Novel techniques and innovation in blood purification: a clinical update from Kidney Disease: Improving Global Outcomes
2013; Elsevier BV; Volume: 83; Issue: 3 Linguagem: Inglês
10.1038/ki.2012.450
ISSN1523-1755
AutoresChristopher T. Chan, Adrian Covic, Jonathan C. Craig, Andrew Davenport, Bertram L. Kasiske, Martin K. Kuhlmann, Nathan W. Levin, Philip Kam‐Tao Li, Francesco Locatelli, Michael V. Rocco, David C. Wheeler,
Tópico(s)Chronic Kidney Disease and Diabetes
ResumoMortality in patients with end-stage renal disease (ESRD) remains unacceptably high. Emerging techniques and advances in dialysis technology have the potential to improve clinical outcomes in the ESRD population. This report summarizes the deliberations and recommendations of a conference sponsored by Kidney Disease: Improving Global Outcomes to address the following questions: (1) what is the appropriate frequency and duration of hemodialysis; (2) how should we optimize water quality and dialysate composition; and (3) what technical innovations in blood purification and bioengineering can result in better clinical outcomes? The conference report will augment our current understanding of clinical practice in blood purification and will pose several high-priority research questions. Mortality in patients with end-stage renal disease (ESRD) remains unacceptably high. Emerging techniques and advances in dialysis technology have the potential to improve clinical outcomes in the ESRD population. This report summarizes the deliberations and recommendations of a conference sponsored by Kidney Disease: Improving Global Outcomes to address the following questions: (1) what is the appropriate frequency and duration of hemodialysis; (2) how should we optimize water quality and dialysate composition; and (3) what technical innovations in blood purification and bioengineering can result in better clinical outcomes? The conference report will augment our current understanding of clinical practice in blood purification and will pose several high-priority research questions. Kidney Disease: Improving Global Outcomes convened a Controversies Conference in Paris from 14 to 15 October 2011, titled 'Novel techniques and innovation in blood purification: How can we improve clinical outcomes in hemodialysis?' The conference, attended by 50 international experts, was designed to establish consensus and directions for optimal modes of blood purification. The plenary session presentations were followed by breakout group discussions to address three specific topic areas: (1) dialysis technique—frequency and duration; (2) dialysate composition and toxins; and (3) technical advances in dialysis. The breakout group deliberations were reported to the entire group, and a consensus-building process led to the clinical practice and research recommendations from the conference attendees, which are the substance of this report. The report was reviewed by all breakout group leaders, cochairs, and representatives of the Kidney Disease: Improving Global Outcomes Board of Directors. The conference agenda, selected presentations, and abstracts of the meeting are available on the Kidney Disease: Improving Global Outcomes website (http://www.kdigo.org/meetings_events/novel_tech.php). The recent interest in novel techniques and innovation in blood purification was born out of the impasse in an effort to improve survival and quality of life of patients with end-stage renal disease (ESRD). Although there have been medical and technical advances, mortality rate of patients with ESRD remains unacceptably high at about 10–20% per year. To date, most medical interventions have failed to change the survival of ESRD patients.1Besarab A. Bolton W.K. Browne J.K. et al.The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.N Engl J Med. 1998; 339: 584-590Crossref PubMed Scopus (1398) Google Scholar,2Wanner C. Krane V. Marz W. et al.Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.N Engl J Med. 2005; 353: 238-248Crossref PubMed Scopus (1483) Google Scholar It was suggested that the high mortality rate in ESRD was related to poor clearance of uremic toxins within the three-times-a-week paradigm. This hypothesis was tested in the Hemodialysis Study, a randomized controlled study that did not demonstrate a positive effect on patient survival when dialysis dose was increased from a pretreatment Kt/V of 1.32 to 1.71.3Eknoyan 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 (1085) Google Scholar Of equal importance is that the Hemodialysis Study did not demonstrate any overall benefit related to the use of high-flux versus low-flux dialyzers.3Eknoyan 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 (1085) Google Scholar Recently, another randomized trial in Europe, the Membrane Permeability Outcome Study, was unable to show improved survival in all patients treated with high-flux membranes.4Locatelli F. Martin-Malo A. Hannedouche T. et al.Effect of membrane permeability on survival of hemodialysis patients.J Am Soc Nephrol. 2009; 20: 645-654Crossref PubMed Scopus (199) Google Scholar Although the provision of more intensive conventional hemodialysis has not reduced mortality, more frequent hemodialysis has demonstrated improvements in several clinical surrogate outcomes. Indeed, the Frequent Hemodialysis Network (FHN) Daily Dialysis and the Alberta Kidney Disease Network (AKDN) Trials have reported regression of left ventricular (LV) hypertrophy, improved blood pressure control, and better quality of life.5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar Other observational studies have suggested better survival (compared with conventional hemodialysis) with more frequent hemodialysis.8Pauly R.P. Gill J.S. Rose C.L. et al.Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients.Nephrol Dial Transplant. 2009; 24: 2915-2919Crossref PubMed Scopus (89) Google Scholar,9Johansen 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 (89) Google Scholar At the same time, use of convective techniques, such as hemodiafiltration (HDF), has increased and is now common in Europe and in other parts of the world. Survival advantage,10Canaud B. Bragg-Gresham J.L. Marshall M.R. et al.Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS.Kidney Int. 2006; 69: 2087-2093Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar hemodynamic stability,11Locatelli F. Altieri P. Andrulli S. et al.Hemofiltration and hemodiafiltration reduce intradialytic hypotension in ESRD.J Am Soc Nephrol. 2010; 21: 1798-1807Crossref PubMed Scopus (0) Google Scholar and enhanced clearance of small and middle molecules12Locatelli F. Manzoni C. Vigano S. et al.Hemodiafiltration - state of the art.Contrib Nephrol. 2010; 168: 5-18Crossref PubMed Scopus (5) Google Scholar have been reported with the use of HDF, but reports of larger controlled trials in Turkey and the Netherlands have not shown an overall survival advantage.13Grooteman M.P. van den Dorpel M.A. Bots M.L. et al.Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes.J Am Soc Nephrol. 2012; 23: 1087-1096Crossref PubMed Scopus (135) Google Scholar,14Ok E. Asci G. Toz H. et al.Comparison of Postdilution On-line Hemodiafiltration and Hemodialysis (Turkish HDF Study). ERA-EDTA Congress Prague, Czech Republic2011Google Scholar With the increase in the worldwide chronic dialysis population and the growth of renal replacement therapy programs in large countries such as China and India, it has become evident that advances in technology and process are required to facilitate the widespread clinical application of renal replacement therapy. At present, most dialysis machines are not engineered to be used easily by patients. Improved flexibility of a dialysis platform for users with different levels of training and skills will likely transform the clinical landscape of ESRD care. Other novel technical advances in blood purification include application of nanotechnology,15Rastogi A. Nissenson A.R. Technological advances in renal replacement therapy: five years and beyond.Clin J Am Soc Nephrol. 2009; 4: S132-S136Crossref PubMed Scopus (13) Google Scholar,16Fissell W.H. Fleischman A.J. Humes H.D. et al.Development of continuous implantable renal replacement: past and future.Transl Res. 2007; 150: 327-336Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar the use of sorbents to remove uremic toxins and regenerate water for dialysis,17Ash S.R. Sorbents in treatment of uremia: a short history and a great future.Semin Dial. 2009; 22: 615-622Crossref PubMed Scopus (14) Google Scholar 'wearable kidneys,'18Gura V. Macy A.S. Beizai M. et al.Technical breakthroughs in the wearable artificial kidney (WAK).Clin J Am Soc Nephrol. 2009; 4: 1441-1448Crossref PubMed Scopus (31) Google Scholar,19Davenport A. Ronco C. Gura V. Portable and wearable dialysis: where are we now?.Hemodial Int. 2010; 14: S22-S26Crossref PubMed Google Scholar and the incorporation of renal cells as part of a bioartificial kidney.15Rastogi A. Nissenson A.R. Technological advances in renal replacement therapy: five years and beyond.Clin J Am Soc Nephrol. 2009; 4: S132-S136Crossref PubMed Scopus (13) Google Scholar, 20Song J.H. Humes H.D. Renal cell therapy and beyond.Semin Dial. 2009; 22: 603-609Crossref PubMed Scopus (17) Google Scholar, 21Nissenson A.R. Ronco C. Pergamit G. et al.The human nephron filter: toward a continuously functioning, implantable artificial nephron system.Blood Purif. 2005; 23: 269-274Crossref PubMed Scopus (38) Google Scholar The clinical applications of novel biomaterials22Canaud B. Formaldehyde-fixed arterial allograft as a novel vascular access alternative in end-stage renal disease patients.Kidney Int. 2007; 72: 1179-1181Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar and therapeutic use of endothelial23Conte M.S. Nugent H.M. Gaccione P. et al.Multicenter phase I/II trial of the safety of allogeneic endothelial cell implants after the creation of arteriovenous access for hemodialysis use: the V-HEALTH study.J Vasc Surg. 2009; 50: 1359-1368Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar or endothelial progenitor cells24Roy-Chaudhury P. Endothelial progenitor cells, neointimal hyperplasia, and hemodialysis vascular access dysfunction: novel therapies for a recalcitrant clinical problem.Circulation. 2005; 112: 3-5Crossref PubMed Scopus (22) Google Scholar may provide much needed innovation in vascular access devices (Figure 1). More frequent dialysis than the standard three-times-a-week has been performed since the 1960s;25Baillod R. Comty C.M. Shaldon S. Over-night haemodialysis in the home.Proc Eur Dial Transplant Assoc. 1966; 2: 99-104Google Scholar, 26Blagg C.R. Hickman R.O. Eschbach J.W. et al.Home hemodialysis: six years' experience.N Engl J Med. 1970; 283: 1126-1131Crossref PubMed Google Scholar, 27Bonomini V. Mioli V. Albertazzi A. et al.Daily-dialysis programme: indications and results. Proceedings of the European Dialysis and Transplant Association.Eur Dialysis Transplant Assoc. 1972; 9: 44-52PubMed Google Scholar, 28De Palma J.R. Pea M.M. A new automatic coil dialyzer system for 'daily' dialysis.Proc Eur Dial Transplant Assoc. 1969; 6: 26-34Google Scholar, 29Eschbach J.W. Barnett B.M. Cole J.J. et al.Hemodialysis in the home. A new approach to the treatment of chronic uremia.Ann Intern Med. 1967; 67: 1149-1162Crossref PubMed Google Scholar, 30Eschbach J.W. Wilson W.E. Peoples R.W. et al.Unattended overnight home hemodialysis.Trans Am Soc Artif Intern Organs. 1966; 12: 346-356PubMed Google Scholar however, there is no uniform nomenclature to describe the different types of more frequent hemodialysis. Our group proposes that all hemodialysis prescriptions should be described by indicating both duration of the individual dialysis session and the frequency per week (Table 1).Table 1Descriptive nomenclature for hemodialysis frequency and durationConventional hemodialysis3–5h per session, three times per weekShort daily hemodialysisLess than 3h per session, six times per weekStandard daily hemodialysis3–5h per session, six times per weekLong daily hemodialysisMore than 5h per session, six times per week Open table in a new tab Other frequencies can also be derived from this nomenclature, such as conventional indicates three times per week, and the words short, standard, and long denote the length of an individual dialysis session. Other increased frequency lengths include every other day and four or five times per week hemodialysis. The location of the dialysis session should be indicated as in-center, self-care (for patient-assisted in-center hemodialysis), home-assisted (for staff-assisted home hemodialysis), and home (for patient provided home hemodialysis). The use of a standard nomenclature for describing the dialysis prescription should assist in comparative studies and in meta-analyses of different, more frequent hemodialysis prescriptions. As early as 1972, Bonomini et al.27Bonomini V. Mioli V. Albertazzi A. et al.Daily-dialysis programme: indications and results. Proceedings of the European Dialysis and Transplant Association.Eur Dialysis Transplant Assoc. 1972; 9: 44-52PubMed Google Scholar noted that changing patients to short daily dialysis (3–4h for 5 days per week) led to a resolution of severe anemia, polyneuropathy, insomnia, pruritus, restless leg syndrome, anorexia, amenorrhea, and impotence. Similar improvements in these and other areas, such as blood pressure control and LV hypertrophy, have been noted by many other investigators since that time in both Europe and North America.31Buoncristiani U. Fifteen years of clinical experience with daily haemodialysis.Nephrol Dial Transplant. 1998; 13: s148-s151Crossref PubMed Scopus (74) Google Scholar, 32Kooistra M.P. Vos J. Koomans H.A. et al.Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life.Nephrol Dial Transplant. 1998; 13: 2853-2860Crossref PubMed Scopus (176) Google Scholar, 33Lindsay R.M. Leitch R. Heidenheim A.P. et al.The London Daily/Nocturnal Hemodialysis Study--study design, morbidity, and mortality results.Am J Kidney Dis. 2003; 42: 5-12Abstract Full Text Full Text PDF PubMed Google Scholar, 34Reynolds J.T. Homel P. Cantey L. et al.A one-year trial of in-center daily hemodialysis with an emphasis on quality of life.Blood Purif. 2004; 22: 320-328Crossref PubMed Scopus (36) Google Scholar Despite the enthusiasm for more frequent dialysis therapies, it was not until the 21st century that randomized trials were performed to assess the potential risks and benefits of more frequent hemodialysis modalities. As late as 2006, a review of daily in-center hemodialysis was based on only 25 published manuscripts since 1989, which included information on five or more patients, followed up for at least 3 months, and were receiving a dialysis prescription of 1.5–3h for 5–7 days per week.35Suri R.S. Nesrallah G.E. Mainra R. et al.Daily hemodialysis: a systematic review.Clin J Am Soc Nephrol. 2006; 1: 33-42Crossref PubMed Scopus (128) Google Scholar A total of 14 cohorts with 268 unique patients were described in these publications, with only 1 randomized trial. There was a benefit of daily in-center hemodialysis in improving the control of hypertension, by either reducing the number of antihypertensive medications required and/or improving systolic and diastolic blood pressures. The findings for both serum albumin levels and quality of life were mixed, with 5 of 10 studies demonstrating an improvement in these parameters. Improvement in phosphate control, as determined by either lower serum phosphate levels or a decrease in the utilization of phosphate binders, was seen in only two of eight studies. Finally, there was no change in the rate of vascular access dysfunction in five of the seven reported studies. Similarly, a review of nocturnal hemodialysis, published in 2005, identified only 10 manuscripts and 4 abstracts that reported on at least 1 of 4 outcomes of interest, had follow-up of at least 4 months, included a comparator group (case–control or pre/post within patient comparison), and provided a dialysis prescription of at least 5 nights per week and 6h per session.36Walsh M. Culleton B. Tonelli M. et al.A systematic review of the effect of nocturnal hemodialysis on blood pressure, left ventricular hypertrophy, anemia, mineral metabolism, and health-related quality of life.Kidney Int. Apr 2005; 67: 1500-1508Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar A total of 4 cohorts with 4–63 patients per cohort were found, with follow-up ranging from 6 weeks to 3.4 years; none of the studies were randomized trials. Daily nocturnal hemodialysis improved the control of hypertension, by both reducing the number of antihypertensive medications required and improving systolic and diastolic blood pressures. This therapy was shown to improve anemia, either by a reduction in erythropoietin dose or by an increase in hemoglobin levels. Improvement in phosphate control, as determined by either serum phosphate levels or a decrease in the utilization of phosphate binders, was seen in one of two studies. Analysis of more recent retrospective data has shown a survival benefit for patients who undergo more frequent home hemodialysis compared with in-center hemodialysis; however, these analyses are confounded by selection bias and lack of information on the socioeconomic and biochemical data adjustment.9Johansen 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 (89) Google Scholar, 37Blagg C.R. Kjellstrand C.M. Ting G.O. et al.Comparison of survival between short-daily hemodialysis and conventional hemodialysis using the standardized mortality ratio.Hemodial Int. 2006; 10: 371-374Crossref PubMed Scopus (48) Google Scholar, 38Kjellstrand C.M. Buoncristiani U. Ting G. et al.Short daily haemodialysis: survival in 415 patients treated for 1006 patient-years.Nephrol Dial Transplant. 2008; 23: 3283-3289Crossref PubMed Scopus (113) Google Scholar, 39Marshall M.R. Hawley C.M. Kerr P.G. et al.Home hemodialysis and mortality risk in Australian and New Zealand populations.Am J Kidney Dis. 2011; 58: 782-793Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Several randomized studies have been performed with more frequent hemodialysis prescriptions, including the FHN studies in both short-daily5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar and long-nocturnal hemodialysis,7Rocco 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 (159) Google Scholar as well as the AKDN Trial of long-nocturnal hemodialysis.6Culleton 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 (336) Google Scholar Benefits of more frequent dialysis in all studies include improved control of hypertension (less antihypertensive medications prescribed and lower systolic and diastolic blood pressures)5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar, 40Kotanko P. Stokes J. Garg A. et al.Temporal evolution of systolic and diastolic blood pressure in the Frequent Hemodialysis Network (FHN) Trials.J Am Soc Nephrol. 2011; 490AGoogle Scholar and hyperphosphatemia (fewer phosphate binders prescribed and lower serum phosphorus levels).5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar, 41Daugirdas J.T. Chertow G.M. Larive B. et al.Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.J Am Soc Nephrol. 2012; 23: 727-738Crossref PubMed Scopus (36) Google Scholar, 42Walsh M. Manns B.J. Klarenbach S. et al.The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized-controlled trial.Hemodial Int. 2010; 14: 174-181Crossref PubMed Scopus (32) Google Scholar In the FHN Daily and AKDN studies, there was a significant decline in LV mass (13.8g (95% confidence intervals, -21.8 to -5.8g) in the FHN Daily study and 15.3g (95% confidence intervals, -29.6 to -1.0g) in the AKDN study).5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 43Chan C.T. Greene T. Chertow G.M. et al.Determinants of left ventricular mass in patients on hemodialysis: Frequent Hemodialysis Network (FHN) Trials.Circ Cardiovasc Imaging. 2012; 5: 251-261Crossref PubMed Scopus (36) Google Scholar In the FHN Nocturnal study, however, there was a decrease in LV mass that was not statistically significant (-10.8g; 95% confidence intervals, -23.7 to +1.8).7Rocco 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 (159) Google Scholar In the FHN Daily Trial, there was an improvement in the self-reported RAND Physical Health Composite, self-reported score in the more frequent hemodialysis (HD) group, but in the FHN Nocturnal study, there was a small nonsignificant increase in this score in both groups, perhaps related to the performance of hemodialysis at home in both groups.5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 7Rocco 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 (159) Google Scholar, 44Hall Y.N. Larive B. Painter P. et al.Effects of six versus three times per week hemodialysis on physical performance, health, and functioning: Frequent Hemodialysis Network (FHN) Randomized Trials.Clin J Am Soc Nephrol. 2012; 7: 782-794Crossref PubMed Scopus (26) Google Scholar In neither group, however, there were improvements noted in objective measures of physical performance.44Hall Y.N. Larive B. Painter P. et al.Effects of six versus three times per week hemodialysis on physical performance, health, and functioning: Frequent Hemodialysis Network (FHN) Randomized Trials.Clin J Am Soc Nephrol. 2012; 7: 782-794Crossref PubMed Scopus (26) Google Scholar Neither of the nocturnal studies showed a benefit in overall quality of life.7Rocco M.V. Lockridge R.S. 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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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar, 46Ornt D. Kliger A. Suri R. et al.The impact of frequent in-center conventional hemodialysis on anemia: the Frequent Hemodialysis Network Trial.J Am Soc Nephrol. 2011; 476AGoogle Scholar depression,5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar, 47Unruh M. Larive B. Chertow G. et al.Effects of six versus three times per week hemodialysis on depressive affect and mental health: Frequent Hemodialysis Network (FHN) Trials.J Am Soc Nephrol. 2011; 255AGoogle Scholar cognitive function,5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar,7Rocco 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 (159) Google Scholar or nutrition (as measured by serum albumin levels).5Chertow G.M. Levin N.W. Beck G.J. et al.In-center hemodialysis six times per week versus three times per week.N Engl J Med. 2010; 363: 2287-2300Crossref PubMed Scopus (411) Google Scholar, 6Culleton 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 (336) Google Scholar, 7Rocco 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 (159) Google Scholar, 48Schorr M. Manns B.J. Culleton B. et al.The effect of nocturnal and conventional hemodialysis on markers of nutritional status: results from a randomized trial.J Ren Nutr. 2011; 21: 271-276Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar There are several caveats to these findings, including their generalizability, as patients in all three studies were significantly younger compared with the average hemodialysis patient, and more predominantly male patient.49Rocco M.V. Larive B. Eggers P.W. et al.Baseline characteristics of participants in the Frequent Hemodialysis Network (FHN) daily and nocturnal trials.Am J Kidney Dis. 2011; 57: 90-100Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar There are also several significant differences between the FHN Nocturnal and AKDN trials. Fi
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