An interventional study of Furosemide and Mannitol in Delayed Graft Function and Kidney Transplantation, sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's. Recruiting at 2 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Not applicable, Interventional, and Treatment
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.
Kidney transplantation has been the treatment of choice for end-stage renal disease for over six decades, yet delayed graft function (DGF) remains one of the most common and clinically significant complications of deceased-donor kidney transplantation. Defined as the requirement for at least one session of dialysis within the first seven days following transplantation, DGF affects 20-40% of deceased-donor kidney transplant recipients depending on the donor population and centre. DGF is associated with prolonged hospitalization, increased healthcare costs, a 1.4- to 2-fold increase in acute rejection risk, and inferior long-term graft survival. The pathophysiology centres on ischemia-reperfusion injury (IRI), which causes acute tubular necrosis, endothelial dysfunction, microvascular thrombosis, and upregulation of allograft immunogenicity through increased expression of MHC molecules and damage-associated molecular patterns. Donor type significantly influences DGF risk: donation after circulatory death (DCD) organs carry the highest historic rates due to sustained hypoperfusion and anaerobic metabolism during the agonal phase, while donation after neurological death (NDD) organs are affected by systemic inflammatory responses driven by loss of sympathetic regulation. Intraoperative diuretics, furosemide and mannitol, have been used for decades during reperfusion to enhance early urine output and mitigate IRI. Furosemide, a loop diuretic, inhibits the NKCC2 co-transporter in the thick ascending limb, reducing tubular metabolic oxygen demand, promoting tubular flushing, and stimulating renal prostaglandin-mediated vasodilation. Mannitol, an osmotic diuretic, maintains high tubular flow rates, reduces tubular cell swelling, acts as a hydroxyl radical scavenger, and promotes intrarenal vasodilation through prostaglandin and natriuretic peptide release. Despite these plausible mechanisms, the evidence supporting either agent remains weak. A comprehensive review by Sandal et al. (2018) found that the evidence supporting loop diuretics in preventing DGF was poor, with no data on patient survival identified. Schnuelle and van der Woude similarly concluded that loop diuretics had not been shown to affect DGF rates or improve outcomes. For mannitol, while van Valenberg et al. described its intraoperative use as "indispensable" based on early trial data, and a systematic review by van de Laar et al. (2021) suggested lower rates of DGF with mannitol use, that review emphasized significant limitations in evidence quality and heterogeneity. A randomized trial by Reiterer et al. evaluating mannitol versus placebo in 34 deceased-donor recipients found no significant effect on oxidation-reduction potential. A preclinical study by Bipat et al. demonstrated that mannitol preserved diuresis and creatinine clearance in a rabbit model of hypoxic kidneys, providing mechanistic support but not clinical confirmation. Current clinical practice is highly heterogeneous. A UK survey of 40 transplant surgeons from 18 centres revealed that 13 used no intraoperative diuretics, 10 used mannitol alone, 6 used furosemide alone, and 11 used a combination, underscoring the complete lack of consensus. A Canadian survey similarly demonstrated wide variation in practice patterns across transplant centres. Retrospective data from the investigators' centre suggest DGF rates of approximately 30% with furosemide and 22% with mannitol, but these non-randomized data preclude definitive conclusions. The existing literature is limited by small sample sizes, retrospective designs, inconsistent dosing protocols, heterogeneous patient populations, and the absence of standardized outcome definitions. No adequately powered, prospective, randomized trial has compared furosemide head-to-head against mannitol. Multiple reviews have concluded that well designed prospective randomized data are needed. This pilot trial addresses that evidence gap by providing the first direct, randomized, blinded comparison of these two agents with standardized dosing and timing, generating feasibility data, effect-size estimates, and operational infrastructure to support a future definitive multicentre trial.
83 studies on the registry are indexed under Delayed Graft Function; 15 are open to participants now.
This study's planned enrollment of 160 is above the median of 90 across 62 interventional studies indexed under Delayed Graft Function.
Browse Delayed Graft Function studies →London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's is the lead sponsor of 331 studies on the registry; 137 are open to participants now.
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Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
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In the Furosemide arm, 80 mg IV will be administered at 10-15 minutes prior to reperfusion of the transplanted kidney.
Drug: Furosemide
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
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.
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.
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.
Time frame: From enrollment to the end of the study (1 year)
Consent Rate
Consent rate = number who consented ÷ number approached. Reported as a percentage.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: From the administration of study drug until the end of post-op day 7.
Early graft function
1\. To compare early graft function between groups, as measured by urine output in the first 24-72 hours, serum creatinine levels during postoperative days 1-7.
Time frame: From the time of enrollment up until post op day 7.
Postoperative dialysis requirement
2\. To compare postoperative dialysis requirements, including number and duration of dialysis sessions.
Time frame: Post-op day 0 until the end of enrollment (1 year)
Post-operative Outcomes
3\. To evaluate the incidence of perioperative complications, including electrolyte abnormalities, hypotension requiring vasopressor support, pulmonary edema, transfusion requirements, biopsy-proven rejection, and 30-day readmission
Time frame: Post-op day 0 until the end of post-op day 30
Survival
4\. To compare length of hospital stay and 1-year graft and patient survival between groups.
Time frame: Post-op day 0 up until post-op day 365 (1 year post enrollment)
Plan to share: No — Individual participant data are not currently planned to be shared with researchers outside the study team. Any future sharing of deidentified data would require approval from the research ethics board and all applicable institutional and privacy approvals.
Start is estimated for Sep 2026; primary completion for Aug 2028, 23 months later.
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Studies of the drugs tested here: Furosemide · Mannitol
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's →