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

Condition(s) studied

Investigational drug(s) / intervention(s)

Furosemide: 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: 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.

Study 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.

Eligibility

Primary outcome measure(s)

• Recruitment rate — From enrollment to the end of the study (1 year)
  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 — From enrollment to the end of the study (1 year).
  Consent rate = number who consented ÷ number approached. Reported as a percentage.
• Protocol Adherence — From enrollment to end of study (1 year)
  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 — From enrollment to end of study (1 year)
  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.
• Delayed Graft Function (DGF) — From the administration of study drug until the end of post-op day 7.
  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).

Trial sites (2)

More London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's trials in Canada

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