The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration

Abstract

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients’ quality of life, most pronounced with respect to their cognitive function.RegistrationNTR7138 on the International Clinical Trials Registry Platform In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients’ quality of life, most pronounced with respect to their cognitive function. NTR7138 on the International Clinical Trials Registry Platform Lay SummaryPeople with end-stage chronic kidney disease have a life-limiting condition. As the disease progresses further, many of those may require renal replacement therapy. Compared with widely used hemodialysis, hemodiafiltration improves the clearance of specific types of uremic toxins. In the CONVINCE clinical trial, 1360 patients on high-flux hemodialysis were randomly assigned to continue with high-flux hemodialysis or switch to high-volume hemodiafiltration. In this trial, hemodiafiltration prolonged life expectancy compared with hemodialysis. We also investigated which treatment is associated with a better quality of life and collected self-report questionnaires from both groups over the course of the study. By the end of the study, patients treated with hemodiafiltration reported a better quality of life, in particular with respect to their cognitive function, compared with those receiving hemodialysis. People with end-stage chronic kidney disease have a life-limiting condition. As the disease progresses further, many of those may require renal replacement therapy. Compared with widely used hemodialysis, hemodiafiltration improves the clearance of specific types of uremic toxins. In the CONVINCE clinical trial, 1360 patients on high-flux hemodialysis were randomly assigned to continue with high-flux hemodialysis or switch to high-volume hemodiafiltration. In this trial, hemodiafiltration prolonged life expectancy compared with hemodialysis. We also investigated which treatment is associated with a better quality of life and collected self-report questionnaires from both groups over the course of the study. By the end of the study, patients treated with hemodiafiltration reported a better quality of life, in particular with respect to their cognitive function, compared with those receiving hemodialysis. Kidney diseases are highly prevalent and associated with increased mortality.1Jha V. Garcia-Garcia G. Iseki K. et al.Chronic kidney disease: global dimension and perspectives.Lancet. 2013; 382: 260-272Abstract Full Text Full Text PDF PubMed Scopus (3088) Google Scholar The health of patients with kidney failure is affected by specific symptoms, limitations in functional status, and burden of kidney replacement therapy (KRT).2Valderrabano F. Jofre R. Lopez-Gomez J.M. Quality of life in end-stage renal disease patients.Am J Kidney Dis. 2001; 38: 443-464Abstract Full Text Full Text PDF PubMed Google Scholar Next to mortality and morbidity, physical and psychosocial aspects of perceived health, often also described as health-related quality of life (HRQoL), are important outcomes for patients with kidney disease.3Tong A. Manns B. Hemmelgarn B. et al.Establishing core outcome domains in hemodialysis: report of the Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) consensus workshop.Am J Kidney Dis. 2017; 69: 97-107Abstract Full Text Full Text PDF PubMed Google Scholar,4Verberne W.R. Das-Gupta Z. Allegretti A.S. et al.Development of an international standard set of value-based outcome measures for patients with chronic kidney disease: a report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD Working Group.Am J Kidney Dis. 2019; 73: 372-384Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar As enhancing the HRQoL of the patients is a primary objective of KRT,5Gilbert J. Lovibond K. Mooney A. Dudley J. Renal replacement therapy: summary of NICE guidance.BMJ. 2018; 363k4303PubMed Google Scholar a critical inquiry arises as to whether distinct kidney replacement treatment modalities, in particular hemodiafiltration (HDF) versus conventional hemodialysis (HD), differentially affect patient health.6Blankestijn P.J. Fischer K.I. Barth C. et al.Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol.BMJ Open. 2020; 10e033228Crossref PubMed Scopus (46) Google Scholar Several mechanisms have been discussed that might lead to improved health perceptions and reduced treatment burden, including improved clearance of a broader molecular weight spectrum of uremic toxins, improvements in hemodynamic stability, anti-inflammatory effects, and correcting endothelial dysfunction.7Canaud B. Blankestijn P.J. Grooteman M.P.C. Davenport A. Why and how high volume hemodiafiltration may reduce cardiovascular mortality in stage 5 chronic kidney disease dialysis patients? a comprehensive literature review on mechanisms involved.Semin Dial. 2022; 35: 117-128Crossref PubMed Scopus (17) Google Scholar,8Lim J.-H. Park Y. Yook J.-M. et al.Randomized controlled trial of medium cut-off versus high-flux dialyzers on quality of life outcomes in maintenance hemodialysis patients.Sci Rep. 2020; 10: 7780Crossref PubMed Scopus (0) Google Scholar Previous study findings on the effects of HDF versus HD on HRQoL have been inconclusive. Some observational studies supported the assumption that HDF is accompanied by better perceived HRQoL.9Borrelli S. Minutolo R. De Nicola L. et al.Quality of life of hemodialysis patients in Central and Southern Italy: cross-sectional comparison between hemodiafiltration with endogenous reinfusion (HFR) and bicarbonate hemodialysis.G Ital Nefrol. 2016; 33 (gin/33.3.8)Google Scholar,10Knezevic M.Z. Djordjevic V.V. Radovanovic-Velickovic R.M. et al.Influence of dialysis modality and membrane flux on quality of life in hemodialysis patients.Renal Fail. 2012; 34: PubMed Scopus (0) Google Scholar A randomized controlled trial positive effects for HDF compared with HD on and aspects of A. F. A randomized trial on health-related patient with hemodiafiltration versus high-flux PubMed Scopus (0) Google Scholar a that is supported by randomized K. S. et dialysis modality quality of life in chronic hemodialysis patients? hemodialysis versus high-flux a Fail. 2013; 35: PubMed Scopus (0) Google A. L. et and outcomes hemodiafiltration compared to high-flux hemodialysis in the 2017; Full Text Full Text PDF PubMed Scopus Google Scholar the effects of HDF with HD on differences were Grooteman et of hemodiafiltration on quality of life over J 2013; PubMed Scopus Google Scholar Several studies et of hemodiafiltration on and quality of Scopus Google S. S. et comparison of quality of life for an haemodialysis and haemodiafiltration 2017; Scopus Google et trial of in high-flux hemodialysis and J Kidney Dis. 2017; 69: Full Text Full Text PDF PubMed Scopus (0) Google B. improves a study hemodialysis and 2012; PubMed Google Scholar A review from including that the was to the effect of HDF versus HD on et versus dialysis for chronic kidney an review of randomized controlled J Kidney Dis. Full Text Full Text PDF PubMed Scopus (0) Google Scholar A from reported that HDF was associated with significantly increased social compared with HDF R. et of hemodiafiltration compared with hemodialysis on quality of life in patients with a review and of randomized 2018; Scopus Google Scholar is a of from the of HDF versus HD on perceived C. B. review to the outcomes associated with the of hemodialysis versus high-flux hemodialysis hemodiafiltration (HDF) in patients with end-stage kidney disease Dial. 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The was high-dose HD with of and dialysis HDF was as a volume of in The comparison conventional HD high-flux dialysis and dialysis as standard of dialysis P.J. Fischer K.I. Barth C. et al.Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol.BMJ Open. 2020; 10e033228Crossref PubMed Scopus (46) Google P.J. C. et of hemodiafiltration or hemodialysis on mortality in kidney J PubMed Scopus Google Scholar the by the International Consortium for Health Outcomes W.R. Das-Gupta Z. Allegretti A.S. et al.Development of an international standard set of value-based outcome measures for patients with chronic kidney disease: a report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD Working Group.Am J Kidney Dis. 2019; 73: 372-384Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar applying the Patient-Reported Outcome Measurement Information System a used of the A. et Patient-Reported Outcomes Measurement Information System (PROMIS) and of health outcome Full Text Full Text PDF PubMed Scopus Google Scholar for health domains (physical function, fatigue, sleep disturbance, depression, anxiety, pain interference, and to in social and as well as a single pain et health measures of health 2019; Full Text Full Text PDF PubMed Scopus Google Scholar core domains also by the Standardized Outcomes in A. Manns B. 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Minutolo R. De Nicola L. et al.Quality of life of hemodialysis patients in Central and Southern Italy: cross-sectional comparison between hemodiafiltration with endogenous reinfusion (HFR) and bicarbonate hemodialysis.G Ital Nefrol. 2016; 33 (gin/33.3.8)Google M.Z. Djordjevic V.V. Radovanovic-Velickovic R.M. et al.Influence of dialysis modality and membrane flux on quality of life in hemodialysis patients.Renal Fail. 2012; 34: PubMed Scopus (0) Google A. F. A randomized trial on health-related patient with hemodiafiltration versus high-flux PubMed Scopus (0) Google K. S. et dialysis modality quality of life in chronic hemodialysis patients? hemodialysis versus high-flux a Fail. 2013; 35: PubMed Scopus (0) Google A. 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