Is off‐clamp robot‐assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial

Abstract

To compare the functional outcomes of on-vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). Materials and MethodsThe CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT 02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre-and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed. ResultsA total of 160 and 164 patients were randomly assigned to on-and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on-and off-clamp arms, respectively. We were unable to find any statistically significant difference between on-vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR −6.2 vs −5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] −3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR −6.8 vs −4.2 mL/min, mean difference 1.6 mL/min, 95% CI −2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis. ConclusionIn patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on-vs off-clamp RAPN.

Comparison of Perioperative, Renal Functional, and Oncological Outcomes Between Off-Clamp and On-Clamp Robot-Assisted Partial Nephrectomy for Renal Tumors: An Updated Evidence-Based Analysis

“…Although there was significant heterogeneity in the long-term % decrease in eGFR, the difference remained significant when we excluded the main sources of heterogeneity (WMD: -4.48; 95% CI: -6.14, -2.82; p < 0.00001). However, it is worth noting that superior functional outcomes of the off-clamp group which are reported by previous observational studies (11,13,24) have not been confirmed in any RCTs (22,28), indicating potential selection bias in our meta-analysis. Moreover, short-term renal functional outcomes after RAPN are still controversial (12,15).…”

“…Notwithstanding several limitations of our study, we reported the latest and largest meta-analysis that added six novel articles (four cohort studies (24,25,27,29) and two prospective randomized studies (26,28) published during 2019-2021 on the bases of previous studies, which makes our evidence more credible. Our evidence-based analysis validated previous studies reporting the superiority of the off-clamp technique in RAPN (9,10,12,20), especially in patients who require preservation of renal function (e.g., solitary kidney or chronic kidney disease) (23).…”

“…Finally, 21 full-text articles involving 4,493 patients (1,274 off-clamp versus 3,219 on-clamp) were included for the pooled analysis . Of these articles, 7 were prospective cohort studies (9,10,12,13,16,18,25,27), 10 were retrospective cohort studies (11, 14, 15, 17, 19-21, 23, 24, 29), and 3 were prospective randomized studies (22,26,28). Table 1 shows the characteristics, level of evidence, and quality score of each included study.…”

“…There were two published meta-analyses that compared the efficacy and safety of on-clamp and off-clamp RAPN, which both did not assert that the off-clamp approach is the optimal clamping technique in RAPN (30,31). Whereafter, six novel original studies of the same topic have been published during 2019-2020 (24)(25)(26)(27)(28)(29). Thus, we reported a pooled analysis and evidence update to compare the perioperative, renal functional, and oncological outcomes between off-clamp and on-clamp RAPN for renal tumors.…”

Retroperitoneal Robot-assisted Partial Nephrectomy: A Systematic Review and Pooled Analysis of Comparative Outcomes

“…In our analysis, no differences were observed regarding WIT in both approaches. In a recent randomized clinical trial, Antonelli et al [37] compared the functional outcomes of on- versus off-clamp RAPN performed with the retroperitoneal and transperitoneal approaches. The authors found no differences between clamp techniques in terms of absolute variation of GFR at 6, 12, 18, and 24 mo.…”