Advancing dialysis - Improving Outcomes for Dialysis Patients

1. Improving Outcomes
for Dialysis Patients
Recent Trials Show Promising Benefits

2. 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.
Find out more at our website.

3. 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.

4. 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

5. 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.

6. 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.

7. 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.

8. 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 blood
pressure in the Dialysis Outcomes and
Practice Patterns Study Practice Monitor,
December 2015.1
1The DOPPS Practice Monitor. http://www.dopps.org/DPM/. Accessed May 20, 2015.

9. Multiple randomized clinical trials show
intensive hemodialysis significantly
lowers blood pressure.1,2,3
Chapter 2, Figure 2:
Effects of intensive versus conventional
hemodialysis on pre-dialysis systolic
blood pressure 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.

10. In the FHN Daily Trial, the number
of antihypertensive medications per
patient declined from 2.2 to 1.4.
In trials of nocturnal hemodialysis, the
number 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.

11. 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 serum
phosphorus in the Dialysis Outcomes and
Practice Patterns Study Practice Monitor,
December 2015.
1The DOPPS Practice Monitor. http://www.dopps.org/DPM/. Accessed May 20, 2015.

12. 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.

13. 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.

14. In the FHN Daily Trial, mean estimated
pill burden per day declined 20% with
intensive hemodialysis, from 7.17 pills
per day at baseline to 5.70 after 10 to
12 months of follow-up.
Chapter 3, Figure 4:
Mean equivalent phosphorus binding
dose for intensive versus conventional
hemodialysis in the FHN Daily Trial.
Dashed bars span one standard deviation
above 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.

15. 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 phosphorus
binding dose (EPBD) for intensive versus
conventional hemodialysis in the FHN
Nocturnal 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.

16. Intensive hemodialysis improved physical
health-related quality of life in three
randomized clinical trials, although the
statistical significance of individual
effects varied.1,2,3
Chapter 4, Figure 1:
Effects of intensive versus conventional
hemodialysis on the physical-health
composite score 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. 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.

17. 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 conventional
hemodialysis on the physical-health
composite score 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.
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.

18. 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 conventional
hemodialysis on the Beck Depression
Inventory score in the FHN Daily Trial1
and the FHN Nocturnal Trial.2 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.

19. 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 than
life expectancy.1,2
Chapter 5, Figure 1:
Prevalence of commonly reported
symptoms in a cohort of 550
hemodialysis 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.

20. 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 administration
of 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.

21. 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 recovery
time 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.

22. 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 in
intention-to-treat and per-protocol
cohorts of the FREEDOM study.1
Dashed bars span one standard
deviation 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.

23. Infection appears to be more
likely with intensive hemodialysis,
although the relative importance
of frequency versus setting merits
further investigation.1,2,3,4,5
Chapter 6, Figure 1:
Relative hazards of cause-specific
infection-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.