Intravenous Mannitol Versus Placebo During Partial Nephrectomy in Patients with Normal Kidney Function: A Double-blind, Clinically-integrated, Randomized Trial

Abstract

Background: Mannitol is currently used as a renal protective agent to mitigate the effects of renal ischemia during nephron-sparing surgery (NSS). This routine practice lacks rigorous methodological study.

Objective: To assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS.

Design, setting, participants: This prospective, randomized, placebo-controlled, double-blind trial included 199 patients with a preoperative estimated glomerular filtration rate (eGFR) >45ml/min/1.73m² scheduled for NSS; the trial was conducted between July 2012 and July 2015.

Intervention: Patients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping.

Outcome measurements and statistical analysis: The primary outcome was the difference in eGFR (renal function) between the two groups at 6 mo following surgery assessed with an analysis of covariance model using preoperative eGFR, treatment group, and surgical approach as covariates.

Results and limitations: At baseline, the median age of the patients was 58 yr, and the median eGFR was 88ml/min/1.73m². Comparing placebo with mannitol infusion, the adjusted difference of 0.2 eGFR units at 6 mo was not significant (p=0.9), with the upper bound of the 95% confidence interval (-3.1 to 3.5) excluding a clinically relevant effect of mannitol. Limitations include evaluation of a single mannitol dose and patients all had excellent preoperative renal function.

Conclusions: Intraoperative 12.5g mannitol infusion during NSS has no demonstrable clinical benefit when compared with standardized fluid hydration in patients with normal preoperative renal function, and its use in this setting is not warranted.

Patient summary: In this randomized trial, patients with normal kidney function who received mannitol during surgery to remove part of their kidney had no better kidney function 6 mo after surgery than those who did not receive mannitol. We conclude that this routine practice should be discontinued.

Trial registration: ClinicalTrials.gov NCT01606787.

Keywords: Mannitol; Nephron-sparing surgery; Partial nephrectomy; Renal function.

Fig. 1 –

Flow diagram for enrollment and randomization of trial. MD = medical doctor; preop = preoperative; RCC = renal cell carcinoma.

Fig. 2 –

Estimated glomerular filtration rate (eGFR) over the study period by treatment group. Small gold dots represent the observed eGFR in patients enrolled in the mannitol arm; small blue dots represent the observed eGFR in patients randomized to placebo. Large dots represent the treatment group means.