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

Abstract

The benefit of intraoperative mannitol in patients undergoing nephron-sparing surgery (NSS) has been of recent clinical interest and investigation. Following a retrospective analysis at our center that showed no benefit of mannitol in renal function at 6 mo, we performed a prospective, randomized, placebo-controlled, double-blind, clinically integrated study to evaluate the role of mannitol at the time of NSS [1,2]. The trial design has been described

The use of mannitol in partial nephrectomy for renal function preservation: meta-analysis and systematic review of comparative studies

“…Recent studies have failed to demonstrate a benefit with the use of intravenous mannitol during PN. The results of this meta-analysis given the current available evidence suggest that there is no significant benefit in the preservation of renal function in patients undergoing PN at several time points, from 4–8 weeks to 6 months, to the longest recorded follow-ups in the trial conducted by Spaliviero et al 3 and reported by Wong et al 4…”

“…18 Recent studies have failed to demonstrate a benefit with the use of intravenous mannitol during PN. The results of this meta-analysis given the current available evidence suggest that there is no significant benefit in the preservation of renal function in patients undergoing PN at several time points, from 4-8 weeks to 6 months, to the longest recorded follow-ups in the trial conducted by Spaliviero et al 3 and reported by Wong et al 4 The limitations of this study include the small number of prospective randomised trials, despite the rigorous search and screening strategies employed. The quality of evidence was also noted to be poor, with the randomised studies having some concerns regarding the high risk of bias, and with the non-randomised studies noted to have a moderate to serious risk of bias.…”

“…The longest duration of follow-up among the studies included was 3 years, as reported by Wong and colleagues 4 in their post-hoc analysis of 3-year outcomes of the randomised trial reported by Spaliviero et al 3 The remaining studies assessed postoperative GFR at the longest follow-up ranging from 30 days to 6 months. Pooled estimates also showed no significant difference in percentage change from preoperative GFR (Figure 4).…”

“…Table 1 describes the titles, authors and study designs of the randomised and non-randomised studies. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] One randomised trial (EUCTR2012-003398-24-ES) is ongoing at the time of this paper. 5 The included, completed RCTs were assessed to have some concerns regarding a high risk of bias; while the non-RCTs were all retrospective studies with a moderate to serious concern for risk of bias.…”

Examining Mannitol Use in Kidney Cancer Surgery: A Cautionary Tale of Extrapolated Surgical Data

“…No difference in postsurgical eGFR was identified at 6 mo from baseline [38]. In a follow-up study of the phase 3 trial, longer-term outcomes were evaluated, including the impact in patients with CKD-again showing no impact of mannitol [39].…”