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Phase III Trial of Intravenous Mannitol Versus Placebo During Nephron-sparing Surgery: Post Hoc Analysis of 3-yr Outcomes.

ABSTRACT: Our recently reported phase III trial demonstrated that patients undergoing nephron-sparing surgery (NSS) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m² who received mannitol had no improvement in renal function at 6 mo compared with those who received placebo. Some authors have suggested that benefit is restricted to subgroups, such as those with comorbidities. We assessed whether preoperative eGFR, or other patient and surgical factors modified the effect of mannitol on postoperative outcomes at 6 mo and with extended follow-up. We also assessed whether mannitol was associated with differences in long-term GFR years after surgery. No significant difference between the mannitol or placebo groups (mean eGFR difference: 1.4; 95% confidence interval: -2.6, 5.3; p = 0.5) was found in the 134 patients with known eGFR at 3 yr after NSS. At both 6 mo and 3 yr, the effect of mannitol was not significantly modified by patient or surgical factors including preoperative eGFR. In summary, we validated our original trial conclusions by finding that intraoperative use of mannitol does not improve either short- or long-term renal function in patients undergoing NSS. Specifically, there is no evidence that comorbidities, including lower preoperative eGFR, modify the effect of mannitol. PATIENT SUMMARY: Use of mannitol at the time of partial nephrectomy does not improve either short- or long-term renal function even in patients with comorbidities, including lower preoperative renal function. The routine use of intraoperative mannitol should be discontinued.

SUBMITTER: Wong NC

PROVIDER: S-EPMC8560079 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMannitol 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.ObjectiveTo assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS.Design, setting, participantsThis 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.InterventionPatients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping.Outcome measurements and statistical analysisThe 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 limitationsAt 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.ConclusionsIntraoperative 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 summaryIn 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.

Project description:Background and Objectives: Published data from individual studies present conflicting evidence about the relationship between clinicopathological risk factors and oncological outcomes in renal cell cancer (RCC) following nephron-sparing surgery (NSS). This study was conducted to explore the potential risk factors for RCC progress after NSS. Methods: Studies published in PubMed, Web of Science, and EMBASE were systematically reviewed from inception to March 2019 to determine risk factors for RCC following NSS. The predictive ability of identified predictors was assessed by hazard ratios (HRs) with 95% confidence intervals (CIs). A fixed-effect or random-effect was used to pool the estimates. Subgroup analyses were performed to explore the source of heterogeneity. Results: Seventeen studies including 38,522 patients with RCC were analyzed. The meta-analysis indicated that positive surgical margin (pooled HR = 1.47; 95% CI:1.24-1.73; P < 0.001), higher Fuhrman grade (pooled HR = 1.58; 95% CI:1.10-2.28; P = 0.013), higher pathological stage (pooled HR = 1.72; 95% CI:1.40-2.12; P < 0.001) and large tumor size (pooled HR = 1.09; 95% CI:1.03-1.16; P = 0.003) were significantly associated with recurrence risk. However, age (pooled HR = 1.00; 95% CI: 1.00-1.01; P = 0.257), sex (male vs. female) (pooled HR = 1.04; 95% CI: 0.89-1.21; P = 0.605) and surgical approach (laparoscope vs. open) (pooled HR = 0.80; 95% CI: 0.59-1.07; P = 0.129) had no effect on recurrence after NSS. In addition, we found that positive surgical margin was significantly associated with recurrence-free survival (pooled HR = 1.87; 95% CI: 1.32-2.66; P < 0.001) and overall mortality (pooled HR = 1.15; 95% CI: 1.07-1.23; P < 0.001), as well as large tumor size for recurrence-free survival (pooled HR = 1.18; 95% CI: 1.06-1.30; P = 0.002)and overall mortality (pooled HR = 1.01; 95% CI: 1.00-1.02; P = 0.004). Conclusions: Unfavorable pathological characteristics were distinctly related to worse oncological outcomes in RCC patients following NSS. These results may contribute to proposed prediction models for RCC patients to aid in counseling and risk stratification.

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Phase III Trial of Intravenous Mannitol Versus Placebo During Nephron-sparing Surgery: Post Hoc Analysis of 3-yr Outcomes.

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