Impact of incremental versus conventional initiation of haemodialysis on residual kidney function: study protocol for a multicentre feasibility randomised controlled trial

Raja Mohammed Kaja Kamal, Ken Farrington, David Wellsted, Sivakumar Sridharan, Bassam Alchi, James Burton, Andrew Davenport, Enric Vilar, Raja Mohammed Kaja Kamal, Ken Farrington, David Wellsted, Sivakumar Sridharan, Bassam Alchi, James Burton, Andrew Davenport, Enric Vilar

Abstract

Introduction: Preserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve RKF. In Incremental HD, target dose includes a contribution from RKF, which is added to HD dose, allowing individualisation of the HD prescription. We will conduct a feasibility randomised controlled trial (RCT) comparing incremental HD and conventional three times weekly treatments in incident HD patients. The study is designed also to provide pilot data to allow determination of effect size to power a definitive study.

Methods and analysis: After screening to ensure native renal urea clearance >3 mL/min/1.73 m2, the study will randomise 54 patients within 3 months of HD initiation to conventional in-centre thrice weekly dialysis or incremental in-centre HD commencing 2 days a week. Subjects will be followed up for 12 months. The study will be carried out across four UK renal centres.The primary outcome is to evaluate the feasibility of conducting a definitive RCT and to estimate the difference in rate of decline of RKF between the two groups at 6 and 12 months time points. Secondary outcomes will include the impact of dialysis intensity on vascular access events, major adverse cardiac events and survival. Impact of dialysis intensity on patient-reported outcomes measures, cognition and frailty will be assessed using EQ-5D-5L, PHQ-9, Illness Intrusiveness Rating Score, Montreal Cognitive assessment and Clinical Frailty Score. Safety outcomes include hospitalisation, fluid overload episodes, hyperkalaemia events and vascular access events.This study will inform the design of a definitive study, adequately powered to determine whether RKF is better preserved after incremental HD initiation compared with conventional initiation.

Ethics and dissemination: Ethics approval has been granted by Cambridge South Research Ethics Committee, United Kingdom(REC17/EE/0311). Results will be disseminated via peer-reviewed publication.

Trial registration number: NCT03418181.

Keywords: adult nephrology; dialysis; end stage renal failure.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow diagram of clinical trial demonstrating data that will be used to calculate eligibility for screening, screen failure rate, recruitability and retainability. HD, haemodialysis; RKF, residual kidney function; Std Kt/V, Standard Kt/V.
Figure 2
Figure 2
Timing of urine collection and blood tests for dialysis adequacy measurement for patients on twice Weekly and thrice weekly HD. HD, haemodialysis.

References

    1. 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;64:181–6. 10.1053/j.ajkd.2014.04.019
    1. Davenport A. Will incremental hemodialysis preserve residual function and improve patient survival? Semin Dial 2015;28:16–19. 10.1111/sdi.12320
    1. Wong J, Vilar E, Davenport A, et al. . Incremental haemodialysis. Nephrol Dial Transplant 2015;30:1639–48. 10.1093/ndt/gfv231
    1. Gilmore J. KDOQI clinical practice guidelines and clinical practice recommendations--2006 updates. Nephrol Nurs J 2006;33:487–8.
    1. Hanson JA, Hulbert-Shearon TE, Ojo AO, et al. . Prescription of twice-weekly hemodialysis in the USA. Am J Nephrol 1999;19:625–33. 10.1159/000013533
    1. Lin Y-F, Huang J-W, Wu M-S, et al. . Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology 2009;14:59–64. 10.1111/j.1440-1797.2008.01016.x
    1. Vilar E, Wellsted D, Chandna SM, et al. . Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose. Nephrol Dial Transplant 2009;24:2502–10. 10.1093/ndt/gfp071
    1. Supasyndh O, Satirapoj B, Seenamngoen S, et al. . Nutritional status of twice and thrice-weekly hemodialysis patients with weekly Kt/V > 3.6. J Med Assoc Thai 2009;92:624–31.
    1. Lin X, Yan Y, Ni Z, et al. . Clinical outcome of twice-weekly hemodialysis patients in Shanghai. Blood Purif 2012;33:66–72. 10.1159/000334634
    1. Milagros Fernandez Lucas JLT, Ruiz-Roso G, Diaz M, et al. . Incremental hemodialysis schedule in patients with higher residual renal function at the start of dialysis. Advances in Nephrology 2014:6.
    1. Zhang M, Wang M, Li H, et al. . Association of initial twice-weekly hemodialysis treatment with preservation of residual kidney function in ESRD patients. Am J Nephrol 2014;40:140–50. 10.1159/000365819
    1. 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;29:1770–7. 10.1093/ndt/gft472
    1. Elamin S, Abu-Aisha H. Reaching target hemoglobin level and having a functioning arteriovenous fistula significantly improve one year survival in twice Weekly hemodialysis. Arab J Nephrol Transplant 2012;5:81–6.
    1. Cheng Y, Tu W, Xiao Q, et al. . Risk of cardiovascular disease in patients on thrice-weekly versus twice-weekly hemodialysis. Int J Cardiol 2014;174:780–3. 10.1016/j.ijcard.2014.04.052
    1. Lei G, Li X, Tu W, et al. . Risk of intradialytic hypotension in patients on thrice-weekly versus twice-weekly hemodialysis. Int J Cardiol 2014;174:821–3. 10.1016/j.ijcard.2014.04.140
    1. Panaput T, Thinkhamrop B, Domrongkitchaiporn S, et al. . Dialysis dose and risk factors for death among ESRD patients treated with twice-weekly hemodialysis: a prospective cohort study. Blood Purif 2014;38:253–62. 10.1159/000368885
    1. Obi Y, Streja E, Rhee CM, et al. . Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study. Am J Kidney Dis 2016;68:256–65. 10.1053/j.ajkd.2016.01.008
    1. Caria S, Cupisti A, Sau G, et al. . The incremental treatment of ESRD: a low-protein diet combined with Weekly hemodialysis may be beneficial for selected patients. BMC Nephrol 2014;15:172. 10.1186/1471-2369-15-172
    1. Fernández-Lucas M, Teruel-Briones JL, Gomis-Couto A, et al. . Maintaining residual renal function in patients on haemodialysis: 5-year experience using a progressively increasing dialysis regimen. Nefrologia 2012;32:767–76. 10.3265/Nefrologia.pre2012.Jul.11517
    1. Devins GM. Using the illness intrusiveness ratings scale to understand health-related quality of life in chronic disease. J Psychosom Res 2010;68:591–602. 10.1016/j.jpsychores.2009.05.006
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Nasreddine ZS, Phillips NA, Bédirian V, et al. . The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695–9. 10.1111/j.1532-5415.2005.53221.x
    1. Tiffin-Richards FE, Costa AS, Holschbach B, et al. . The Montreal Cognitive Assessment (MoCA) - a sensitive screening instrument for detecting cognitive impairment in chronic hemodialysis patients. PLoS One 2014;9:e106700. 10.1371/journal.pone.0106700
    1. Moorhouse P, Rockwood K. Frailty and its quantitative clinical evaluation. J R Coll Physicians Edinb 2012;42:333–40. 10.4997/JRCPE.2012.412
    1. Alfaadhel TA, Soroka SD, Kiberd BA, et al. . Frailty and mortality in dialysis: evaluation of a clinical frailty scale. Clin J Am Soc Nephrol 2015;10:832–40. 10.2215/CJN.07760814
    1. Gotch FA. The current place of urea kinetic modelling with respect to different dialysis modalities. Nephrol Dial Transplant 1998;13:10–14. 10.1093/ndt/13.suppl_6.10
    1. Casino FG, Lopez T. The equivalent renal urea clearance: a new parameter to assess dialysis dose. Nephrol Dial Transplant 1996;11:1574–81. 10.1093/oxfordjournals.ndt.a027616
    1. Kaja Kamal RM, Farrington K, Busby AD, et al. . Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function. Nephrol Dial Transplant 2019;34:1017–25. 10.1093/ndt/gfy321
    1. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat 2005;4:287–91. 10.1002/pst.185
    1. Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol 2012;65:301–8. 10.1016/j.jclinepi.2011.07.011
    1. Wong J, Sridharan S, Berdeprado J, et al. . Predicting residual kidney function in hemodialysis patients using serum β-trace protein and β2-microglobulin. Kidney Int 2016;89:1090–8. 10.1016/j.kint.2015.12.042
    1. Hemodialysis Adequacy 2006 Work Group Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006;48:S2–90. 10.1053/j.ajkd.2006.03.051

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