AUA 2019: Phase III Trial of Intravenous Mannitol Versus Placebo During Nephron Sparing Surgery: 3-Year Outcomes

Chicago, IL ( Dr. Nathan C. Wong presented on the use of mannitol for nephron-sparing surgery. Dr. Wong began by referring to previous literature in which retrospective analysis showed no significant difference in eGFR between a patient who were given mannitol versus those who were not given mannitol. Additionally, he referred to his own previously published work which showed similar results in a prospective randomized control trial (results can be seen in the following image).  However, the author addressed the criticisms of his paper, in which some believed his work did not consider “at risk” patients such as those with pre-op CKD, larger and more complex tumors, prolonged clamp times, and other additional comorbidities. In the following study, Dr. Wong evaluates these shortcomings by including a thorough interaction analysis of the previous paper’s original data with a longer-term follow-up.

AUA 2019 randomized controlled trial level 1

This study included 199 patient who were randomized to either pre-clamp IV Mannitol or IV normal saline. The primary outcome variables evaluated were eGFR levels at 6 months and 3 years. Analysis of covariance (ANCOVA) was used to identify the interactions of certain “at risk” categorical (history of coronary artery disease, diabetes, and surgical approach (open vs MIS)) and continuous variables (clamp time, tumor size, and preoperative eGFR) on the use of mannitol for patients undergoing nephron-sparing surgery.
The results of data analysis are depicted in the following images. Upon initial analysis, patient characteristics for those who received IV mannitol and those who received IV normal saline were comparable in terms of age at surgery, history of diabetes, history of coronary artery disease, Pre-op eGFR, surgical approach, and tumor size. Using linear regression analysis, the use of mannitol was not a significant predictor of 6-month eGFR (β=-0.2;95%;CI=-3.5,3.1;p>0.9) or 3-year eGFR (β=1.4;95%CI=-2.6,5.3;p=0.5). On interaction analysis of categorical variables, there was no association of coronary artery disease, diabetes, or surgical technique on the effect of mannitol on post-operative eGFR at either 6 months or 3 years. Likewise, continuous variables such as clamp time (min), tumor size (cm) and Pre-op eGFR showed no interaction on the effect of mannitol on post-operative eGFR.

AUA 2019 mannitol vs placebo postop GFR

The author concluded by stating that mannitol showed no renal protection effect on eGFR at either 6 months or 3 years, nor did it prove more effective on higher risk patients. Overall, these results correlated with Dr. Wong’s previous study, and because of this, he stated mannitol use should be discontinued for a patient undergoing nephron-sparing surgery. He finished by thanking all the patients involved in the study as well as all other co-investigators. Dr. Wong was applauded on his work and upon questioning noted that Memorial Sloan Kettering Cancer Center no longer uses mannitol on any of their patients. Additionally, Dr. Wong was questioned on if these results applied to patients with higher grade CKD. In response, he declined this, but stated the data from the interaction of categorical variables with mannitol might suggest mannitol use is detrimental to patients with higher grade CKD if data is extrapolated; especially given that the use of mannitol can potentially increase the metabolic demand of the renal system.

Presented by: Nathan C. Wong MD, Urologic Oncology Fellow, Memorial Sloan Kettering Cancer Center, New York, New York 

Written by: Luke Limfueco, Department of Urology, University of California-Irvine, at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois