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When is More Frequent Hemodialysis Beneficial?

In 2017, Medicare Administrative Contractors (MACs) began to promulgate draft local coverage determinations that include restrictive language regarding Medicare reimbursement for additional hemodialysis sessions. An important element of the draft determinations is medical justification, or the clinical conditions that constitute evidence-based rationale for the prescription of more frequent hemodialysis.

Suri and Kliger, who were both investigators in the Frequent Hemodialysis Network (FHN) trial, posed and answered this timely question in a thoughtful narrative review that appears in the July/August issue of Seminars in Dialysis. Suri and Kliger described 5 situations in which they “…believe frequent hemodialysis is likely to be most beneficial.”1

These situations are:


“FOR REDUCTION OF LEFT VENTRICULAR HYPERTROPHY, ESPECIALLY IN PATIENTS WITH MINIMAL TO NO URINE OUTPUT”

Left ventricular hypertrophy (LVH) is an adaptive response to increased cardiac work, typically caused by combined pressure and volume overload. Regression of LVH may reduce cardiovascular risk, including the incidence of heart failure, complications after myocardial infarction, and sudden arrhythmic death. 3

Diurnal and nocturnal schedules in the FHN trial reduced left ventricular mass by 14 (10%) and 11(8%) g, respectively, relative to 3 sessions per week.4,5 Comparable efficacy was observed in an earlier trial of nocturnal hemodialysis.6


“REFRACTORY VOLUME OVERLOAD AND/OR HIGH INTERDIALYTIC FLUID GAINS THAT CANNOT BE CONTROLLED ON THREE TIMES WEEKLY HEMODIALYSIS”

In hemodialysis patients, volume management involves two complementary tasks: managing interdialytic fluid load between treatments and managing ultrafiltration intensity during treatment. Although the latter task has garnered great attention in recent years, the former task is tremendously important. As measured by bioimpedance spectroscopy, chronic fluid overload is associated with 42% to 63% higher risk of death, relative to euvolemia.8

If volume cannot be adequately managed with diuretics (in patients with residual function) or dietary counseling regarding sodium and fluid intake, the most straightforward way to reduce the interdialytic fluid load may be to increase hemodialysis frequency:9 Raimann and colleagues showed that 6 versus 3 sessions per week reduced time-integrated fluid load by 3 liters/day in the FHN Daily Trial.7

If treatment hours are increased while treatment frequency is increased, then the ultrafiltration rate can simultaneously be reduced.10


“PREGNANCY”

The Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guideline for Hemodialysis Adequacy includes the following ungraded suggestion: “During pregnancy, women with end-stage kidney disease should receive long frequent hemodialysis either in-center or at home, depending on convenience.”12


“FOR PATIENTS WANTING TO TRY FREQUENT HEMODIALYSIS FOR POTENTIAL LIFESTYLE OR QUALITY OF LIFE BENEFITS”

Health-related quality of life (HRQOL) is not only associated with clinical outcomes in dialysis patients, but also highly valued by patients. In the FHN Daily Trial, 6 versus 3 sessions per week improved both physical and mental HRQOL.4 In fact, in all randomized trials of frequent versus conventional hemodialysis, frequent therapy improved both physical and mental HRQOL, despite various degrees of statistical significance.4,5,6 Notably, frequent hemodialysis sharply reduces post-dialysis recovery time.6,13


“SEVERE HYPERTENSION AND/OR SEVERE HYPERPHOSPHATEMIA THAT ARE UNCONTROLLABLE WITH THREE TIMES WEEKLY HEMODIALYSIS”

According to the most recent data from the DOPPS Practice Monitor, more than 28% of hemodialysis patients have pre-dialysis systolic blood pressure ≥160 mmHg and almost 37% of patients have 3-month mean serum phosphorus >5.5 mg/dL, despite extension application of both antihypertensive agents and phosphate binders.15 Using multiple strategies to lower blood pressure in patients on thrice-weekly hemodialysis may not lead to positive outcomes; a recently published pilot study found that patients who were randomly assigned to a lower blood pressure target range manifested higher risks of intradialytic adverse events (e.g., cramps, nausea/vomiting, and loss of consciousness), vascular access thromboses, and hospitalization.16

Frequent hemodialysis is an alternative strategy that reduces both systolic blood pressure and the need for antihypertensive agents.13 In addition, because phosphorus clearance is primarily time-dependent, frequent hemodialysis, when accompanied by more treatment hours per week, reduces serum phosphorus and the need for phosphate binders.6


Importantly, Suri and Kliger wrote that this situation “may be particularly important in patients with ongoing end-organ damage from hypertension, or calciphylaxis.”1 In other words, ongoing treatment with frequent hemodialysis may be justified, if not required.1

Conclusion

There appears to be good consensus among two teams in the nephrology community about medical justification for additional hemodialysis sessions. Multiple applications are supported by randomized clinical trials and well-designed observational cohort studies.

Suri and Kliger (2018)

Collins and Chan (2016)

Reduction of left ventricular hypertrophyIntensive Hemodialysis, Left Ventricular Hypertrophy, and Cardiovascular Disease17
Refractory volume overloadIntensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use18
PregnancyNot discussed, but supported by KDOQI clinical practice guideline12
Potential quality of life benefitsIntensive Hemodailysis and Health-Related Quality of Life19
Severe hypertensionIntensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use18
Severe hyperphosphatemiaIntensive Hemodialysis, Mineral and Bone Disorder, and Phosphate Binder Use20

Potential Risks

Not everyone will experience the reported benefits of more frequent hemodialysis. All forms of hemodialysis involve some risks. When vascular access is exposed to more frequent use, infection of the site, and other access related complications may also
be potential risks.

Certain risks associated with treatments are increased when performing solo home hemodialysis; if patients experience needles coming out, blood loss, or very low blood pressure during solo home hemodialysis, they may lose consciousness or otherwise become impaired during any health emergency which, when alone, could result in significant injury or death.

Certain risks associated with hemodialysis treatment are increased when performing nocturnal therapy due to the length of treatment time and because the patient and care partner are sleeping.

References

  1. Suri RS, Kliger AS. When is more frequent hemodialysis beneficial? Semin Dial. 2018;31:332–342. https://doi.org/10.1111/sdi.12688
  2. London, G.M., Pannier, B., Guerin, A.P. et al, Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol. 2001;12:2759–2767. https://doi.org/10.1159/000435838
  3. Mathew J, Sleight P, Lonn E, et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation. 2001;104(14):1615-1621. https://doi.org/10.1161/hc3901.096700
  4. FHN 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. https://doi.org/10.1056/NEJMoa1001593.
  5. Rocco 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. https://doi.org/10.1038/ki.2011.213.
  6. Culleton 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. https://doi.org/10.1001/jama.298.11.1291.
  7. Raimann JG, Chan CT, Daugirdas JT, et al. The Effect of Increased Frequency of Hemodialysis on Volume-Related Outcomes: A Secondary Analysis of the Frequent Hemodialysis Network Trials. Blood Purif. 2016;41(4):277-86. https://doi.org/10.1159/000441966.
  8. Zoccali C, Moissl U, Chazot C, et al. Chronic Fluid Overload and Mortality in ESRD. Journal of the American Society of Nephrology : JASN. 2017;28(8):2491-2497. https://doi.org/10.1681/ASN.2016121341.
  9. Sarafidis PA, et al. A consensus document by the EURECA-m working group of the ERA-EDTA and the Hypertension and the Kidney working group of the ESH. Journal of Hypertension. 2017 Apr; 35(4):657-676. https://doi.org/10.1097/HJH.0000000000001283.
  10. Assimon MM, Flythe JE. Rapid ultrafiltration rates and outcomes among hemodialysis patients: re-examining the evidence base. Current opinion in nephrology and hypertension. 2015;24(6):525-530. https://doi.org/10.1097/MNH.0000000000000174.
  11. Piccoli, G.B., Minelli, F., Versino, E., et al. Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes, Nephrology Dialysis Transplantation, Volume 31, Issue 11, 1 November 2016, Pages 1915–1934. https://doi.org/10.1093/ndt/gfv395
  12. National Kidney Foundation. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update. Am J Kidney Dis. 2015;66(5):884-930. https://doi.org/10.1053/j.ajkd.2015.07.015
  13. Jaber 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. 2010;56(3):531-539. https://doi.org/10.1053/j.ajkd.2010.04.019.
  14. Kotanko P, Garg AX, Depner T, et al. Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials. Hemodial Int. 2015;19(3):386-401. https://doi.org/10.1111/hdi.12255.
  15. The DOPPS Practice Monitor. http://www.dopps.org/DPM/. Accessed August 1,2018
  16. Miskulin, D.C., et al. BP in Dialysis: Results of a Pilot Study. J Am Soc Nephrol. 2018 Jan;29(1):307-316. https://doi.org/10.1681/ASN.2017020135. Epub 2017 Dec 6.
  17. McCullough, P.A., et al. Intensive Hemodialysis, Left Ventricular Hypertrophy, and Cardiovascular Disease. Am J Kidney Dis., Volume 68, Issue 5, S5 – S14.
  18. Bakris, G.L., et al. Intensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use. Am J Kidney Dis., Volume 68, Issue 5, S15 – S23.
  19. Kraus, M.A., et al. Intensive Hemodialysis and Health-Related Quality of Life. Am J Kidney Dis., Volume 68, Issue 5, S33 – S42.
  20. Bakris, G.L., et al. Intensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use. Am J Kidney Dis., Volume 68, Issue 5, S15 – S23.
  21. Copland, M., et al. Intensive Hemodialysis, Mineral and Bone Disorder, and Phosphate Binder Use. Am J Kidney Dis., Volume 68, Issue 5, S24 – S32.
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Eric Weinhandl, PhD, MS

Adjunct Assistant Professor
University of Minnesota College of Pharmacy

Clinical Epidemiologist and Statistician
NxStage Medical, Inc.

Eric Weinhandl is an epidemiologist with about 14 years of research experience in chronic kidney disease, mostly regarding dialysis and pharmaceuticals. Eric worked at the United States Renal Data System (USRDS) Coordinating Center between 2004 and 2014 and has conducted studies with Amgen, Baxter, DaVita, NxStage, Sigma Tau, and the Peer Kidney Care Initiative.

Articles by Eric Weinhandl, PhD, MS
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