IPUF-HD: Interdialytic Peritoneal UltraFiltration in HemoDialysis Patients
Study Details
Study Description
Brief Summary
Sodium accumulates in the tissues of patients with kidney disease and impairs survival. Three-times weekly, standard hemodialysis alone cannot remove excess sodium efficiently. A sample of 10 chronic hemodialysis patients will undergo a 5-week, pilot, interventional study to test the efficacy of additional sodium removal in-between hemodialysis sessions, twice per week, for three weeks. Tissue sodium removal will be achieved with peritoneal dialysis after the surgical insertion of a peritoneal dialysis catheter. Tissue sodium removal will be assessed at the beginning and at the end of the study with sodium magnetic resonance imaging of a peripheral limb (leg). Patients will also undergo monitoring for symptoms and blood pressure throughout the study to assess the safety of this procedure.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Hypothesis: Interdialytic peritoneal ultrafiltration (iPUF) via Tenckhoff peritoneal dialysis catheter using 10% Dextrose infusate is feasible and provides effective volume management and sodium removal in prevalent HD patients.
Overview: This is a prospective, interventional pilot study from the London Health Sciences Centre (LHSC) prevalent HD population. Study patients will undergo the surgical implantation of a Tenckhoff peritoneal dialysis catheter before study start. After the successful insertion of the Tenckhoff catheter, study patients will enter a run-in phase, where their residual renal function, volume, hemodynamic and cardiac status during HD will be assessed. During the following weeks (intervention weeks 1, 2, 3), study patients will receive in-center iPUF intervention, consisting of peritoneal infusate instillation of a 10% dextrose solution via a Tenckhoff catheter, immediately after the first two HD sessions of the week (Monday, Wednesday); the infusate will be dwelling in the study patient's peritoneal cavity for 2 hours, at the end of which the solution will be drained and the patient sent home. Study patients will be monitored during infusate administration and for the first four hours thereafter. The study intervention will be discontinued at the beginning of week 5 (Wash-out); during week 5 and the first HD session of week 6, study patients will be monitored to observe potential residual effects of the iPUF intervention.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Interdialytic peritoneal ultrafiltration Will receive incremental interdialytic peritoneal ultrafiltration with a 10% dextrose solution, twice a week for three consecutive weeks |
Combination Product: Interdialytic peritoneal ultrafiltration with 10% dextrose solution
Interdialytic peritoneal ultrafiltration with incremental doses of a 10% dextrose solution, after hemodialysis twice weekly for three consecutive weeks
|
Outcome Measures
Primary Outcome Measures
- Skin sodium concentration [End of week 4]
Skin sodium concentration at the end of week 4 as measured by sodium-23 magnetic resonance imaging of the leg.
- Adverse events [iPUF interventions on Week 2, 3 and 4]
Completion of the iPUF treatment without adverse events
Secondary Outcome Measures
- Interdialytic weight gain [week 1 vs 4, week 1 vs 5-6]
Difference in interdialytic weight gain at run-in week vs end of intervention, vs wash-out
- Total weekly sodium removal with interdialytic peritoneal ultrafiltration [week 2, 3, 4]
Total weekly sodium removal with peritoneal dialysis in intervention weeks
- Total volume of fluid removed with interdialytic peritoneal ultrafiltration [week 2, 3, 4]
Total volume of fluid removed with peritoneal dialysis in intervention weeks
- Home blood pressure [week 1 vs week 4, week 1 vs 5-6]
Changes in home blood pressure at baseline vs end of intervention and vs washout
- Mean intradialytic hemodynamics [week 1 vs 4, week 1 vs 6]
Changes in mean intradialytic hemodynamic monitor parameters, as measured with Finometer and CVInsight
- Regional wall motion abnormalities [week 1 vs 4, week 1 vs 6]
Changes in Regional Wall Motion Abnormalities (echocardiography) at peak-stress hemodialysis
- Symptoms [week 1 vs 4, week 1 vs 6]
Changes in symptoms as measured with the London Evaluation of Illness questionnaire
- Infusion pain [Through study completion, average of all study treatments]
Infusion pain as measured with 0-10 visual analog scale
- Changes in serum sodium [Through study completion, average of all study treatments]
Post-iPUF change in serum sodium
Eligibility Criteria
Criteria
Inclusion Criteria
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At least one of the following:
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Average per-session interdialytic weight gain ≥ 4.0 % of their dry weight in the last month;
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Inability to consistently achieve dry weight with the current treatment schedule;
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Need for additional HD treatments to achieve prescribed dry weight.
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Weekly HD sessions - up to three times/week
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Age ≥18 years
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Willing and able to give informed consent
Exclusion Criteria
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Contraindications to peritoneal dialysis
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Contraindications to MRI
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Uncontrolled diabetes mellitus
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Active infections
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Non-compliance to hemodialysis prescription
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Pre-study serum sodium < 130 mmol/L
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | London Health Sciences Centre | London | Ontario | Canada | N6A 5W9 |
Sponsors and Collaborators
- Lawson Health Research Institute
- Sequana Medical N.V.
Investigators
- Principal Investigator: Christopher W. McIntyre, MD, PhD, Lawson Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
- Assimon MM, Wang L, Flythe JE. Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis. J Am Soc Nephrol. 2018 Aug;29(8):2178-2188. doi: 10.1681/ASN.2018010004. Epub 2018 May 23.
- Banshodani M, Kawanishi H, Moriishi M, Shintaku S, Tsuchiya S. Association between Dialysis Modality and Cardiovascular Diseases: A Comparison between Peritoneal Dialysis and Hemodialysis. Blood Purif. 2020;49(3):302-309. doi: 10.1159/000504040. Epub 2019 Dec 18.
- Canaud B, Kooman J, Selby NM, Taal M, Francis S, Kopperschmidt P, Maierhofer A, Kotanko P, Titze J. Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease. Kidney Int. 2019 Feb;95(2):296-309. doi: 10.1016/j.kint.2018.09.024. Review.
- Dahlmann A, Dörfelt K, Eicher F, Linz P, Kopp C, Mössinger I, Horn S, Büschges-Seraphin B, Wabel P, Hammon M, Cavallaro A, Eckardt KU, Kotanko P, Levin NW, Johannes B, Uder M, Luft FC, Müller DN, Titze JM. Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients. Kidney Int. 2015 Feb;87(2):434-41. doi: 10.1038/ki.2014.269. Epub 2014 Aug 6.
- Flythe JE, Curhan GC, Brunelli SM. Disentangling the ultrafiltration rate-mortality association: the respective roles of session length and weight gain. Clin J Am Soc Nephrol. 2013 Jul;8(7):1151-61. doi: 10.2215/CJN.09460912. Epub 2013 Mar 14.
- Grieff M, Mamo E, Scroggins G, Kurchin A. The 'Pull' Technique for Removal of Peritoneal Dialysis Catheters: A Call for Re-Evaluation of Practice Standards. Perit Dial Int. 2017 Mar-Apr;37(2):225-229. doi: 10.3747/pdi.2016.00152.
- Kanda R, Io H, Nakata J, Makita Y, Sasaki Y, Matsumoto M, Wakabayashi K, Tomino Y, Suzuki Y. Evaluation of Long-Term Combination Therapy With Peritoneal Dialysis and Hemodialysis. Ther Apher Dial. 2017 Apr;21(2):180-184. doi: 10.1111/1744-9987.12517. Epub 2017 Feb 10.
- Kawanishi H, Hashimoto Y, Nakamoto H, Nakayama M, Tranaeus A. Combination therapy with peritoneal dialysis and hemodialysis. Perit Dial Int. 2006 Mar-Apr;26(2):150-4.
- Kopp C, Linz P, Wachsmuth L, Dahlmann A, Horbach T, Schöfl C, Renz W, Santoro D, Niendorf T, Müller DN, Neininger M, Cavallaro A, Eckardt KU, Schmieder RE, Luft FC, Uder M, Titze J. (23)Na magnetic resonance imaging of tissue sodium. Hypertension. 2012 Jan;59(1):167-72. doi: 10.1161/HYPERTENSIONAHA.111.183517. Epub 2011 Dec 5.
- Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Müller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009 May;15(5):545-52. doi: 10.1038/nm.1960. Epub 2009 May 3.
- McIntyre CW. Bimodal dialysis: an integrated approach to renal replacement therapy. Perit Dial Int. 2004 Nov-Dec;24(6):547-53.
- Obi Y, Rhee CM, Mathew AT, Shah G, Streja E, Brunelli SM, Kovesdy CP, Mehrotra R, Kalantar-Zadeh K. Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients. J Am Soc Nephrol. 2016 Dec;27(12):3758-3768. Epub 2016 May 11.
- Qirjazi E, Salerno FR, Akbari A, Hur L, Penny J, Scholl T, McIntyre CW. Tissue sodium concentrations in chronic kidney disease and dialysis patients by lower leg sodium-23 magnetic resonance imaging. Nephrol Dial Transplant. 2020 Apr 6. pii: gfaa036. doi: 10.1093/ndt/gfaa036. [Epub ahead of print]
- Quiroga I, Reddy SP, Bhattacharjya S, Darby CR. Tenckhoff catheters: the pull technique. Nephrol Dial Transplant. 2003 Aug;18(8):1682.
- Quiroga IM, Baboo R, Lord RH, Darby CR. Tenckhoff catheters post-renal transplantation: the 'pull' technique? Nephrol Dial Transplant. 2001 Oct;16(10):2079-81.
- Ramdeen G, Tzamaloukas AH, Malhotra D, Leger A, Murata GH. Estimates of interdialytic sodium and water intake based on the balance principle: differences between nondiabetic and diabetic subjects on hemodialysis. ASAIO J. 1998 Nov-Dec;44(6):812-7.
- Rao VS, Turner JM, Griffin M, Mahoney D, Asher J, Jeon S, Yoo PS, Boutagy N, Feher A, Sinusas A, Wilson FP, Finkelstein F, Testani JM. First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution: A New Candidate Therapy for Volume Overload. Circulation. 2020 Mar 31;141(13):1043-1053. doi: 10.1161/CIRCULATIONAHA.119.043062. Epub 2020 Jan 8.
- Santos SF, Peixoto AJ. Sodium balance in maintenance hemodialysis. Semin Dial. 2010 Nov-Dec;23(6):549-55. doi: 10.1111/j.1525-139X.2010.00794.x. Review.
- Sriperumbuduri S, Biyani M, Brown PA, McCormick BB. Retrospective study of patients on hybrid dialysis: Single-center data from North America. Perit Dial Int. 2020 Mar;40(2):224-226. doi: 10.1177/0896860819887284. Epub 2020 Jan 17.
- Titze J, Lang R, Ilies C, Schwind KH, Kirsch KA, Dietsch P, Luft FC, Hilgers KF. Osmotically inactive skin Na+ storage in rats. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1108-17. Epub 2003 Jul 29.
- Wenstedt EFE, Olde Engberink RHG, Vogt L. Sodium Handling by the Blood Vessel Wall: Critical for Hypertension Development. Hypertension. 2018 Jun;71(6):990-996. doi: 10.1161/HYPERTENSIONAHA.118.10211. Epub 2018 Apr 16. Review.
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