The Impact of Intraoperative Diuretic Use on Delayed Graft Function Following Deceased Donor Renal Transplantation

NCT07726134 | Not Yet Recruiting

• 2 other identifiers: 16816AHSC AFP Innovation Fund
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Delayed graft function, defined as the need for dialysis within seven days of kidney transplantation, is a common complication affecting deceased-donor kidney transplant recipients. It is associated with prolonged hospitalization, increased healthcare costs, higher rates of acute rejection, and poorer long-term graft survival. Intraoperative diuretics are routinely administered during kidney transplant surgery to promote early urine output and protect the kidney from injury during reperfusion. The two most commonly used agents are furosemide and mannitol. Despite decades of clinical use, no prospective randomized trial has directly compared these two medications, and practice remains highly variable across centres and individual surgeons. This single-centre, prospective, randomized, surgeon-blinded pilot trial will enroll 240 deceased-donor kidney transplant recipients at London Health Sciences Centre. Participants will be randomized in a 1:1 ratio, stratified by donor type, to receive either intraoperative furosemide or intraoperative mannitol. The primary feasibility outcomes include recruitment rate. The primary clinical outcome is the incidence of delayed graft function. Secondary outcomes include serum creatinine trajectory, urine output, dialysis requirements, perioperative complications, length of stay, and one-year graft and patient survival. This pilot trial will provide feasibility data and effect-size estimates necessary to inform the design of a future definitive multicentre randomized controlled trial.

Conditions

Delayed Graft Function; Kidney Transplantation

Keywords

Furosemide; Lasix; Mannitol; Intraoperative diuretics; Kidney transplantation; Renal transplantation; Deceased donor kidney transplantation; Delayed graft function; DGF; Early graft function; Ischemia-reperfusion injury; Kidney allograft

Outcome Measures

Primary Outcomes (5)

• Recruitment rate

  Proportion of eligible patients who were approached and consented to enroll. Recruitment rate = number enrolled ÷ number of eligible patients screened. Reported as a percentage.

  From enrollment to the end of the study (1 year)

• Consent Rate

  Consent rate = number who consented ÷ number approached. Reported as a percentage.

  From enrollment to the end of the study (1 year).

• Protocol Adherence

  Proportion of study drug administrations (Lasix or Mannitol) delivered in accordance with the protocol, defined as correct dose given within the protocol specified time window.

  From enrollment to end of study (1 year)

• Data Completeness

  Proportion of expected data points that were successfully collected for the key outcome variables (e.g., DGF status, serum creatinine, urine output, and other pre-specified outcomes). Calculated as the number of data points collected ÷ number of data points expected per protocol, across all enrolled participants. Reported as a percentage.

  From enrollment to end of study (1 year)

• Delayed Graft Function (DGF)

  Defined as the requirement for at least one session of dialysis within the first seven days following kidney transplantation. This is a dichotomous outcome assessed at day 7 post-transplant (yes/no).

  From the administration of study drug until the end of post-op day 7.

Secondary Outcomes (4)

• Early graft function

  From the time of enrollment up until post op day 7.

• Postoperative dialysis requirement

  Post-op day 0 until the end of enrollment (1 year)

• Post-operative Outcomes

  Post-op day 0 until the end of post-op day 30

• Survival

  Post-op day 0 up until post-op day 365 (1 year post enrollment)

Study Arms (2)

Furosemide

ACTIVE COMPARATOR

In the Furosemide arm, 80 mg IV will be administered at 10-15 minutes prior to reperfusion of the transplanted kidney.

Drug: Furosemide

Mannitol

ACTIVE COMPARATOR

In the Mannitol arm, mannitol 0.5 g/kg IV will be administered at 10-15 minutes prior to reperfusion of the transplanted kidney.

Drug: Mannitol

Interventions

Furosemide DRUG

Furosemide is a potent loop diuretic that inhibits the sodium-potassium-2-chloride (Na+/K+/2Cl-) co-transporter (NKCC2) on the luminal surface of the thick ascending limb of the loop of Henle. By blocking this transporter, furosemide reduces sodium reabsorption, increases sodium and water delivery to the distal nephron, and produces a brisk natriuresis and diuresis. In participants randomized to the Furosemide arm, 80 mg IV will be administered at 10-15 minutes prior to reperfusion of the transplanted kidney.

Furosemide

Mannitol DRUG

Mannitol is a six-carbon sugar alcohol that is metabolically inert, freely filtered by the glomerulus, and largely unabsorbed by the renal tubules. It remains confined to the extracellular space and is excreted unchanged in the urine. As an osmotic diuretic, mannitol increases the osmolality of the glomerular filtrate, which opposes water reabsorption along the length of the nephron and produces dilute urine. In patients randomized to the Mannitol arm, mannitol 0.5 g/kg IV will be administered at 10-15 minutes prior to reperfusion of the transplanted kidney.

Mannitol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years;
• Patient is scheduled to receive a deceased-donor kidney transplant (including both NDD and DCD donors)
• Patient is willing and able to provide written and informed consent, or a substitute decision maker (SDM) is available to sign on the patient's behalf

You may not qualify if:

• Patient is receiving another organ at the time of their kidney transplant (e.g., simultaneous kidney-pancreas or kidney-liver)
• Known allergy or contraindication to mannitol or furosemide
• Inability to provide informed consent
• Pediatric recipients (\<18 years of age)
• Previously enrolled in this clinical trial

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Health Sciences Centre

London, Ontario, n6a 5a5, Canada

Location

Related Publications (24)

• Levine MA, Luke PP, Sener A. Canadian survey on the rates of use of intraoperative diuretics and justification for their use during renal allograft reperfusion. Can J Surg. 2020 Sep-Oct;63(5):E483-E488. doi: 10.1503/cjs.016019.

  PMID: 33107815 BACKGROUND

• Reiterer C, Hu K, Sljivic S, Falkner von Sonnenburg M, Fleischmann E, Kabon B. The effect of mannitol on oxidation-reduction potential in patients undergoing deceased donor renal transplantation-A randomized controlled trial. Acta Anaesthesiol Scand. 2021 Feb;65(2):162-168. doi: 10.1111/aas.13713. Epub 2020 Oct 15.

  PMID: 32966587 BACKGROUND

• van Valenberg PL, Hoitsma AJ, Tiggeler RG, Berden JH, van Lier HJ, Koene RA. Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation. Transplantation. 1987 Dec;44(6):784-8. doi: 10.1097/00007890-198712000-00012.

  PMID: 3122381 BACKGROUND

• Bipat R, Steels P, Cuypers Y, Toelsie JR. Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function. Nephron Extra. 2011 Jan;1(1):201-11. doi: 10.1159/000333478. Epub 2011 Nov 4.

  PMID: 22470393 BACKGROUND

• Waskowski J, Pfortmueller CA, Erdoes G, Buehlmann R, Messmer AS, Luedi MM, Schmidli J, Schefold JC. Mannitol for the Prevention of Peri-Operative Acute Kidney Injury: A Systematic Review. Eur J Vasc Endovasc Surg. 2019 Jul;58(1):130-140. doi: 10.1016/j.ejvs.2019.02.003. Epub 2019 May 9.

  PMID: 31078413 BACKGROUND

• Schnuelle P, Johannes van der Woude F. Perioperative fluid management in renal transplantation: a narrative review of the literature. Transpl Int. 2006 Dec;19(12):947-59. doi: 10.1111/j.1432-2277.2006.00356.x.

  PMID: 17081224 BACKGROUND

• McMahon BA, Koyner JL, Novick T, Menez S, Moran RA, Lonze BE, Desai N, Alasfar S, Borja M, Merritt WT, Ariyo P, Chawla LS, Kraus E. The prognostic value of the furosemide stress test in predicting delayed graft function following deceased donor kidney transplantation. Biomarkers. 2018 Feb;23(1):61-69. doi: 10.1080/1354750X.2017.1387934. Epub 2017 Oct 16.

  PMID: 29034718 BACKGROUND

• Sandal S, Bansal P, Cantarovich M. The evidence and rationale for the perioperative use of loop diuretics during kidney transplantation: A comprehensive review. Transplant Rev (Orlando). 2018 Apr;32(2):92-101. doi: 10.1016/j.trre.2017.11.002. Epub 2017 Nov 23.

  PMID: 29242033 BACKGROUND

• Tiggeler RG, Berden JH, Hoitsma AJ, Koene RA. Prevention of acute tubular necrosis in cadaveric kidney transplantation by the combined use of mannitol and moderate hydration. Ann Surg. 1985 Feb;201(2):246-51. doi: 10.1097/00000658-198502000-00020.

  PMID: 3918517 BACKGROUND

• Iguchi N, Lankadeva YR, Mori TA, Osawa EA, Cutuli SL, Evans RG, Bellomo R, May CN. Furosemide reverses medullary tissue hypoxia in ovine septic acute kidney injury. Am J Physiol Regul Integr Comp Physiol. 2019 Aug 1;317(2):R232-R239. doi: 10.1152/ajpregu.00371.2018. Epub 2019 May 29.

  PMID: 31141418 BACKGROUND

• Kim DW, Tsapepas D, King KL, Husain SA, Corvino FA, Dillon A, Wang W, Mayne TJ, Mohan S. Financial impact of delayed graft function in kidney transplantation. Clin Transplant. 2020 Oct;34(10):e14022. doi: 10.1111/ctr.14022. Epub 2020 Aug 11.

  PMID: 32573812 BACKGROUND

• Wu WK, Famure O, Li Y, Kim SJ. Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney Int. 2015 Oct;88(4):851-8. doi: 10.1038/ki.2015.190. Epub 2015 Jun 24.

  PMID: 26108067 BACKGROUND

• Zhao H, Alam A, Soo AP, George AJT, Ma D. Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond. EBioMedicine. 2018 Feb;28:31-42. doi: 10.1016/j.ebiom.2018.01.025. Epub 2018 Feb 2.

  PMID: 29398595 BACKGROUND

• Irish WD, Ilsley JN, Schnitzler MA, Feng S, Brennan DC. A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant. 2010 Oct;10(10):2279-86. doi: 10.1111/j.1600-6143.2010.03179.x.

  PMID: 20883559 BACKGROUND

• Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988 Apr;45(4):673-6. doi: 10.1097/00007890-198804000-00001. No abstract available.

  PMID: 3282347 BACKGROUND

• Laar SCV, Schouten GN, IJzermans JNM, Minnee RC. Effect of Mannitol on Kidney Function After Kidney Transplantation: A Systematic Review and Meta-Analysis. Transplant Proc. 2021 Sep;53(7):2122-2132. doi: 10.1016/j.transproceed.2021.07.001. Epub 2021 Aug 16.

  PMID: 34412911 BACKGROUND

• Snoeijs MG, Winkens B, Heemskerk MB, Hoitsma AJ, Christiaans MH, Buurman WA, van Heurn LW. Kidney transplantation from donors after cardiac death: a 25-year experience. Transplantation. 2010 Nov 27;90(10):1106-12. doi: 10.1097/TP.0b013e3181f83b0b.

  PMID: 20861804 BACKGROUND

• Thuillier R, Favreau F, Celhay O, Macchi L, Milin S, Hauet T. Thrombin inhibition during kidney ischemia-reperfusion reduces chronic graft inflammation and tubular atrophy. Transplantation. 2010 Sep 27;90(6):612-21. doi: 10.1097/tp.0b013e3181d72117.

  PMID: 20865816 BACKGROUND

• Koo DD, Welsh KI, Roake JA, Morris PJ, Fuggle SV. Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion. Am J Pathol. 1998 Aug;153(2):557-66. doi: 10.1016/S0002-9440(10)65598-8.

  PMID: 9708815 BACKGROUND

• Levine MA, Rasmussen A, Lee D, Rim C, Farokhi K, Luke PP, Sener A. Prospective assessment of the impact of intraoperative diuretics in kidney transplant recipient surgery. Can J Surg. 2024 Apr 4;67(2):E158-E164. doi: 10.1503/cjs.006422. Print 2024 Jan-Feb.

  PMID: 38575180 BACKGROUND

• Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004 Nov 13-19;364(9447):1814-27. doi: 10.1016/S0140-6736(04)17406-0.

  PMID: 15541456 BACKGROUND

• Yarlagadda SG, Coca SG, Formica RN Jr, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant. 2009 Mar;24(3):1039-47. doi: 10.1093/ndt/gfn667. Epub 2008 Dec 22.

  PMID: 19103734 BACKGROUND

• Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011 Nov;11(11):2279-96. doi: 10.1111/j.1600-6143.2011.03754.x. Epub 2011 Sep 19.

  PMID: 21929642 BACKGROUND

• Levine MA, Chin JL, Rasmussen A, Sener A, Luke PP. The history of renal transplantation in Canada: A urologic perspective. Can Urol Assoc J. 2020 Dec;14(12):372-379. doi: 10.5489/cuaj.6744.

  PMID: 32569569 BACKGROUND

MeSH Terms

Conditions

Delayed Graft Function; Reperfusion Injury

Interventions

Furosemide; Mannitol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Sugar Alcohols; Alcohols; Carbohydrates

Central Study Contacts

Cadence Research Manager, BSc, MSc

CONTACT

(519) 685-8500; Cadence.Baker@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 24, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 24, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)