Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: a prospective randomized open-label clinical study protocol

Vaibhav Maheshwari, Lakshminarayanan Samavedham, Gade Pandu Rangaiah, Yijun Loy, Lieng Hsi Ling, Sunil Sethi, Titus Lau Wai Leong, Vaibhav Maheshwari, Lakshminarayanan Samavedham, Gade Pandu Rangaiah, Yijun Loy, Lieng Hsi Ling, Sunil Sethi, Titus Lau Wai Leong

Abstract

Background: Maintenance hemodialysis (HD) patients universally suffer from excess toxin load. Hemodiafiltration (HDF) has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF.

Methods/design: The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and β2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a) high flux HD, (b) post-dilution HDF, (c) high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters.

Discussion: This will be the first study to investigate the exercise induced physiological change(s) responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing, sustaining, and optimizing the exercise in routine dialysis care. We anticipate that toxin removal outcomes from intra-dialytic exercise session will be comparable to that obtained by standalone HDF. These results will encourage clinicians to combine HDF with intra-dialytic exercise for significantly enhanced toxin removal.

Trial registration: ClinicalTrials.gov number, NCT01674153.

Figures

Figure 1
Figure 1
Flow chart of the clinical trial.
Figure 2
Figure 2
Diffusion-adjusted regional blood flow model (parallel-cum-series representation of physiology) or explaining β2-microglobulin kinetics. Toxin transfer is due to diffusion across capillary endothelium, and blood/plasma circulation causes convective transport. Qh/Qhp, Ql/Qlp, and Qb/Qbp are blood/plasma flows to high flow region (HFR), low flow region (LFR), and dialyzer, respectively. Qcr and Qar are cardiopulmonary and access recirculation, respectively. Shaded compartments represent contact with blood (A – arterial node and V – venous node) [14].

References

    1. Parsons TL, Toffelmire EB, King-Van Vlack CE. Exercise training during hemodialysis improves dialysis efficacy and physical performance. Arch Phys Med Rehabil. 2006;87:680–687. doi: 10.1016/j.apmr.2005.12.044.
    1. U S Renal Data System, USRDS 2012 Annual Data Report. Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
    1. Krick G, Ronco C. On-line Hemodiafiltration: The Journey and the Vision. S Karger Ag. 2011.
    1. Schiffl H. Prospective randomized cross-over long-term comparison of online haemodiafiltration and ultrapure high-flux haemodialysis. Eur J Med Res. 2007;12:26–33.
    1. Ward RA, Schmidt B, Hullin J, Hillebrand GF, Samtleben W. A comparison of on-line hemodiafiltration and high-flux hemodialysis: A prospective clinical study. J Am Soc Nephrol. 2000;11:2344–2350.
    1. Pedrini LA, De Cristofaro V, Comelli M, Casino FG, Prencipe M, Baroni A, Campolo G, Manzoni C, Colì L, Ruggiero P. Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity, A multicentre prospective randomized study. Nephrol Dial Transplant. 2011;26:2617–2624. doi: 10.1093/ndt/gfq761.
    1. Wizemann V, Lotz C, Techert F, Uthoff S. Online haemodiafiltration versus low-flux haemodialysis, A prospective randomized study. Nephrol Dial Transplant. 2000;15:43–48.
    1. Maduell F, Arias M, Vera M, Fontseré N, Blasco M, Barros X, Garro J, Elena M, Bergadá E, Cases A. et al.Mid-dilution hemodiafiltration: A comparison with pre- and postdilution modes using the same polyphenylene membrane. Blood Purif. 2009;28:268–274. doi: 10.1159/000232935.
    1. Thomas G, Jaber BL. Convective therapies for removal of middle molecular weight uremic toxins in end-stage renal disease: a review of the evidence. Semin Dial. 2009;22:610–614. doi: 10.1111/j.1525-139X.2009.00665.x.
    1. Locatelli F, Manzoni C, Cavalli A, Di Filippo S. Can convective therapies improve dialysis outcomes? Curr Opin Nephrol Hypertens. 2009;18:476–480. doi: 10.1097/MNH.0b013e3283318e8b.
    1. Drueke TB. β2-Microglobulin and amyloidosis. Nephrol Dial Transplant. 2000;15:17–24. doi: 10.1093/oxfordjournals.ndt.a027958.
    1. Cheung AK, Rocco MV, Yan G, Leypoldt JK, Levin NW, Greene T, Agodoa L, Bailey J, Beck GJ, Clark W. Serum beta-2 microglobulin levels predict mortality in dialysis patients: Results of the HEMO study. J Am Soc Nephrol. 2006;17:546–555. doi: 10.1681/ASN.2005020132.
    1. Okuno S, Ishimura E, Kohno K, Fujino-Katoh Y, Maeno Y, Yamakawa T, Inaba M, Nishizawa Y. Serum beta2-microglobulin level is a significant predictor of mortality in maintenance haemodialysis patients. Nephrol Dial Transplant. 2009;24:571–577.
    1. Maheshwari V, Samavedham L, Rangaiah G. A Regional Blood Flow Model for β2-Microglobulin Kinetics and for Simulating Intra-dialytic Exercise Effect. Ann Biomed Eng. 2011;39:2879–2890. doi: 10.1007/s10439-011-0383-5.
    1. Ward RA, Greene T, Hartmann B, Samtleben W. Resistance to intercompartmental mass transfer limits beta(2)-microglobulin removal by post-dilution hemodiafiltration. Kidney Int. 2006;69:1431–1437.
    1. Stiller S, Xu XQ, Gruner N, Vienken J, Mann H. Validation of a two-pool model for the kinetics of Beta 2-microglobulin. Int J Artif Organs. 2002;25:411–420.
    1. Locatelli F. Comparison of Hemodialysis, Hemodiafiltration, and Hemofiltration: Systematic Review or Systematic Error? Am J Kidney Dis. 2005;46:787–788.
    1. Blankestijn PJ, Ledebo I, Canaud B. Hemodiafiltration: clinical evidence and remaining questions. Kidney Int. 2010;77:581–587. doi: 10.1038/ki.2009.541.
    1. Mucsi I, Hercz G, Uldall R, Ouwendyk M, Francoeur R, Pierratos A. Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis. Kidney Int. 1998;53:1399–1404. doi: 10.1046/j.1523-1755.1998.00875.x.
    1. Eloot S, van Biesen W, Dhondt A, de Smet R, Marescau B, De Deyn PP, Verdonck P, Vanholder R. Impact of increasing haemodialysis frequency versus haemodialysis duration on removal of urea and guanidino compounds: a kinetic analysis. Nephrol Dial Transplant. 2009;24:2225–2232. doi: 10.1093/ndt/gfp059.
    1. Kalousová M, Kielstein JT, Hodková M, Zima T, Dusilová-Sulková S, Martens-Lobenhoffer J, Bode-Boger SM. No Benefit of Hemodiafiltration over Hemodialysis in Lowering Elevated Levels of Asymmetric Dimethylarginine in ESRD Patients. Blood Purif. 2006;24:439–444. doi: 10.1159/000095360.
    1. Giannaki CD, Stefanidis I, Karatzaferi C, Liakos N, Roka V, Ntente I, Sakkas GK. The Effect of Prolonged Intradialytic Exercise in Hemodialysis Efficiency Indices. ASAIO J. 2011;57:213–218. doi: 10.1097/MAT.0b013e318215dc9e.
    1. Vaithilingam I, Polkinghorne KR, Atkins RC, Kerr PG. Time and exercise improve phosphate removal in hemodialysis patients. Am J Kidney Dis. 2004;43:85–89. doi: 10.1053/j.ajkd.2003.09.016.
    1. Kong CH, Tattersall JE, Greenwood RN, Farrington K. The effect of exercise during haemodialysis on solute removal. Nephrol Dial Transplant. 1999;14:2927–2931. doi: 10.1093/ndt/14.12.2927.
    1. Farese S, Budmiger R, Aregger F, Bergmann I, Frey F, Uehlinger D. Effect of transcutaneous electrical muscle stimulation and passive cycling movements on blood pressure and removal of urea and phosphate during hemodialysis. Am J Kidney Dis. 2008;52:745–752. doi: 10.1053/j.ajkd.2008.03.017.
    1. Schneditz D, Platzer D, Daugirdas JT. A diffusion-adjusted regional blood flow model to predict solute kinetics during haemodialysis. Nephrol Dial Transplant. 2009;24:2218–2224. doi: 10.1093/ndt/gfp023.
    1. Schneditz D, Van Stone JC, Daugirdas JT. A Regional blood circulation alternative to in-series two compartment urea kinetic modeling. ASAIO J. 1993;39:M573–M577.
    1. Smye S, Lindley E, Will E. Simulating the effect of exercise on urea clearance in hemodialysis. J Am Soc Nephrol. 1998;9:128–132.
    1. Vanholder R, Eloot S, Van Biesen W. Do we need new indicators of dialysis adequacy based on middle-molecule removal? Nat Clin Pract Nephrol. 2008;4:174–175. doi: 10.1038/ncpneph0750.
    1. Drüeke TB, Massy ZA. Progress in uremis toxin research: Beta2-microglobulin. Semin Dial. 2009;22:378–380. doi: 10.1111/j.1525-139X.2009.00584.x.
    1. Statement ATS. Guidelines for the Six-Minute Walk Test. Am J Respir Crit Care Med. 2002;166:111–117.
    1. Fitts SS, Guthrie MR. Six-minute walk by people with chronic renal failure: assessment of effort by perceived exertion. Am J Phys Med Rehabil. 1995;74:54. doi: 10.1097/00002060-199501000-00009.
    1. Yu A, Wong F, Rafiq M, Zhou F, Daugirdas J. Collection of a representative fraction of total spent hemodialysate. Am J Kidney Dis. 1995;25:810–812. doi: 10.1016/0272-6386(95)90560-X.
    1. Painter PL, Nelson-Worel JN, Hill M, Thornbery D, Shelp W, Harrington A, Weinstein A. Effects of exercise training during hemodialysis. Nephron. 1986;43:87–92. doi: 10.1159/000183805.
    1. Bennett PN, Breugelmans L, Barnard R, Agius M, Chan D, Fraser D, McNeill L, Potter L. Sustaining a hemodialysis exercise program: a review. Semin Dial. 2010;23:62–73. doi: 10.1111/j.1525-139X.2009.00652.x.
    1. Schneditz D. F1000 Recommendation of [Maheshwari V et al. Ann Biomed Eng. 2011;39(12):2879–2890. doi: 10.3410/f.13830964.15270068. Faculty of 1000, 27 Feb 2012. .

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