Twice vs Thrice Weekly Incident Hemodialysis in Elderly Patients

A Pragmatic Randomized Clinical Trial: Twice-weekly vs Thrice-weekly Incident hemoDialysis in Elderly Patients

As Korea is becoming a super-aged society, the number of elderly patients with end-stage kidney disease (ESKD) is expected to increase rapidly. Therefore, the burden on Korean society will also increase.

Thrice-weekly hemodialysis is standard for renal replacement therapy. However, this regimen has not been validated for elderly ESKD patients with residual renal function. Elderly patients can have multiple comorbidities such as hypertension, diabetes, cardiovascular disease, and impaired physical activity. Frequent hemodialysis could provoke falls, hypotension, and cognitive impairment. Previous reports have suggested the potential benefit of twice-weekly hemodialysis with incremental increases in frequency when residual renal function decreases. In addition, twice-weekly hemodialysis decreases hospitalization rates in frail patients.

Therefore, the investigators hypothesized initiating renal replacement therapy with twice-weekly hemodialysis decreases the hopsitalizatoin rates compared with conventional thrice-weekly hemodialysis in elderly ESRD patients with residual renal function. This study is a pragmatic randomized clinical trial, multicenter study. Study subjects are incident ESRD patients (>= 60 years old, n=428) with residual urine volume ( > 500 mL/day) and follow up up to 2 years. Twice-weekly hemodialysis could be incremented according to clinical situations such as volume overload, hyperkalemia and uremic symptom. Primary outcome of this study is hospitalization rate during follow-up. Secondary outcomes include dialysis related hospitalization rate, the length of hospital stay, complication of dialysis,mortality rate and assessments of quality of life, frailty, and cost-utility.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Frailty; Age Problem; Dialysis; Complications
• Intervention / Treatment: Other: Hemodialysis

Detailed Description

End-stage kidney disease (ESKD) poses a substantial public health challenge, with the number of patients requiring renal replacement therapy (RRT) globally reaching 2.61 million in 2010 and projected to rise to 5.43 million by 2030. In Korea, the incidence of hemodialysis (HD) has also been gradually increasing. The increase in HD incidence in South Korea is significantly linked to the aging population. Korea is one of the most rapidly aging countries in the world and the age of dialysis patients is also increasing, with more than half over the age of 60.

HD has potential advantages over conservative management or peritoneal dialysis in older adults, however, guidelines for optimal HD for the elderly have not yet been established. Typically, patients receive HD three times a week, with only a small proportion of patients receiving less frequent dialysis. However, potential disadvantages such as hemodynamic stress, vascular access problems, bleeding, falls and economic cost should be considered in older adults with ESKD.

In elderly patients, it is often difficult to maintain a thrice-weekly HD schedule due to the presence of other medical conditions and the challenges of frailty. Elderly patients have shown poor outcome even after initiation of HD. A study by Santos et al. demonstrated a more than twofold increased risk of mortality at 6 months in patients older than 75 years compared to those younger than 75. Another study using Japanese National Dialysis Registry data revealed a 30% mortality rate in those aged over 80 years within 1 year after initiation of HD, with frailty being one of the most important factors associated with early death after initiation of HD. Excessive HD in elderly patients can lead to malnutrition, low blood pressure during dialysis, poor quality of life, depression, and stress due to physical and temporal activity restriction. The increased risk of falls in HD patients is also a serious problem.

Incremental initiation of HD involves starting HD at a lower intensity than the standard 4 hours thrice weekly and gradually increasing the frequency and duration of dialysis as kidney function declines. The decision to initiate patients on incremental HD can be made based on clinical parameters such as urine volume or residual kidney function, socio-economic factors such as financial limitations or insurance coverage, or lack of availability of dialysis services. Current guidelines recommend that twice weekly dialysis be performed in patients with kidney urea clearance greater than 3ml/min/1.73m2 or a urine output over 0.5 liter per day.

A systemic review and meta-analysis showed no difference in mortality, hospitalization rates, or quality of life between patients receiving incremental and conventional HD, with improved preservation of residual renal function and a reduction in dialysis cost with incremental HD. One randomized controlled trial (RCT) showed no difference in episodes of fluid overload or hyperkalemia, but an increased risk of hyperkalemia with incremental HD. Another study showed lower hospitalization rate in incremental HD compared to conventional dialysis. These studies demonstrate the need for a large RCT comparing incremental and conventional HD.

However, current studies do not provide conclusive evidence on the benefits and risks of incremental HD in elderly patients. Therefore, the investigators are conducting a pragmatic RCT to determine whether the initiation of renal replacement therapy with twice-weekly HD reduces hospitalization rates compared to conventional thrice-weekly HD in older adults with ESKD.

Trial design PRIDE trial is designed as a pragmatic RCT comparing the effect of initiating twice-weekly hemodialysis with an incremental approach compared to thrice-weekly HD on hospitalization rates in elderly ESKD patients with RKF. A total of 428 participants will be recruited from 18 academic dialysis centers in Korea. Participants will have the flexibility to transfer to other dialysis centers as needed. The decision to increase dialysis frequency will be made by the treating physicians.

Hypothesis Our main hypothesis is that twice-weekly HD, when prescribed to older adults with RKF will reduce hospitalization rates compared with thrice-weekly HD.

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2. Hong YA, Ban TH, Kang CY, et al. Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS). Kidney Res Clin Pract 2021;40:52-61.
3. Choi HS, Han KD, Oh TR, et al. Trends in the incidence and prevalence of end-stage renal disease with hemodialysis in entire Korean population: A nationwide population-based study. Medicine (Baltimore) 2021;100:e25293.
4. Verberne WR, Geers AB, Jellema WT, Vincent HH, van Delden JJ, Bos WJ. Comparative Survival among Older Adults with Advanced Kidney Disease Managed Conservatively Versus with Dialysis. Clin J Am Soc Nephrol 2016;11:633-640.
5. Corbett RW, Brown EA. Conventional dialysis in the elderly: How lenient should our guidelines be? Semin Dial 2018;31:607-611.
6. Bieber B, Qian J, Anand S, et al. Two-times weekly hemodialysis in China: frequency, associated patient and treatment characteristics and Quality of Life in the China Dialysis Outcomes and Practice Patterns study. Nephrol Dial Transplant 2014;29:1770-1777.
7. Santos J, Oliveira P, Malheiro J, et al. Predicting 6-Month Mortality in Incident Elderly Dialysis Patients: A Simple Prognostic Score. Kidney Blood Press Res 2020;45:38-50.
8. Yazawa M, Kido R, Ohira S, et al. Early Mortality Was Highly and Strongly Associated with Functional Status in Incident Japanese Hemodialysis Patients: A Cohort Study of the Large National Dialysis Registry. PLoS One 2016;11:e0156951.
9. Buemi M, Lacquaniti A, Bolignano D, et al. Dialysis and the elderly: an underestimated problem. Kidney Blood Press Res 2008;31:330-336.
10. Wang HH, Wu JL, Lee YC, et al. Risk of Serious Falls Between Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-based Cohort Study. Sci Rep 2020;10:7799.
11. Caton E, Sharma S, Vilar E, Farrington K. Impact of incremental initiation of haemodialysis on mortality: a systematic review and meta-analysis. Nephrol Dial Transplant 2023;38:435-446.
12. Hemodialysis Adequacy Work G. Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006;48 Suppl 1:S2-90.
13. Kalantar-Zadeh K, Unruh M, Zager PG, et al. Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy. Am J Kidney Dis 2014;64:181-186.
14. Vilar E, Kaja Kamal RM, Fotheringham J, et al. A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function. Kidney Int 2022;101:615-625.
15. Murea M, Patel A, Highland BR, et al. Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. Am J Kidney Dis 2022;80:227-240 e221.

• Study Type: Interventional
• Enrollment (Estimated): 428
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Soon Hyo Kwon, MD; Phone Number: +8227099177; Email: ksoonhyo@schmc.ac.kr
• Study Contact Backup: Name: Sook Kim; Phone Number: +8227099177; Email: himoomin@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 04401
    • Recruiting
    • SoonChunHyang University Seoul Hospital
    • Contact: Soon Hyo Kwon, MD; Phone Number: +8227099177; Email: ksoonhyo@schmc.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥60 years
• Clinical diagnosis of end stage kidney disease
• Starting maintenance hemodialysis within one month
• 24-hour urine output ≥ 500 ml at randomization
• Sufficient understanding of the study procedures and requirements.

Exclusion Criteria:

• Left ventricular ejection fraction < 40%)
• Liver cirrhosis
• Current treatment for an active malignancy or active infection
• Onability or refusal to provide written informed consent
• enrollment in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Twice-weekly hemodialysis with incremental approach	Other: Hemodialysis; Number of weekly hemodialysis treatment
No Intervention: Thrice-weekly hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization rate	The total number of hospitalizations per 100 person-years	Follow up: 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dialysis related hospitalization rate	The total number of dialysis hospitalizations per 100 person-years	Follow up: 2 years
Length of Hospital Stay	per 1000 person-days	Follow up: 2 years
Complication of dialysis	Any complication of dialysis associated	Follow up: 2 years
Mortality rate	Any cause of death	Follow up: 2 years
The Clinical Frailty Scale	One item, minimum point: 1, maximum point: 9, High scores means worse outcome	Follow up: 2 years
Cost effective	Incremental Cost-Effectiveness Ratio, Higher scores means better	Follow up: 2 years
Kidney Disease Quality of Life Instrument (KDQOL)	24 items, minimum point 1, maximum point 5, high score means worse outcomes	Follow up: 2 years

Collaborators and Investigators

• Sponsor: Soonchunhyang University Hospital
• Collaborators: Ministry of Health & Welfare, Korea
• Investigators: Principal Investigator: Soon Hyo Kwon, MD, Soonchunhyang University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: October 7, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: HC21C0059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No