The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

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

OBJECTIVES: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). MATERIALS AND METHODS: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) 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. RESULTS: A 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. CONCLUSION: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.

Safety of on- vs off-clamp robotic partial nephrectomy: per-protocol analysis from the data of the CLOCK randomized trial.

PURPOSE: To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN). METHODS: 302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN (CLOCK trial-ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared. RESULTS: Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm, p < 0.001) and RENAL score (5 vs 6, p < 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml, p = 0.7), post-operative complications rate (19% vs 26%, p = 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%, p = 0.9; transfusion rate 3.4% vs 6.3%, p = 0.5; re-intervention due to bleeding 1.1% vs 4%, p = 0.4), acute kidney injury (4% vs 6%, p = 0.8), and positive surgical margins (3.5% vs 8.2%, p = 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09-0.52, p = 0.008). CONCLUSIONS: The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.

No ischemia technique, parenchymal preservation and age are the most important determinants of renal function after partial nephrectomy.

OBJECTIVE: The aim of the present study was to compare the outcomes of Off-Clamp to On -Clamp approach during robot-assisted partial nephrectomy (RAPN). MATERIEL AND METHODS: Retrospective study of 940 patients who underwent a RAPN between 2007 and 2015 for cT1a tumors using On-Clamp or Off-Clamp approaches. Patient with solitary kidney or multifocal were excluded. Overall, 103 patients underwent Off-Clamp approach and 37 patients On-Clamp approach. We matched the patients in terms of tumor size, Charlson comorbidity index and R.E.N.A.L. score. At all, 309 patients from the On-Clamp were matched to the Off-Clamp group. We compared the clinic-pathological characteristics, perioperative morbidity and late functional outcomes between the 2 propensity score matched groups. Limitation included retrospective analysis. RESULTS: After matching, there were no difference in clinic-pathological characteristics in terms of gender, age, race, body mass index, Charlson comorbidity index, American Society of Anesthesiologists score, baseline estimated glomerular filtration rate (e-GFR), tumor size, R.E.N.A.L. score complexity, hilar (H) location between the 2 groups. Regarding perioperative outcomes; while operative time (P=0,4), estimated blood loss (P=0,28), Clavien grade III-IV complications (P=0,8) surgical reoperation (P=1), 30-day readmission (P=1), positive surgical margin (5,5% vs. 5,8%, P=0,9) were comparable between the 2 groups, there were significant difference in excisional volume loss (median, 7,08 vs. 3,51cm3, P<0,01), e-GFR decline (median, -9,7 vs. -2,2ml/min/1,73 m2, P<0,01), percent of e-GFR preservation (median, 87% vs. 97%, P<0,01), and CKD upstaging (36,5% vs. 23,3%, P=0,01), Off-Clamp approach (P=0,01), and age (P=0,02) were predictors of renal function preservation, whereas excisional volume loss (OR=1,035, CI 95% (1,015-1,06), P<0,01) predicted upstaging. CONCLUSION: RAPN for selected renal mass using Off-Clamp approach offered renal functional advantage over On-Clamp, without adding morbidities. While no ischemia technique was associated with less excisional volume loss, Off-Clamp approach, and age were independent predictors of renal function preservation. Clinical significance of these findings in various clinical settings will require further investigation.

On-clamp versus off-clamp partial nephrectomy: Propensity score-matched comparison of long-term functional outcomes.

OBJECTIVES: To compare long-term functional outcomes of off-clamp or on-clamp partial nephrectomy patients of two high-volume centers with cT1-2/N0 M0 renal tumors and baseline estimated glomerular filtration rate >60 mL/min. METHODS: A 3:1 propensity score-matched analysis was used to select two homogeneous cohorts to compare off-clamp versus on-clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2-8-year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan-Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared. RESULTS: Overall, 1073 patients were included (588 on-clamp and 485 off-clamp). After applying the propensity score-matched analysis, the two cohorts of 157 on-clamp and 472 off-clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off-clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on-clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off-clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer-specific survival (P = 0.26) and overall survival (P = 0.18). CONCLUSIONS: Off-clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on-clamp partial nephrectomy presented a 7.3-fold increased risk of developing a severe chronic kidney disease during follow up.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

OBJECTIVES: To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. METHODS: A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. RESULTS: The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). CONCLUSION: We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered.

On-Clamp vs. Off-Clamp Robot-Assisted Partial Nephrectomy for cT2 Renal Tumors: Retrospective Propensity-Score-Matched Multicenter Outcome Analysis.

We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13−4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27−0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

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.

OBJECTIVES: We aimed to report the latest and largest pooled analysis and evidence update to compare the perioperative, renal functional, and oncological outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN) for renal tumors. PATIENTS AND METHODS: We performed a systematic literature search using PubMed, Embase, and Web of Science up to August 2021 for studies that compared the efficacy and/or safety between off-clamp and on-clamp RAPN for renal tumors. Outcomes measured were operating time, estimated blood loss (EBL), conversion rate, length of stay (LOS), complication rate, transfusion rate, long-term % decrease in estimated glomerular filtration rate (eGFR), positive surgical margin rate, and recurrence rate. RESULTS: A total of 21 eligible articles involving 4,493 patients (1,274 off-clamp versus 3,219 on-clamp) were included for the evidence synthesis. Baseline characteristics of the two groups were similar in all outcomes except that lower R.E.N.A.L. score and smaller tumor size were observed in the off-clamp group. Pooled analysis showed shorter operative time, higher EBL, and lower complication rate in the off-clamp group. No significant difference was observed in the conversion rate, LOS, and transfusion rate. The recurrence rates were similar in the two groups, while a lower positive surgical margin rate was observed in the off-clamp group. Finally, the off-clamp group had a superior postoperative renal functional outcome. CONCLUSIONS: Given the presence of heterogeneity and potential bias, urologists should select the clamp strategy based on their experience and patient-specific factors.

On-clamp versus off-clamp robotic partial nephrectomy: A systematic review and meta-analysis.

BACKGROUND: The debate on the pros and cons of robot-assisted partial nephrectomy performed with (on-clamp) or without (off-clamp) renal artery clamping is ongoing. The aim of this meta-analysis is to summarize the available evidence on the comparative studies assessing the outcomes of these two approaches. MATERIAL AND METHODS: A systematic review of the literature on PubMed, ScienceDirect®, and Embase® was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA). Only comparative and case-control studies were submitted to full-text assessment and meta-analysis. RevMan 5.3 software was used. RESULTS: From the initial retrieval of 1937 studies, 15 fulfilling inclusion criteria were selected and provided 2075 patients for analysis (702 off-clamp, 1373 on-clamp). Baseline tumor's features showed a significant difference in size (weighted mean difference: -0.58 cm; 95% confidence interval: [-1.06, -0.10]; p = 0.02) and R.E.N.A.L. score (weighted mean difference: -0.53; 95% confidence interval: [-0.81, -0.25]; p = 0.0002), but not in the exophytic property, the location, and the PADUA score. Pooled analysis revealed shorter operative time (p = 0.02) and higher estimated blood loss (p = 0.0002) for the off-clamp group. Overall complication and transfusion rates were similar, while higher major complication rate was observed in the on-clamp approach (5.6% vs 1.9%, p = 0.03). No differences in oncological outcomes were found. Finally, functional outcomes (assessed by estimated glomerular filtration rate at early postoperative, 3 month, 6 month, and last available follow-up) were not statistically different. CONCLUSION: This meta-analysis shows that off-clamp robot-assisted partial nephrectomy is reserved to smaller renal masses. Under such conditions, no differences with the on-clamp approach emerged.