions (%).∗ P > 0.05 for the difference between extended-hours and conventional hemodialysis groups using ANOVA, Kruskal-Wallis test, or chi-square test. P < 0.05 for all other comparisons.a Among patients ever treated with extended hours hemodialysis, 67% were treated with conventional hemodialysis in the first 91-day period. Values for the period prior to extended-hours hemodialysis are available in Supplementary Table S1. Open table in a new tab Summary statistics are mean ± SD, median and interquartile range, or proportions (%). Patients who initiated extended-hours hemodialysis following 1 or more 91-day periods of conventional hemodialysis had higher serum alkaline phosphatase, ferritin, parathyroid hormone, and spKt/V, and lower serum phosphorous, cumulative iron dose (prescribed over each 91-day period), and median erythropoietin dose during treatment with extended-hours hemodialysis compared to values during treatment with conventional hemodialysis prior to transfer (Supplementary Table S1). The average delivered treatment time per session with extended-hours hemodialysis was 399 ± 64 minutes, compared to 211 ± 27 minutes with conventional hemodialysis (intra-patient coefficient of variation 10.8% and 6.8%, respectively) (Figure 1). Treatment frequency was similar among patients treated with extended-hours hemodialysis (2.8 treatments per week, interquartile range [IQR 2.4, 2.9]) and conventional hemodialysis (2.9 treatments per week, [IQR 2.7, 2.9]). Among extended-hours hemodialysis patients, extended-hours hemodialysis was the initial dialysis modality for 353 patients (29.3%); 823 patients (68.2%) started dialysis with conventional hemodialysis, 37 (3%) started with peritoneal dialysis, and 6 (0.5%) initiated with home hemodialysis or in-center hemodialysis less than 3 times per week. Overall, median time from initiation of dialysis to start of treatment with extended-hours hemodialysis was 6.7 months (IQR 1.0, 19.2). The median duration between initiation of hemodialysis and transfer to another modality, censoring, or death was 7.6 months (IQR 2.3, 17.6) for conventional hemodialysis and 7.2 months (IQR 3.4, 15.1) for extended-hours hemodialysis. Of patients treated with extended-hours hemodialysis, 535 (44%) transferred to another dialysis modality for 1 or more 91-day periods. Of these patients, none died and 78 were censored (66 due to end of follow-up) within 91 days of transfer from extended-hours hemodialysis. Of patients treated with conventional hemodialysis, 10% later transferred to another modality. In total, 82 patients died during a 91-day period in which they were receiving extended-hours hemodialysis, compared to 29,778 deaths during periods of conventional hemodialysis. Crude mortality rates were 6.4 and 14.7 deaths per 100 patient-years for extended-hours and conventional hemodialysis, respectively (Table 2). Adjusted for treatment history and time-varying laboratory and treatment parameters using marginal structural models, as well as for case-mix factors, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk for death compared to those treated with conventional hemodialysis (95% confidence interval [CI] 7% to 51% lower) (Table 2).Table 2Risks for all-cause mortality comparing extended-hours hemodialysis to conventional hemodialysis, by time period for dialysis modality death attributionDeath attributionHemodialysis modalityNumber of deathsPatient-years of follow-upMortality rateaMortality rate per 100 person-yearsHazard ratiobHazard ratio from marginal structural Cox model comparing extended-hours hemodialysis to conventional hemodialysis, reference group: conventional hemodialysis, adjusted for age, sex, race, year of incidence, insurance, congestive heart failure, diabetes, arteriosclerotic heart disease, and other cardiovascular comorbidities. (95% CI)Current dialysis modality at time of deathcDeath attributed to the dialysis modality for the 91-day period in which the death occurred.Extended-hours8212796.40.67 (0.49, 0.93)Conventional29,796203,04614.7Dialysis modality of 91-day period prior to deathdDeath attributed to the dialysis modality of the 91-day period prior to the 91-day period in which death occurred.Extended-hours821,2796.40.68 (0.49, 0.93)Conventional29,692203,02814.6Extended-hours, for all events after extended-hours initiationExtended-hours12618656.80.62 (0.47, 0.81)Conventional29,761202,58214.7a Mortality rate per 100 person-yearsb Hazard ratio from marginal structural Cox model comparing extended-hours hemodialysis to conventional hemodialysis, reference group: conventional hemodialysis, adjusted for age, sex, race, year of incidence, insurance, congestive heart failure, diabetes, arteriosclerotic heart disease, and other cardiovascular comorbidities.c Death attributed to the dialysis modality for the 91-day period in which the death occurred.d Death attributed to the dialysis modality of the 91-day period prior to the 91-day period in which death occurred. Open table in a new tab Attributing deaths to the dialysis modality 90 days prior to death did not meaningfully change the risk estimate (Table 2). An extreme approach—attributing all deaths following initiation of extended-hours hemodialysis to extended-hours hemodialysis, regardless of the actual modality at the time of death—increased the number of deaths attributed to extended-hours hemodialysis to 126, but the risk ratio between extended-hours and conventional hemodialysis did not change substantially (HR 0.62 [0.47 to 0.81]. (Table 2). Starting follow-up from the 91st day after start of dialysis, further adjustment for vascular access type, or restricting the cohort to patients for whom extended-hours dialysis treatment was most likely to be available did not meaningfully change hazard ratio estimates (Table 3). Additionally, results of analyses among a restricted cohort that excluded patients who never initiated extended-hours hemodialysis, but to whom extended-hours hemodialysis was available, were similar (Table 3). Results from a matched analysis in which each patient ever treated with extended-hour hemodialysis was matched with up to 20 other patients who had the same dialysis modality treatment history prior to initiation of extended-hours hemodialysis were not substantially different (Table 3). Finally, in interaction analyses, no evidence of effect modification by age, sex, or race was found (P > 0.2 for each).Table 3Results of analyses with alternative assumptions: risks for all-cause mortality comparing extended-hours hemodialysis to conventional hemodialysisAnalysisExtended-hours hemodialysisConventional hemodialysisHazard ratioaHazard ratio for all-cause mortality comparing extended-hours with conventional hemodialysis, adjusted for age, sex, race, year of incidence, insurance, congestive heart failure, diabetes, arteriosclerotic heart disease, and other cardiovascular comorbidities.95% CIDeathsPatient-yearsDeathsPatient-yearsBeginning analysis 91 days after dialysis initiation82120229,654176,5080.67(0.47, 0.94)Including only patients with access to extended-hours hemodialysisbA patient was identified as having access to extend-hours dialysis if (i) she or he was treated with extended-hours dialysis at any time, or (ii) she or he was treated at a facility that had treated another patient who was treated with extended hours dialysis at any time (at any facility).82127911,64376,9800.68(0.50, 0.93)Excluding patients who never initiated extended-hours hemodialysis, but to whom it was available82127918,656122,3340.67(0.49, 0.91)Additional adjustment for vascular access82127929,796203, 0460.69(0.50, 0.95)Matched cohortcExtended-hours hemodialysis patients were matched with up to 20 other patients with the same modality for each 91-day period prior to initiating extended-hours hemodialysis and the same age category, sex, race, year of dialysis incidence, underlying renal disease, Charlson comorbidity index, and geographic region. All patients were drawn from those to whom extended-hours hemodialysis was available.731470204117,7170.58(0.43, 0.79)a Hazard ratio for all-cause mortality comparing extended-hours with conventional hemodialysis, adjusted for age, sex, race, year of incidence, insurance, congestive heart failure, diabetes, arteriosclerotic heart disease, and other cardiovascular comorbidities.b A patient was identified as having access to extend-hours dialysis if (i) she or he was treated with extended-hours dialysis at any time, or (ii) she or he was treated at a facility that had treated another patient who was treated with extended hours dialysis at any time (at any facility).c Extended-hours hemodialysis patients were matched with up to 20 other patients with the same modality for each 91-day period prior to initiating extended-hours hemodialysis and the same age category, sex, race, year of dialysis incidence, underlying renal disease, Charlson comorbidity index, and geographic region. All patients were drawn from those to whom extended-hours hemodialysis was available. Open table in a new tab Using contemporary causal inference methods in this large study of incident dialysis patients, we found that treatment with thrice-weekly extended-hours hemodialysis was associated with 34% lower risk for death compared with conventional hemodialysis. Our results were robust, with consistent treatment effect estimates in multiple sensitivity analyses accounting for temporal assumptions regarding exposure and outcome, facility-level confounders related to the availability of extended-hours hemodialysis to patients, and prior modality history. To our knowledge, this is the largest study of extended-hours hemodialysis reported. The past decade has seen a resurgent interest in exploring the benefit of more frequent and/or longer dialysis treatments. Culleton et al.24Culleton B.F. Walsh M. Klarenbach S.W. et al.Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: A randomized controlled trial.JAMA. 2007; 298: 1291-1299Crossref PubMed Scopus (583) Google Scholar randomly assigned 52 patients in Canada to thrice-weekly in-center or home hemodialysis versus 6 times–weekly nocturnal hemodialysis, and found that the latter therapy resulted in a decrease in left ventricular mass and systolic blood pressure and a reduction in serum phosphorus and parathyroid hormone levels. The Frequent Hemodialysis Network (FHN) nocturnal trial compared conventional thrice-weekly hemodialysis performed at home with frequent home nocturnal hemodialysis performed 6 times weekly for ≥6 hours per session, and showed that frequent nocturnal therapy resulted in lower blood pressure and reductions in serum phosphorus.21Rocco M.V. Lockridge R.S. Beck G.J. et al.The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.Kidney Int. 2011; 80: 1080-1091Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Surprisingly, long-term follow-up of patients enrolled in the FHN nocturnal trial found an increased risk for death in the nocturnal dialysis group, although caution should be exercised in interpretation of these results given an unexpectedly low mortality rate observed in the conventional dialysis group and high rates of dialysis modality switches in this study.25Rocco M.V. Daugirdas J.T. Greene T. et al.Long-term effects of frequent nocturnal hemodialysis on mortality: the Frequent Hemodialysis Network (FHN) nocturnal trial.Am J Kidney Dis. 2015; 66: 459-468Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar Of note, these 2 trials assessed the impact of increasing both hemodialysis treatment time and treatment frequency together, and thus did not allow for assessment of the independent effect of changing treatment time. In the recently reported A Clinical Trial of IntensiVE Dialysis (ACTIVE Dialysis) trial, extending hemodialysis hours to a target of ≥24 hours weekly compared to standard dialysis hours (12–15 hours weekly) resulted in reductions in serum phosphorus and blood pressure medication requirements.26Jardine M.J. Zuo L. Gray N.A. et al.impact of extended weekly hemodialysis hours on quality of life and clinical outcomes: the ACTIVE Dialysis multinational trial.J Am Soc Nephrol. 2014; 25: B2Google Scholar However, similar to the aforementioned FHN and Canadian trials of nocturnal hemodialysis, the intervention in ACTIVE Dialysis was not designed to assess the independent impact of extending hemodialysis treatment times separate from changes in treatment frequency.27Jardine M.J. Zuo L.I. Gray N.A. et al.Design and participant baseline characteristics of "A Clinical Trial of IntensiVE Dialysis": the ACTIVE Dialysis Study.Nephrol Carlton Vic. 2015; 20: 257-265Crossref PubMed Scopus (19) Google Scholar In contrast, the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial is an ongoing pragmatic randomized clinical trial designed to test the hypothesis that thrice-weekly hemodialysis with session durations of at least 4.25 hours improves mortality, hospitalization, and health-related quality of life compared to usual care, consisting of treatments with a mean duration of 3.5 hours.28National Institute of Diabetes and Digestive and Kidney Diseases, University of Pennsylvania. A Cluster-randomized, Pragmatic Trial of Hemodialysis Session Duration (TiME). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000.Google Scholar However, given this relatively small increase in tre
Referência(s)