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Daily Home Hemodialysis: Balancing Cardiovascular Benefits With Infectious Harms

2014; Elsevier BV; Volume: 65; Issue: 1 Linguagem: Inglês

10.1053/j.ajkd.2014.08.012

1523-6838

Annie‐Claire Nadeau‐Fredette, Sunil V. Badve, David W. Johnson,

Acute Kidney Injury Research

Related Article, p. 98 Related Article, p. 98 Current standard hemodialysis (HD) regimens, consisting of 3- to 5-hour sessions performed thrice weekly, are associated with persistently high morbidity and mortality rates.1Collins A.J. Foley R.N. Chavers B. et al.US Renal Data System 2013 annual data report.Am J Kidney Dis. 2014; 63: e1-e420Google Scholar, 2Marshall 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: 782-793Google Scholar, 3Tentori 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: 4180-4188Google Scholar Although higher dialysis dose and membrane flux have not been shown to appreciably improve these poor outcomes,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: 2010-2019Google Scholar enhanced HD frequency and/or duration recently have gained popularity as a potential strategy for achieving better results for patients with end-stage renal disease (ESRD).5Jayanti A, Morris J, Stenvinkel P, Mitra S. Home hemodialysis: beliefs, attitudes, and practice patterns [published online ahead of print May 11, 2014]. Hemodial Int. http://dx.doi.org/10.1111/hdi.12176.Google Scholar, 6Mehrotra R. Himmelfarb J. Dialysis in 2012: could longer and more frequent haemodialysis improve outcomes?.Nat Rev Nephrol. 2013; 9: 74-75Google Scholar In particular, daily home HD (DHHD), mostly performed as short-daily HD, generally has been found in randomized and nonrandomized studies to be associated with improved surrogate clinical outcomes, including reduction in blood pressure or need for antihypertensive medication7Zimmerman D.L. Ruzicka M. Hebert P. Fergusson D. Touyz R.M. Burns K.D. Short daily versus conventional hemodialysis for hypertensive patients: a randomized cross-over study.PLoS One. 2014; 9: e97135Google Scholar, 8Nesrallah G. Suri R. Moist L. Kortas C. Lindsay R.M. Volume control and blood pressure management in patients undergoing quotidian hemodialysis.Am J Kidney Dis. 2003; 42: 13-17Google Scholar, 9Chertow 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: 2287-2300Google Scholar and improvements in quality of life,10Jaber B.L. Lee Y. Collins A.J. et al.Effect of daily hemodialysis on depressive symptoms and postdialysis recovery time: interim report from the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study.Am J Kidney Dis. 2010; 56: 531-539Google Scholar, 11Unruh M.L. Larive B. Chertow G.M. et al.Effects of 6-times-weekly versus 3-times-weekly hemodialysis on depressive symptoms and self-reported mental health: Frequent Hemodialysis Network (FHN) Trials.Am J Kidney Dis. 2013; 61: 748-758Google Scholar, 12Heidenheim A.P. Muirhead N. Moist L. Lindsay R.M. Patient quality of life on quotidian hemodialysis.Am J Kidney Dis. 2003; 42: 36-41Google Scholar cardiac geometry and rate,13Chan C.T. Chertow G.M. Daugirdas J.T. et al.Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial.Nephrol Dial Transplant. 2014; 29: 168-178Google Scholar, 14Chan 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: 251-261Google Scholar and serum phosphate control.9Chertow 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: 2287-2300Google Scholar, 15Jaber B.L. Schiller B. Burkart J.M. et al.Impact of short daily hemodialysis on restless legs symptoms and sleep disturbances.Clin J Am Soc Nephrol. 2011; 6: 1049-1056Google Scholar The Frequent Hemodialysis Network daily and nocturnal randomized controlled trials9Chertow 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: 2287-2300Google Scholar, 16Rocco M.V. Lockridge Jr., R.S. Beck G.J. et al.The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.Kidney Int. 2011; 80: 1080-1091Google Scholar and a Canadian randomized controlled trial by Culleton et al17Culleton 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: 1291-1299Google Scholar showed that daily HD resulted in significant improvements in left ventricular mass and quality of life compared with thrice-weekly intermittent HD. Despite these observed benefits, there also is evidence that frequent HD may be associated with increased risk of adverse effects, including infection, vascular access events, and loss of residual kidney function.18Daugirdas J.T. Greene T. Rocco M.V. et al.Effect of frequent hemodialysis on residual kidney function.Kidney Int. 2013; 83: 949-958Google Scholar, 19Suri R.S. Larive B. Sherer S. et al.Risk of vascular access complications with frequent hemodialysis.J Am Soc Nephrol. 2013; 24: 498-505Google Scholar, 20Jun M. Jardine M.J. Gray N. et al.Outcomes of extended-hours hemodialysis performed predominantly at home.Am J Kidney Dis. 2013; 61: 247-253Google Scholar Concerns that patients treated with home HD are at higher risk for infection, possibly related to more frequent access cannulation, particular cannulation methods (especially the buttonhole technique), and lesser scrutiny of infection control practices at home, are supported by observational studies,21Nesrallah G.E. Cuerden M. Wong J.H. Pierratos A. Staphylococcus aureus bacteremia and buttonhole cannulation: long-term safety and efficacy of mupirocin prophylaxis.Clin J Am Soc Nephrol. 2010; 5: 1047-1053Google Scholar, 22Van Eps C.L. Jones M. Ng T. et al.The impact of extended-hours home hemodialysis and buttonhole cannulation technique on hospitalization rates for septic events related to dialysis access.Hemodial Int. 2010; 14: 451-463Google Scholar randomized controlled trials,23Vaux E. King J. Lloyd S. et al.Effect of buttonhole cannulation with a polycarbonate PEG on in-center hemodialysis fistula outcomes: a randomized controlled trial.Am J Kidney Dis. 2013; 62: 81-88Google Scholar, 24Chow J. Rayment G. San Miguel S. Gilbert M. A randomised controlled trial of buttonhole cannulation for the prevention of fistula access complications.J Ren Care. 2011; 37: 85-93Google Scholar, 25MacRae J.M. Ahmed S.B. Atkar R. Hemmelgarn B.R. A randomized trial comparing buttonhole with rope ladder needling in conventional hemodialysis patients.Clin J Am Soc Nephrol. 2012; 7: 1632-1638Google Scholar and a recent systematic review.26Muir C.A. Kotwal S.S. Hawley C.M. et al.Buttonhole cannulation and clinical outcomes in a home hemodialysis cohort and systematic review.Clin J Am Soc Nephrol. 2014; 9: 110-119Google Scholar Consequently, the uncertain balance of benefits and harms of DHHD has fueled clinician anxiety regarding the feasibility of home HD programs, which often include extended or frequent HD.27Tong A. Palmer S. Manns B. et al.Clinician beliefs and attitudes about home haemodialysis: a multinational interview study.BMJ Open. 2012; 2Google Scholar In this issue of AJKD, Weinhandl et al28Weinhandl E.D. Nieman K.M. Gilberstin D.T. Collins A.J. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients.Am J Kidney Dis. 2015; 65: 98-108Google Scholar report hospitalization outcomes in a retrospective observational cohort study. The study compares 3,480 incident patients with ESRD treated with DHHD (5-6 sessions per week, using NxStage System One between January 2006 and December 2009) with contemporary, propensity score–matched, US Renal Data System–registered patients with ESRD treated with facility-based conventional thrice-weekly HD. (Only patients with Medicare primary payer coverage were included in the study.) Thrice-weekly HD controls were matched 5 to 1 with DHHD cases using a propensity score incorporating dialysis start date, ESRD duration, hospitalization history, and dialysis provider. Using intention-to-treat analysis, no difference was observed between patients receiving DHHD and thrice-weekly HD with respect to the primary outcome of all-cause hospital admission (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.98-1.03). Interestingly, cause-specific hospitalizations were significantly different between the 2 groups, such that DHHD was associated with a lower hazard of hospital admissions for cardiovascular disease (HR, 0.89; 95% CI, 0.86-0.93) but a higher hazard of infection-related hospital admissions (HR, 1.18; 95% CI, 1.13-1.23). Overall, infection-related admissions outnumbered cardiovascular admissions in the DHHD group in both eras, with 48.5 versus 36.4 (2006-2007) and 54.4 versus 40.3 admissions per 100 patient-years (2008-2009), respectively. When subcategories of cardiovascular admissions were examined, the observed benefit of DHHD was limited to heart failure/fluid overload/cardiomyopathy and hypertensive disease, with no impact on admissions due to ischemic heart disease, cerebrovascular disease, peripheral vascular disease, or arrhythmia. These findings suggest that the benefit of DHHD for cardiovascular admissions was due predominantly to better fluid control and that DHHD did not mitigate ischemic and arrhythmic cardiovascular risks. However, the DHHD group experienced more infection-related hospital admissions due to bacteremia and sepsis, cardiac infection, osteomyelitis, and vascular access infection, suggesting that the increased risk of infection-related complications was mainly dialysis or access related. Interestingly, compared with matched patients receiving thrice-weekly HD, those treated with DHHD were at higher risk of infection-related first admission, but not of readmission (after discharge). Although the authors did not provide details regarding the infection control protocols in these units during the observed times, it is possible that DHHD patients who survived an initial admission in this study received refresher courses, improved their cannulation technique, or adhered more carefully to infection prevention protocols, subsequently modifying their risk of infection. Alternatively, it is possible that that the similar risk of infection-related readmission arose because infection-related admissions led to DHHD technique failure. Thus, in intention-to-treat analysis, patients treated with thrice-weekly HD would be included in the DHHD group when examining readmissions, and for on-treatment analysis, only the “survivors” still on DHHD therapy would be included in the assessment of readmission hazard. Using the admission rates in the intention-to-treat analysis for patients from the most recent era (2008-2009), we calculate that 19 patients needed to perform DHHD for 1 year to prevent one cardiovascular-related hospital admission; however, only 12 patients needed to perform DHHD for 1 year to cause one infection-related hospital admission.29Stang A. Poole C. Bender R. Common problems related to the use of number needed to treat.J Clin Epidemiol. 2010; 63: 820-825Google Scholar Thus, the presence of cardiovascular benefits occurred at the cost of increased infections, which is entirely consistent with the emerging literature in intensive dialysis.9Chertow 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: 2287-2300Google Scholar, 16Rocco M.V. Lockridge Jr., R.S. Beck G.J. et al.The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.Kidney Int. 2011; 80: 1080-1091Google Scholar, 20Jun M. Jardine M.J. Gray N. et al.Outcomes of extended-hours hemodialysis performed predominantly at home.Am J Kidney Dis. 2013; 61: 247-253Google Scholar Although these results give considerable pause for thought, it is important to note that the study by Weinhandl et al28Weinhandl E.D. Nieman K.M. Gilberstin D.T. Collins A.J. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients.Am J Kidney Dis. 2015; 65: 98-108Google Scholar had a number of important limitations, not the least of which was the potential issue of indication bias with residual confounding. The authors went through a meticulous matching process to minimize discrepancies between DHHD and thrice-weekly HD patients, but no matching or adjusting technique can eliminate all unmeasured bias; other studies of home HD2Marshall 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: 782-793Google Scholar, 30Weinhandl E.D. Liu J. Gilbertson D.T. Arneson T.J. Collins A.J. Survival in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients.J Am Soc Nephrol. 2012; 23: 895-904Google Scholar, 31Nesrallah 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: 696-705Google Scholar have shown that patients treated with DHHD are younger, more likely to be white and male, and less likely to have comorbid conditions than patients receiving thrice-weekly HD. Furthermore, Weinhandl et al28Weinhandl E.D. Nieman K.M. Gilberstin D.T. Collins A.J. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients.Am J Kidney Dis. 2015; 65: 98-108Google Scholar did not report specific dialysis parameters (frequency, duration, dose, or timing [nocturnal vs daytime]), infection control practices, access types, or cannulation techniques, all of which would have been helpful for exploratory analyses. Moreover, diagnosis codes were used to classify admissions, potentially leading to coding bias. In addition, the generalizability of the study’s findings is limited because the study was restricted to Medicare-enrolled DHHD patients treated solely with NxStage System One technology in a country with high background rates of HD catheter use. Also, although little is known about admissions among home HD patients, the rate and number of days of all-cause admissions were more than 3 times higher in this study than those reported in a Canadian cohort of patients receiving nocturnal HD,32Tennankore K.K. Kim S.J. Baer H.J. Chan C.T. Survival and hospitalization for intensive home hemodialysis compared with kidney transplantation.J Am Soc Nephrol. 2014; 25: 2113-2120Google Scholar thereby raising further doubts about the generalizability of the study’s findings. Finally, while it is acknowledged that mortality was not a study objective per se, it would have been useful for the investigators to include mortality data, especially death after hospitalization, as a surrogate marker of acute illness severity. Taking all these factors into account, what are the implications for clinical practice of the study by Weindhandl et al?28Weinhandl E.D. Nieman K.M. Gilberstin D.T. Collins A.J. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients.Am J Kidney Dis. 2015; 65: 98-108Google Scholar First and foremost, the cumulative findings of the limited flawed investigations to date clearly suggest that DHHD is not a panacea for the treatment of chronic kidney failure, but instead is a viable option for renal replacement therapy that, as currently practiced, offers a comparable trade-off between cardiovascular benefit and infectious harm. This important consideration must be communicated adequately to patients and their families to help them make informed decisions regarding dialysis modality. Moreover, it is critical that further clinical and research efforts are undertaken to mitigate the heightened risk of infection in the home HD setting, through better patient selection, infection control surveillance and practices, and continuous quality improvement programs. In particular, research efforts should focus on areas such as topical antimicrobial prophylaxis (eg, mupirocin or antibacterial honey), access cleansing agents and dressings, cannulation methods (buttonhole vs rope ladder), needle type (metal vs plastic), needle anchorage techniques, training and refresher protocols, dialysis timing (daytime vs night-time), and optimal home dialysis session frequency (daily vs alternate daily). In many respects, the infectious harm challenges facing home HD patients are not dissimilar from those facing patients using the other home dialysis modality, peritoneal dialysis. Even so, progress made in understanding infectious harm in the home HD setting has been far more limited to date, as evidenced by the paucity of relevant research literature. Needless to say, further endeavours in minimizing infection risk during home HD are crucial to the more widespread application of this important dialysis modality. Support: None. Financial Disclosure: Dr Nadeau-Fredette is supported by a Baxter Healthcare Clinical Evidence Council research grant. Dr Johnson has received consultancy fees, speakers honoraria, travel sponsorships, and research grants from Baxter Healthcare and Fresenius Medical Care and is a current recipient of a Queensland Government Health Research Fellowship. Dr Badve declares that he has no relevant financial interests. Hospitalization in Daily Home Hemodialysis and Matched Thrice-Weekly In-Center Hemodialysis PatientsAmerican Journal of Kidney DiseasesVol. 65Issue 1PreviewCardiovascular disease is a common cause of hospitalization in dialysis patients. Daily hemodialysis improves some parameters of cardiovascular function, but whether it associates with lower hospitalization risk is unclear. Full-Text PDF