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.
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
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)
Parallel
Furosemide
DrugFurosemide 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
DrugMannitol 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.
Consent Rate
Consent rate = number who consented ÷ number approached. Reported as a percentage.
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.
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.
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.
Postoperative dialysis requirement
2\. To compare postoperative dialysis requirements, including number and duration of dialysis sessions.
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
Survival
4\. To compare length of hospital stay and 1-year graft and patient survival between groups.
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