Off-Clamp Versus On-Clamp Partial Nephrectomy: An Updated Systematic Review, Meta-Analysis and Meta-Regression

Objectives: The impact of renal ischemia during partial nephrectomy (PN) on postoperative renal function remains controversial. On-clamp PN provides improved surgical exposure and haemostasis but induces warm ischemia, which may impair renal function. Off-clamp PN avoids ischemia-related injury and may better preserve renal function, although concerns persist regarding blood loss and oncological safety. We systematically compared perioperative and functional outcomes, as well as surgical margin status between on-clamp and off-clamp PN. Methods: We performed a systematic search of PubMed, Embase, Cochrane, Web of Science, and Scopus to identify randomized controlled trials (RCTs) and observational studies comparing on-clamp versus off-clamp PN with no publication time limitations. Outcomes included estimated glomerular filtration rate (eGFR), percentage eGFR change, estimated blood loss (EBL), transfusion rates, positive surgical margins (PSMs), operative time, and complications. Results: Thirty-nine studies (four RCTs) including 10,154 patients were analysed. Off-clamp PN was associated with a smaller decline in eGFR (mean difference [MD] -4 mL/min/1.73 m², 95% CI -5.7 to -2.8) and lower percentage eGFR loss (MD -1.7%, 95% CI -2.8 to -0.7). On-clamp PN was associated with lower EBL (MD -48 mL, 95% CI -72 to -25). Transfusion rates favored on-clamp PN but were not statistically significant (OR 0.7, 95% CI 0.5-1.0). On-clamp PN was associated with a higher risk of PSM (OR 1.3, 95% CI 1.0-1.7) and postoperative complications (OR 1.3, 95% CI 1.1-1.6). Between-study heterogeneity and predominance of observational data were key limitations. Conclusions: Off-clamp PN provides superior renal functional preservation and lower risks of PSMs and complications, at the cost of increased blood loss. These findings support individualized surgical decision-making based on patient and tumor characteristics. What does the study add?: This study provides an extensive and detailed comparison of off-clamp versus on-clamp partial nephrectomy, encompassing more than 10,000 patients from 39 studies. By integrating the available evidence up to late 2024, it delivers comprehensive estimates of the renal functional benefits associated with ischemia-free surgery. Our findings delineate the trade-offs between renal preservation, blood loss, and surgical margin status, thereby informing individualised decision-making in nephron-sparing surgery and refining current understanding of when ischemia avoidance is most clinically advantageous. Patient summary: Our study suggests that performing partial nephrectomy without temporarily clamping the kidney blood vessels may better preserve kidney function and reduce cancer-related surgical risks, but can lead to increased blood loss during surgery. These findings indicate that the choice of surgical technique should be individualised, taking into account tumour features and patient-specific factors.