Improving Outcomes for Dialysis Patients

Recent Trials Show Promising Benefits

Advancing Dialysis

The long interdialytic interval, commonly referred to as the “2-day killer gap,” is a time of heightened risk of mortality and morbidity in conventional hemodialysis.

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The long interdialytic interval, commonly referred to as the 2-day “killer gap,” is a time of heightened risk of mortality and morbidity with conventional hemodialysis; rates of death and cardiovascular hospitalization were 23% and 124% higher after the gap, respectively, than on other days.1

Chapter 1, Figure 1:Rates of death and cardiovascular hospitalization on the day after the 2-day gap in dialysis treatment and on all others days.1

1Foley, R. N., Gilbertson, D. T., Murray, T., & Collins, A. J. (2011). Long interdialytic interval and mortality among patients receiving hemodialysis. New England Journal of Medicine, 365(12),1099-1107.

Cardiovascular-related deaths in prevalent dialysis patients are common. Over 41% of all deaths were cardiovascular-related, with nearly identical percentages in hemodialysis and peritoneal dialysis patients.2

Chapter 1, Figure 2:Distribution of primary cause of death in hemodialysis patients, 2011 to 2013.2

2Saran R, Li Y, Robinson B, et al. US Renal Data System 2014 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis Off J Natl Kidney Found. 2015;66(1 Suppl 1):Svii, S1-305. doi:10.1053/j.ajkd.2015.05.001

Multiple randomized clinical trials show intensive hemodialysis significantly reduces left ventricular mass.1,2,3

Chapter 1, Figure 3:Effects of intensive versus conventional hemodialysis on left ventricular mass in the FHN Daily Trial,1 the FHN Nocturnal Trial,2 and the Canadian trial of nocturnal hemodialysis.3 Estimated treatment effects (solid dots) and associated 95% confidence intervals (solid lines) are displayed at the bottom.

1FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300. doi:10.1056/NEJMoa1001593. 2Rocco MV, Lockridge RS, Beck GJ, et al. The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int.2011;80(10):1080-1091. doi:10.1038/ki.2011.213. 3Culleton BF, Walsh M, Klarenbach SW, 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(11):1291-1299. doi:10.1001/jama.298.11.1291.

Short daily hemodialysis (SDHD) was associated with lower risk of cardiovascular-related hospitalization, compared to conventional in-center hemodialysis (CIHD). In particular, SDHD was associated with significantly lower risks of hospitalization due to cerebrovascular disease, heart failure/fluid overload, and hypertensive disease.1

Chapter 1, Figure 4:Relative hazards of cause-specific cardiovascular hospitalization for short daily hemodialysis versus in-center hemodialysis1 and versus peritoneal dialysis.2 Sold lines represent 95% confidence intervals around estimated hazard ratios (solid dots). Abbreviations: IHD, in-center hemodialysis; PD, peritoneal dialysis; SDHD, short daily hemodialysis.

1Weinhandl ED, Nieman KM, Gilbertson DT, Collins AJ. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients. Am J Kidney Dis Off J Natl Kidney Found. 2015;65(1):98-108. doi:10.1053/j.ajkd.2014.06.015. 2Weinhandl ED, Gilbertson DT, Collins AJ. Mortality, Hospitalization, and Technique Failure in Daily Home Hemodialysis and Matched Peritoneal Dialysis Patients: A Matched Cohort Study. Am J Kidney Dis Off J Natl Kidney Found. 2016;67(1):98-110. doi:10.1053/j.ajkd.2015.07.014.

Short daily hemodialysis (SDHD) was also associated with lower risks of cardiovascular-related hospitalization, compared to peritoneal dialysis (PD).2

Chapter 1, Figure 4:Relative hazards of cause-specific cardiovascular hospitalization for short daily hemodialysis versus in-center hemodialysis1 and versus peritoneal dialysis.2 Sold lines represent 95% confidence intervals around estimated hazard ratios (solid dots). Abbreviations: IHD, in-center hemodialysis; PD, peritoneal dialysis; SDHD, short daily hemodialysis.

1Weinhandl ED, Nieman KM, Gilbertson DT, Collins AJ. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients. Am J Kidney Dis Off J Natl Kidney Found. 2015;65(1):98-108. doi:10.1053/j.ajkd.2014.06.015. 2Weinhandl ED, Gilbertson DT, Collins AJ. Mortality, Hospitalization, and Technique Failure in Daily Home Hemodialysis and Matched Peritoneal Dialysis Patients: A Matched Cohort Study. Am J Kidney Dis Off J Natl Kidney Found. 2016;67(1):98-110. doi:10.1053/j.ajkd.2015.07.014.

Despite substantial use of multiple antihypertensive agents, over 60% of hemodialysis patients have elevated pre-dialysis blood pressure.1

Chapter 2, Figure 1:Distribution of pre-dialysis systolic bloodpressure in the Dialysis Outcomes andPractice Patterns Study Practice Monitor,December 2015.1

1The DOPPS Practice Monitor. http://www.dopps.org/DPM/. Accessed May 20, 2015.

Multiple randomized clinical trials show intensive hemodialysis significantly lowers blood pressure.1,2,3

Chapter 2, Figure 2:Effects of intensive versus conventionalhemodialysis on pre-dialysis systolicblood pressure in the FHN Daily Trial,1

the FHN Nocturnal Trial,2 and theCanadian trial of nocturnal hemodialysis.3

Estimated treatment effects (solid dots)and associated 95% confidence intervals(solid lines) are displayed at the bottom.

1FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300. doi:10.1056/NEJMoa1001593. 2Rocco MV, Lockridge RS, Beck GJ, et al. The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int. 2011;80(10):1080-1091. doi:10.1038/ki.2011.213. 3Culleton BF, Walsh M, Klarenbach SW, 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(11):1291-1299. doi:10.1001/jama.298.11.1291.

In the FHN Daily Trial, the number of antihypertensive medications perpatient declined from 2.2 to 1.4. In trials of nocturnal hemodialysis, thenumber of antihypertensive medications per patients decreased similarly.1,2

Chapter 2, Figure 3:Mean number of prescribed antihypertensive medications at baseline, at month 4, and at month 12 of the FHN Daily Trial.1 Dashed bars span one standard deviation above and below the mean.

1Kotanko P, Garg AX, Depner T, et al. Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials. Hemodial Int Int Symp Home Hemodial. 2015;19(3):386-401. doi:10.1111/hdi.12255.

In 2015, over 36% of hemodialysis patients had serum phosphorus levels persistently above the target range with an additional 15% to 20% of patients with serum phosphorus levels between 5.0 and 5.5 mg/dL, an interval associated with increased cardiovascular risk.

Chapter 3, Figure 1:Distribution of 3-month mean serumphosphorus in the Dialysis Outcomes andPractice Patterns Study Practice Monitor,December 2015.

1The DOPPS Practice Monitor. http://www.dopps.org/DPM/. Accessed May 20, 2015.

Under perfect adherence, the cost of phosphate binders to all payers would be enormous.1 Medicare Part D expenditures for phosphate binders were noticeably higher in a large dialysis provider organization that delivers integrated pharmacy services to support medication adherence. Already, Medicare Part D expenditures for phosphate binders and calcimimetics exceed $1 billion annually.2

Chapter 3, Figure 2:Medicare Part D gross costs per patient-year for phosphate binders, by dialysis provider organization or class, 2011. Abbreviations: FDF, free-standing dialysis facility; HDF, hospital-based dialysis facility; SDO, small dialysis organization.

1Collins AJ, Foley RN, Chavers B, et al. US Renal Data System 2013 Annual Data Report. Am J Kidney Dis Off J Natl Kidney Found. 2014;63(1 Suppl):A7. doi:10.1053/j.ajkd.2013.11.001. 2Saran R, Li Y, Robinson B, et al. US Renal Data System 2015 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis Off J Natl Kidney Found. 2016;67(3 Suppl 1):A7-A8. doi:10.1053/j.ajkd.2015.12.014.

The FHN Daily Trial, FHN Nocturnal Trial and a Canadian trial of nocturnal hemodialysis reported reductions in mean serum phosphorus of 11%, 18% and 20% respectively, from baseline to follow-up. In the conventional hemodialysis group, serum phosphorus increased over time.1,2

Chapter 3, Figure 3:Effects of intensive versus conventional hemodialysis on serum phosphorus in the FHN Daily Trial,1 the FHN Nocturnal Trial,1 and the Canadian trial of nocturnal hemodialysis.2 Estimated treatment effects (solid dots) and associated 95%confidence intervals (solid lines) are displayed at the bottom.

1Daugirdas JT, Chertow GM, Larive B, et al. Effects of frequent hemodialysis on measures of CKD mineral and bone disorder. J Am Soc Nephrol JASN. 2012;23(4):727-738. doi:10.1681/ASN.2011070688. 2Culleton BF, Walsh M, Klarenbach SW, 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(11):1291-1299. doi:10.1001/jama.298.11.1291.

In the FHN Daily Trial, mean estimated pill burden per day declined 20% withintensive hemodialysis, from 7.17 pills per day at baseline to 5.70 after 10 to12 months of follow-up.

Chapter 3, Figure 4:Mean equivalent phosphorus bindingdose for intensive versus conventionalhemodialysis in the FHN Daily Trial.Dashed bars span one standard deviationabove and below the mean.

1Daugirdas JT, Chertow GM, Larive B, et al. Effects of frequent hemodialysis on measures of CKD mineral and bone disorder. J Am Soc Nephrol JASN. 2012;23(4):727-738. doi:10.1681/ASN.2011070688.

In the FHN Nocturnal Trial, the percentage of patients using any phosphate binders decreased with intensive hemodialysis, from 97% at baseline to 27% after 10 to 12 months.

Chapter 3, Figure 5:Distribution of equivalent phosphorusbinding dose (EPBD) for intensive versusconventional hemodialysis in the FHNNocturnal Trial.1

1Daugirdas JT, Chertow GM, Larive B, et al. Effects of frequent hemodialysis on measures of CKD mineral and bone disorder. J Am Soc Nephrol JASN. 2012;23(4):727-738. doi:10.1681/ASN.2011070688.

Intensive hemodialysis improved physical health-related quality of life in threerandomized clinical trials, although the statistical significance of individualeffects varied.1,2,3

Chapter 4, Figure 1:Effects of intensive versus conventionalhemodialysis on the physical-healthcomposite score in the FHN Daily Trial,1

the FHN Nocturnal Trial,2 and theCanadian trial of nocturnal hemodialysis.3

Estimated treatment effects (solid dots)and associated 95% confidence intervals(solid lines) are displayed at the bottom.

1FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300. doi:10.1056/NEJMoa1001593. 2Rocco MV, Lockridge RS, Beck GJ, et al. The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int. 2011;80(10):1080-1091. doi:10.1038/ki.2011.213. 3Manns BJ, Walsh MW, Culleton BF, et al. Nocturnal hemodialysis does not improve overall measures of quality of life compared to conventional hemodialysis. Kidney Int. 2009;75(5):542-549. doi:10.1038/ki.2008.639.

Intensive hemodialysis also improved mental health-related quality of life in three randomized clinical trials, although the statistical significance of individual effects varied.1,2,3

Chapter 4, Figure 2:Effects of intensive versus conventionalhemodialysis on the physical-healthcomposite score in the FHN Daily Trial,1

the FHN Nocturnal Trial,2 and theCanadian trial of nocturnal hemodialysis.3

Estimated treatment effects (solid dots)and associated 95% confidence intervals(solid lines) are displayed at the bottom.

1Unruh ML, Larive B, Chertow GM, 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 Off J Natl Kidney Found. 2013;61(5):748-758. doi:10.1053/j.ajkd.2012.11.047. 2Manns BJ, Walsh MW, Culleton BF, et al. Nocturnal hemodialysis does not improve overall measures of quality of life compared to conventional hemodialysis. Kidney Int. 2009;75(5):542-549. doi:10.1038/ki.2008.639.

In the FHN trials, intensive hemodialysis decreased Beck Depression Inventory scores more so than conventional hemodialysis.1,2

Chapter 4, Figure 3:Effects of intensive versus conventionalhemodialysis on the Beck DepressionInventory score in the FHN Daily Trial1and the FHN Nocturnal Trial.2 Estimatedtreatment effects (solid dots) and associated 95% confidence intervals (solid lines) are displayed at the bottom.

1FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300. doi:10.1056/NEJMoa1001593. 2Rocco MV, Lockridge RS, Beck GJ, et al. The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int. 2011;80(10):1080-1091. doi:10.1038/ki.2011.213.

Many of the most commonly reported symptoms among hemodialysis patients, including fatigue, drops in blood pressure, and cramping have also been identified by patients and care partners as being more important thanlife expectancy.1,2

Chapter 5, Figure 1:Prevalence of commonly reportedsymptoms in a cohort of 550hemodialysis patients.2

1Caplin B, Kumar S, Davenport A. Patients’ perspective of haemodialysis-associated symptoms. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2011;26(8):2656-2663. doi:10.1093/ndt/gfq763. 2Urquhart-Secord R, Craig JC, Hemmelgarn B, et al. Patient and Caregiver Priorities for Outcomes in Hemodialysis: An International Nominal Group Technique Study. Am J Kidney Dis Off J Natl Kidney Found. March 2016. doi:10.1053/j.ajkd.2016.02.037.

The cumulative incidence of intradialytic hypotension was significantly lower with intensive hemodialysis in both of the FHN Trials compared to conventional hemodialysis.1

Chapter 5, Figure 2:Incidence of levels I, II, and III intradialytic hypotension for intensive versus conventional hemodialysis in the FHN Daily Trial and the FHN Nocturnal Trial.1

Symptoms of intradialytic hypotension were classified into 3 categories: those that led to lowering of the UF rate or reduced blood flow (Level I); those that led to the administration of saline, but not to lowering of the UF rate (Level II); and those that led to both the administrationof saline and lowering of the UF rate (Level III).

1Kotanko P, Garg AX, Depner T, et al. Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials. Hemodial Int Int Symp Home Hemodial. 2015;19(3):386-401. doi:10.1111/hdi.12255.

Each 1-hour increment in post-dialysis recovery time was associated with significantly increased risks of death and hospitalization.1

Chapter 5, Figure 3:Distribution of post-dialysis recoverytime in the DOPPS.1

Recovery time was from 2 to 6 hours in 41% of patients, from 6 to 12 hours in 17% of patients, and greater than 12 hours in 10% of patients.

1Rayner HC, Zepel L, Fuller DS, et al. Recovery time, quality of life, and mortality in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis Off J Natl Kidney Found. 2014;64(1):86-94. doi:10.1053/j.ajkd.2014.01.014.

In FREEDOM Study, mean post-dialysis recovery time fell from 7.9 hours at baseline to 1.0 hours at 4 months, and to 1.1 hours at 12 months. Moreover, the percentage of patients with recovery time less than 1 hour increased from 19% at baseline to 65% after 12 months.1

Chapter 5, Figure 4:Mean post-dialysis recovery time inintention-to-treat and per-protocolcohorts of the FREEDOM study.1

Dashed bars span one standarddeviation above and below the mean.

1Jaber BL, Lee Y, Collins AJ, 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 Off J Natl Kidney Found. 2010;56(3):531-539. doi:10.1053/j.ajkd.2010.04.019.

Infection appears to be more likely with intensive hemodialysis,although the relative importance of frequency versus setting meritsfurther investigation.1,2,3,4,5

Chapter 6, Figure 1:Relative hazards of cause-specificinfection-related hospitalization for short daily hemodialysis versus conventional in-center hemodialysis1 and versus peritoneal dialysis.2 Abbreviations: CIHD, in-center hemodialysis; PD, peritoneal dialysis; SDHD, short daily hemodialysis.

1Weinhandl ED, Nieman KM, Gilbertson DT, Collins AJ. Hospitalization in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients. Am J Kidney Dis Off J Natl Kidney Found. 2015;65(1):98-108. doi:10.1053/j.ajkd.2014.06.015. 2Weinhandl ED, Gilbertson DT, Collins AJ. Mortality, Hospitalization, and Technique Failure in Daily Home Hemodialysis and Matched Peritoneal Dialysis Patients: A Matched Cohort Study. Am J Kidney Dis Off J Natl Kidney Found. 2016;67(1):98-110. doi:10.1053/j.ajkd.2015.07.014. 3FHN Trial Group, Chertow GM, Levin NW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300. doi:10.1056/NEJMoa1001593. 4Rocco MV, Lockridge RS, Beck GJ, et al. The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int. 2011;80(10):1080-1091. doi:10.1038/ki.2011.213. 5Spry LA, Burkart JM, Holcroft C, Mortier L, Glickman JD. Survey of home hemodialysis patients and nursing staff regarding vascular access use and care. Hemodial Int Int Symp Home Hemodial. 2015;19(2):225-234. doi:10.1111/hdi.12211.