Presentation Authors: Nathan C. Wong*, Ricardo G. Alvim, Daniel D. Sjoberg, Roman Shingarev, New York, NY, Nicholas E. Power, London, Canada, Maximillian Spaliviero, Stony Brook, NY, Katie S. Murray, Columbia, MO, Nicole E. Benfante, A. Ari Hakimi, Paul Russo, Jonathan A. Coleman, New York, NY
Introduction: Our phase III trial demonstrated that patients who received mannitol during nephron sparing surgery (NSS) showed no better renal function at 6 months than those who received placebo. Despite these results, some have suggested that patients with comorbidities, including lower pre-operative estimated glomerular filtration rate (eGFR), may still derive some benefit. We sought to address this hypothesis by reanalyzing trial data and long-term renal function outcomes.
Methods: Between 2012-2015, 199 patients undergoing NSS with eGFR â‰¥45 mL/min/1.73 m2 were randomized 1:1 to receive mannitol or normal saline within 30 minutes of renal artery occlusion. The original endpoint was to assess differences in eGFR at 6 months. In this analysis, follow-up was extended to 3 years. Using ANCOVA, we assessed whether the effect of mannitol on post-operative eGFR was modified by pre-operative eGFR or other patient and surgical factors.
Results: 134 (67%) trial patients had eGFR available at 3 years. Patients missing from the follow-up analysis were not significantly different from the study population. Median pre-operative and 3-year post-operative eGFR in the mannitol arm were 86 and 77 mL/min/1.73m2 respectively vs. 89 and 79 ml/min/1.73m2. There was no significant difference between groups (mean GFR difference 1.4; 95% CI -2.6, 5.3; p=0.5). At both 6 months and 3 years, the effect of mannitol was not significantly modified by patient or surgical factors including pre-operative eGFR (p=0.3), coronary artery disease (0.15), diabetes (0.9), surgical approach (0.14), ischemia time (0.3), and tumor size (0.09). There was a small non-significant trend favoring mannitol in patients with higher pre-operative eGFR (Figure 1). There was also a non-significant trend favoring mannitol in larger tumors at 6 months; this relationship was reversed at 3 years (favored in smaller tumors), suggesting a random variation rather than a true effect.
Conclusions: Intra-operative use of mannitol does not improve either short- or long-term renal function in patients undergoing NSS. There is no evidence of effect modification by comorbidities, including lower pre-operative eGFR, supporting the validity of the original trial conclusions within the spectrum of diseases of this patient population.
Source of Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.