Effect of multiple renal artery clamping on postoperative renal function in robot-assisted partial nephrectomy: A propensity-matched study

Effect of multiple renal artery clamping on postoperative renal function in robot-assisted partial nephrectomy: A propensity-matched study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of multiple renal artery clamping on postoperative renal function in robot-assisted partial nephrectomy: A propensity-matched study Tomoyuki Tatenuma, Kota Kobayashi, Ryosuke Jikuya, Go Noguchi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8153981/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Journal of Robotic Surgery → Version 1 posted 11 You are reading this latest preprint version Abstract Objective To evaluate the effect of clamping multiple renal arteries on postoperative renal function in patients undergoing robot-assisted partial nephrectomy (RAPN). Methods A retrospective review of 694 patients who underwent RAPN for renal tumors between March 2016 and June 2023 was conducted. The patients were categorized into single and multiple clamp cohorts. Baseline differences were minimized using 1:1 propensity score matching. Renal function was evaluated using estimated glomerular filtration rate (eGFR) at 7 days and 1, 3, and 12 months postoperatively. Additionally, acute kidney injury (AKI), chronic kidney disease (CKD) progression, and dialysis requirements were evaluated. Statistical significance was defined as p < 0.05. Results After matching, 26 patients were included in each group. There were no significant differences in perioperative outcomes, including warm ischemia time, trifecta achievement, and surgical margin status. Despite a longer operative time in the multiple clamp group, no adverse effects on renal function were observed. There were no significant group differences in the eGFR at any time point or in the rates of AKI, CKD progression, or dialysis requirement. Conclusion Clamping of multiple renal arteries during RAPN did not appear to negatively affect short- or long-term postoperative renal function. Multiple clamping may be an acceptable technique for achieving a bloodless surgical field when necessary. Multiple clamping robot-assisted partial nephrectomy renal function propensity score matching Figures Figure 1 Introduction In patients diagnosed with localized renal cell carcinoma (RCC), partial or radical nephrectomy remains the primary therapeutic approach. Evidence from systematic reviews indicates that both procedures offer comparable cancer-specific survival rates in patients with T1a RCC, 1 although partial nephrectomy (PN) is associated with reduced overall and non-cancer-related mortalities compared with radical nephrectomy. 2 Since the initial report on laparoscopic PN by Winfield et al. in 1993, 3 open surgical techniques have gradually been replaced by minimally invasive approaches. This evolution continued with the introduction of robot-assisted PN (RAPN) by Gettman et al. in 2004, 4 which significantly improved surgical precision and minimized invasiveness. Renal artery clamping, commonly performed to achieve a bloodless surgical field during PN, makes the kidney susceptible to ischemic injury. 5 Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) in PN. 6 In particular, multiple artery clamping can lead to IRI, triggering a cascade of tissue injury events. Therefore, it is generally considered that renal artery clamping should be performed only once. However, few studies have examined the relationship between multiple renal artery clamping and renal function. This study aimed to clarify whether multiple-artery clamping affects renal outcomes in patients undergoing RAPN. Materials and Methods Study design and population We retrospectively analyzed 694 patients who underwent RAPN at the Yokohama City University Hospital between March 2016 and June 2023. During the surgery, primary renal arteries were clamped using bulldog clamps. If Doppler ultrasound indicated continued perfusion, the clamps were temporarily removed to identify and secure additional arteries. Multiple clamping procedures were performed in these patients. This brief clamping time was not included in the calculation of warm ischemia time (WIT) in a multiple clamp group. Ten operators performed RAPN using this clamping approach. To reduce the risk of carbon dioxide embolism and ensure a clear surgical field despite intraoperative bleeding, both the renal artery and vein were clamped as needed. 7 The renal cortex was incised using a cold-cut method, and the medulla was bluntly separated. Arterial branches were coagulated using a sealing device whenever possible. No tumor enucleation was performed. Instead, the excision line was selected close to the enucleation site, particularly when the tumor was adjacent to the renal sinus. When large vessels or collecting systems were encountered, continuous suturing with 3 − 0 barbed sutures was applied. Renorrhaphy was performed in all the patients using continuous suturing using 1 − 0 barbed sutures. Early unclamping technique was performed in March, 2021. Data collection Renal function was assessed using estimated glomerular filtration rate (eGFR), which was calculated using the Japanese modified MDRD equation. eGFR = 194 × serum creatinine⁻¹·⁰⁹⁴ × age⁻⁰·²⁸⁷ × 0.739 (if female). 8 AKI was defined as a > 25% reduction in eGFR from baseline or a > 1.5-fold increase in serum creatinine during postoperative hospital stay, based on the risk, injury, failure, loss, and end-stage (RIFLE) criteria. 9 Renal function was monitored by evaluating the percentage change in eGFR at 7 days and 1, 3, and 12 months postoperatively. Outcome definitions Trifecta was defined as achieving all of the following: Negative surgical margins on pathology, WIT ≤ 25 min, and no perioperative Clavien–Dindo grade ≥ 3 complications. Chronic kidney disease (CKD) progression was defined as an increase from baseline CKD stage 1 or 2 to stage ≥ 3, stage 3 to ≥ 4, and stages 4 to 5. Pentafecta included the Trifecta criteria plus no progression in CKD stage and < 10% reduction in predicted postoperative eGFR. Patient characteristics, such as age, sex, body mass index (BMI), preoperative eGFR, American Society of Anesthesiologists (ASA) score, presence of diabetes mellitus and hypertension, and RENAL nephrometry score 10 were adjusted between groups using 1:1 propensity score matching. Statistical analysis Continuous variables with a normal distribution were analyzed using the Student’s t-test and presented as means with standard deviations. Non-normally distributed variables were assessed using the Mann–Whitney U test and reported as medians with interquartile ranges. Group comparisons were performed using the Mann–Whitney U test and Pearson’s chi-square test. Propensity scores were calculated using a multivariate logistic regression. All the analyses were conducted using EZR in the R software (version 1.55, Saitama Medical Center, Jichi Medical University). Statistical significance was set at p < 0.05. Results A total of 694 patients were included in this analysis. Of these, 667 were assigned to a single clamp group and 27 to a multiple clamp group. In the multiple clamp group, 24 patients were clamped twice, two were clamped three times, and one was clamped five times. Median duration of individual brief clamping in the multiple clamp group was 2 min (range, 1–10 min). Baseline characteristics of the two groups are summarized in Table 1. There were no significant differences between the groups in terms of age, sex, BMI, ASA classification, presence of hypertension or diabetes, tumor laterality, tumor size, clinical T stage, preoperative eGFR, or CKD stage. In a propensity score-matched cohort, which included 26 patients from each group, demographic and tumor-related characteristics remained comparable between the two groups. Perioperative data are summarized in Table 2. The multiple clamp had a longer operation time than the single clamp group (p = 0.065). However, no significant differences were observed in the surgical approach, WIT, proportion achieving WIT < 25 min, estimated blood loss, trifecta outcomes, and incidence of positive surgical margins. A propensity score-matched cohort showed no significant differences in perioperative outcomes, including operative time. Postoperative outcomes, including renal function, incidence of AKI, CKD stage progression, and introduction of dialysis, are presented in Table 3. No significant differences were found between the groups, either before or after matching, in terms of AKI rates, eGFR at 7 days and 1 year postoperatively, renal function preservation at 1 year, CKD progression, or dialysis introduction. Figure 1 shows changes in eGFR over time for both the entire and matched groups, with no significant differences observed at any time point. Discussion IRI is a major cause of AKI, particularly in patients with renal transplantation, PN, and cardiovascular surgery. 6 The pathogenesis of IRI is complex and involves a biphasic mechanism. Initially, ischemia leads to cellular depletion of adenosine triphosphate, loss of ion homeostasis, and accumulation of metabolic waste products. Paradoxically, the restoration of blood flow during reperfusion exacerbates renal damage through the generation of reactive oxygen species, activation of pro-inflammatory cytokines, and infiltration of immune cells. 11 , 12 Experimental studies have demonstrated that oxidative stress, endothelial dysfunction, and immune-mediated injury are key contributors to renal IRI progression. 13 In particular, innate and adaptive immune responses play critical roles in amplifying renal tissue injury during reperfusion. 14 Clinical evidence indicates that renal tissue can safely endure warm ischemia for up to 25 min, and cold ischemia—achieved by placing the kidney in ice slush—for approximately 35 min, with some tolerance extending to 2 h. 15 Prolonged ischemia beyond these thresholds may lead to irreversible cellular damage, contributing to nephron loss and CKD development in approximately 5–17% of cases. 15 Despite extensive studies on pharmacological interventions, such as calcium channel blockers, mannitol, acadesine, adenosine, sodium/hydrogen exchange inhibitors, and the antioxidant N-acetylcysteine, none have demonstrated consistent efficacy in preventing IRI in large animal models or human clinical trials, although promising results have been observed in rodent studies. 16 – 19 Ischemic preconditioning (IPC) is a protective physiological mechanism whereby brief, non-lethal episodes of ischemia render tissues more resistant to subsequent prolonged ischemic insults. This adaptive response was first described in the heart by Murry et al. in 1986, 20 and has since been demonstrated in various organs, including the kidneys. 21 IPC can be categorized as local, applied directly to the target organ, or remote, induced in a distant organ to provide systemic protection. 22 Remote IPC (RIPC) is a technique involving brief, controlled episodes of ischemia and reperfusion applied to a distant organ or tissue with the aim of inducing systemic protective effects against acute ischemic injury in vital organs. Despite its theoretical benefits, clinical evidence remains inconclusive. For example, Chung et al. conducted a randomized controlled trial and found no statistically significant differences in serum creatinine levels between patients who underwent RIPC and those in a control group on postoperative day 1 or at any subsequent time point following PN. 23 In contrast, Zager et al. reported how prior exposure to kidney ischemia in rats by intermittent clamping (IC) of bilateral renal arteries protected against subsequent ischemic injury in 1984. 24 However, IC does not confer resistance to warm ischemia in a solitary porcine kidney model. 25 This study involves a type of IC and suggests that it may not have a significant negative effect on renal function. Nevertheless, this study has several limitations. First, it was a retrospective analysis conducted at a single institution, and the sample size was relatively small. Propensity score matching was used to reduce potential biases. Second, renal function was evaluated using eGFR rather than renal scintigraphy of the affected kidney. Although eGFR may be less accurate, it remains a commonly used metric in clinical settings for assessing renal function after PN. Third, most patients in this cohort had preserved renal function, with eGFR values > 60 mL/min/1.73 m². Therefore, the effect of multiple clamps on individuals with preexisting renal dysfunction could not be determined. Finally, in cases where residual blood flow was observed after clamping, the artery was released, leading to a relatively short initial ischemic period. Therefore, the effects of prolonged clamping or repeated clamping on renal function remain unclear. Conclusion Multiple renal artery clamping did not adversely affect the postoperative renal function following RAPN, either in the short or long term. This technique may achieve a bloodless surgical field during PN. Declarations Funding: No funding was received for this study Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions: Tomoyuki Tatenuma: Conceptualization, writing the original draft, writing the review and editing, investigation, formal analysis, and data curation. Kota Kobayashi: Data curation. Ryosuke Jikuya Data curation. Go Noguchi Data Curation. Hiroki Ito: Data curation. Komeya Mitsuru Data Curation. Yusuke Ito: Data curation. Kentaro Muraoka Data curation. Hisashi Hasumi Data curation. Kazuhide Makiyama : Project administration. Ethics approval: The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Institutional Review Board of Yokohama City University, Approval No. F231000006. Informed consent; This study was retrospective study; we applied Opt-out method to obtain consent on this study. References MacLennan S, Imamura M, Lapitan MC, et al (2012) Systematic review of oncological outcomes following surgical management of localised renal cancer. Eur Urol 61:972–993. https://doi.org/10.1016/j.eururo.2012.02.039 Zini L, Perrotte P, Capitanio U, et al (2009) Radical versus partial nephrectomy: effect on overall and non-cancer mortality. Cancer 115:1465–1471. https://doi.org/10.1002/cncr.24035 Winfield HN, Donovan JF, Godet AS, Clayman RV (1993) Laparoscopic partial nephrectomy: initial case report for benign disease. J Endourol 7:521–526. https://doi.org/10.1089/end.1993.7.521 Gettman MT, Blute ML, Chow GK, et al (2004) Robotic-assisted laparoscopic partial nephrectomy: technique and initial clinical experience with DaVinci robotic system. 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Circulation 106:2881–2883. https://doi.org/10.1161/01.cir.0000043806.51912.9b Chung J, et al (2021) The effect of remote ischemic preconditioning on serum creatinine in patients undergoing partial nephrectomy: a randomized controlled trial. J Clin Med 10:1636. https://doi.org/10.3390/jcm10081636 Zager RA, Johnson AC, et al (1984) Responses of the ischemic acute renal failure kidney to additional ischemic events. Kidney Int 26:689–700. https://doi.org/10.1038/ki.1984.204 Orvieto MA, et al (2007) Ischemia preconditioning does not confer resilience to warm ischemia in a solitary porcine kidney model. Urology 69:984–987. https://doi.org/10.1016/j.urology.2007.01.100 Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.xlsx Table 1. Clinical and demographic characteristics between single and multiple clamp groups Table 2. Perioperative, oncologic, and trifecta achievement outcomes in single and multiple clamp groups Table 3. Postoperative renal function and achievement outcomes in single and multiple clamp groups Cite Share Download PDF Status: Published Journal Publication published 05 Jan, 2026 Read the published version in Journal of Robotic Surgery → Version 1 posted Editorial decision: Revision requested 02 Dec, 2025 Reviews received at journal 02 Dec, 2025 Reviewers agreed at journal 29 Nov, 2025 Reviews received at journal 28 Nov, 2025 Reviewers agreed at journal 28 Nov, 2025 Reviewers agreed at journal 28 Nov, 2025 Reviewers agreed at journal 28 Nov, 2025 Reviewers invited by journal 28 Nov, 2025 Editor assigned by journal 22 Nov, 2025 Submission checks completed at journal 21 Nov, 2025 First submitted to journal 19 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8153981","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":552902756,"identity":"305db1d1-4c1d-40b9-b2a9-f53388db5a13","order_by":0,"name":"Tomoyuki 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1","display":"","copyAsset":false,"role":"figure","size":76286,"visible":true,"origin":"","legend":"\u003cp\u003eChange in eGFR among total and propensity score matched cohorts of RAPN with single and multiple clamps.\u003c/p\u003e\n\u003cp\u003eeGFR, estimated glomerular filtration rate; RAPN, robot-assisted partial nephrectomy\u003c/p\u003e","description":"","filename":"Figure.png","url":"https://assets-eu.researchsquare.com/files/rs-8153981/v1/8558fc5a67c70c79d511ac11.png"},{"id":100070121,"identity":"2640fe34-adb9-40f4-b7b9-4d643f87fcba","added_by":"auto","created_at":"2026-01-12 16:16:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":475747,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8153981/v1/901afade-0bc4-4056-a0f5-274a82336b3a.pdf"},{"id":97266625,"identity":"4a8cb65c-f064-4b35-a121-e6c42889400d","added_by":"auto","created_at":"2025-12-02 14:35:01","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15516,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1\u003cstrong\u003e.\u003c/strong\u003e Clinical and demographic characteristics between single and multiple clamp groups\u003c/p\u003e\n\u003cp\u003eTable 2\u003cstrong\u003e.\u003c/strong\u003e Perioperative, oncologic, and trifecta achievement outcomes in single and multiple clamp groups\u003c/p\u003e\n\u003cp\u003eTable 3. Postoperative renal function and achievement outcomes in single and multiple clamp groups\u003c/p\u003e","description":"","filename":"Table.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8153981/v1/9f7813c43d4dfe2d8c3956d2.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of multiple renal artery clamping on postoperative renal function in robot-assisted partial nephrectomy: A propensity-matched study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn patients diagnosed with localized renal cell carcinoma (RCC), partial or radical nephrectomy remains the primary therapeutic approach. Evidence from systematic reviews indicates that both procedures offer comparable cancer-specific survival rates in patients with T1a RCC,\u003csup\u003e1\u003c/sup\u003e although partial nephrectomy (PN) is associated with reduced overall and non-cancer-related mortalities compared with radical nephrectomy.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSince the initial report on laparoscopic PN by Winfield et al. in 1993,\u003csup\u003e3\u003c/sup\u003e open surgical techniques have gradually been replaced by minimally invasive approaches. This evolution continued with the introduction of robot-assisted PN (RAPN) by Gettman et al. in 2004,\u003csup\u003e4\u003c/sup\u003e which significantly improved surgical precision and minimized invasiveness.\u003c/p\u003e\u003cp\u003eRenal artery clamping, commonly performed to achieve a bloodless surgical field during PN, makes the kidney susceptible to ischemic injury.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) in PN.\u003csup\u003e6\u003c/sup\u003e In particular, multiple artery clamping can lead to IRI, triggering a cascade of tissue injury events. Therefore, it is generally considered that renal artery clamping should be performed only once. However, few studies have examined the relationship between multiple renal artery clamping and renal function. This study aimed to clarify whether multiple-artery clamping affects renal outcomes in patients undergoing RAPN.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eStudy design and population\u003c/p\u003e\u003cp\u003eWe retrospectively analyzed 694 patients who underwent RAPN at the Yokohama City University Hospital between March 2016 and June 2023.\u003c/p\u003e\u003cp\u003eDuring the surgery, primary renal arteries were clamped using bulldog clamps. If Doppler ultrasound indicated continued perfusion, the clamps were temporarily removed to identify and secure additional arteries. Multiple clamping procedures were performed in these patients. This brief clamping time was not included in the calculation of warm ischemia time (WIT) in a multiple clamp group. Ten operators performed RAPN using this clamping approach.\u003c/p\u003e\u003cp\u003eTo reduce the risk of carbon dioxide embolism and ensure a clear surgical field despite intraoperative bleeding, both the renal artery and vein were clamped as needed.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The renal cortex was incised using a cold-cut method, and the medulla was bluntly separated. Arterial branches were coagulated using a sealing device whenever possible. No tumor enucleation was performed. Instead, the excision line was selected close to the enucleation site, particularly when the tumor was adjacent to the renal sinus. When large vessels or collecting systems were encountered, continuous suturing with 3\u0026thinsp;\u0026minus;\u0026thinsp;0 barbed sutures was applied. Renorrhaphy was performed in all the patients using continuous suturing using 1\u0026thinsp;\u0026minus;\u0026thinsp;0 barbed sutures. Early unclamping technique was performed in March, 2021.\u003c/p\u003e\u003cp\u003eData collection\u003c/p\u003e\u003cp\u003eRenal function was assessed using estimated glomerular filtration rate (eGFR), which was calculated using the Japanese modified MDRD equation.\u003c/p\u003e\u003cp\u003eeGFR\u0026thinsp;=\u0026thinsp;194 \u0026times; serum creatinine⁻\u0026sup1;\u0026middot;⁰⁹⁴ \u0026times; age⁻⁰\u0026middot;\u0026sup2;⁸⁷ \u0026times; 0.739 (if female).\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAKI was defined as a\u0026thinsp;\u0026gt;\u0026thinsp;25% reduction in eGFR from baseline or a\u0026thinsp;\u0026gt;\u0026thinsp;1.5-fold increase in serum creatinine during postoperative hospital stay, based on the risk, injury, failure, loss, and end-stage (RIFLE) criteria.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Renal function was monitored by evaluating the percentage change in eGFR at 7 days and 1, 3, and 12 months postoperatively.\u003c/p\u003e\u003cp\u003eOutcome definitions\u003c/p\u003e\u003cp\u003eTrifecta was defined as achieving all of the following: Negative surgical margins on pathology, WIT\u0026thinsp;\u0026le;\u0026thinsp;25 min, and no perioperative Clavien\u0026ndash;Dindo grade\u0026thinsp;\u0026ge;\u0026thinsp;3 complications. Chronic kidney disease (CKD) progression was defined as an increase from baseline CKD stage 1 or 2 to stage\u0026thinsp;\u0026ge;\u0026thinsp;3, stage 3 to \u0026ge;\u0026thinsp;4, and stages 4 to 5. Pentafecta included the Trifecta criteria plus no progression in CKD stage and \u0026lt;\u0026thinsp;10% reduction in predicted postoperative eGFR. Patient characteristics, such as age, sex, body mass index (BMI), preoperative eGFR, American Society of Anesthesiologists (ASA) score, presence of diabetes mellitus and hypertension, and RENAL nephrometry score\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e were adjusted between groups using 1:1 propensity score matching.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables with a normal distribution were analyzed using the Student\u0026rsquo;s t-test and presented as means with standard deviations. Non-normally distributed variables were assessed using the Mann\u0026ndash;Whitney U test and reported as medians with interquartile ranges. Group comparisons were performed using the Mann\u0026ndash;Whitney U test and Pearson\u0026rsquo;s chi-square test. Propensity scores were calculated using a multivariate logistic regression. All the analyses were conducted using EZR in the R software (version 1.55, Saitama Medical Center, Jichi Medical University). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 694 patients were included in this analysis. Of these, 667 were assigned to a single clamp group and 27 to a multiple clamp group. In the multiple clamp group, 24 patients were clamped twice, two were clamped three times, and one was clamped five times. Median duration of individual brief clamping in the multiple clamp group was 2 min (range, 1\u0026ndash;10 min). Baseline characteristics of the two groups are summarized in Table\u0026nbsp;1. There were no significant differences between the groups in terms of age, sex, BMI, ASA classification, presence of hypertension or diabetes, tumor laterality, tumor size, clinical T stage, preoperative eGFR, or CKD stage.\u003c/p\u003e\u003cp\u003eIn a propensity score-matched cohort, which included 26 patients from each group, demographic and tumor-related characteristics remained comparable between the two groups.\u003c/p\u003e\u003cp\u003ePerioperative data are summarized in Table\u0026nbsp;2. The multiple clamp had a longer operation time than the single clamp group (p\u0026thinsp;=\u0026thinsp;0.065). However, no significant differences were observed in the surgical approach, WIT, proportion achieving WIT\u0026thinsp;\u0026lt;\u0026thinsp;25 min, estimated blood loss, trifecta outcomes, and incidence of positive surgical margins. A propensity score-matched cohort showed no significant differences in perioperative outcomes, including operative time.\u003c/p\u003e\u003cp\u003ePostoperative outcomes, including renal function, incidence of AKI, CKD stage progression, and introduction of dialysis, are presented in Table\u0026nbsp;3. No significant differences were found between the groups, either before or after matching, in terms of AKI rates, eGFR at 7 days and 1 year postoperatively, renal function preservation at 1 year, CKD progression, or dialysis introduction. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows changes in eGFR over time for both the entire and matched groups, with no significant differences observed at any time point.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIRI is a major cause of AKI, particularly in patients with renal transplantation, PN, and cardiovascular surgery.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The pathogenesis of IRI is complex and involves a biphasic mechanism. Initially, ischemia leads to cellular depletion of adenosine triphosphate, loss of ion homeostasis, and accumulation of metabolic waste products. Paradoxically, the restoration of blood flow during reperfusion exacerbates renal damage through the generation of reactive oxygen species, activation of pro-inflammatory cytokines, and infiltration of immune cells.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Experimental studies have demonstrated that oxidative stress, endothelial dysfunction, and immune-mediated injury are key contributors to renal IRI progression.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e In particular, innate and adaptive immune responses play critical roles in amplifying renal tissue injury during reperfusion.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eClinical evidence indicates that renal tissue can safely endure warm ischemia for up to 25 min, and cold ischemia\u0026mdash;achieved by placing the kidney in ice slush\u0026mdash;for approximately 35 min, with some tolerance extending to 2 h.\u003csup\u003e15\u003c/sup\u003e Prolonged ischemia beyond these thresholds may lead to irreversible cellular damage, contributing to nephron loss and CKD development in approximately 5\u0026ndash;17% of cases.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Despite extensive studies on pharmacological interventions, such as calcium channel blockers, mannitol, acadesine, adenosine, sodium/hydrogen exchange inhibitors, and the antioxidant N-acetylcysteine, none have demonstrated consistent efficacy in preventing IRI in large animal models or human clinical trials, although promising results have been observed in rodent studies.\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIschemic preconditioning (IPC) is a protective physiological mechanism whereby brief, non-lethal episodes of ischemia render tissues more resistant to subsequent prolonged ischemic insults. This adaptive response was first described in the heart by Murry et al. in 1986,\u003csup\u003e20\u003c/sup\u003e and has since been demonstrated in various organs, including the kidneys.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e IPC can be categorized as local, applied directly to the target organ, or remote, induced in a distant organ to provide systemic protection.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Remote IPC (RIPC) is a technique involving brief, controlled episodes of ischemia and reperfusion applied to a distant organ or tissue with the aim of inducing systemic protective effects against acute ischemic injury in vital organs. Despite its theoretical benefits, clinical evidence remains inconclusive. For example, Chung et al. conducted a randomized controlled trial and found no statistically significant differences in serum creatinine levels between patients who underwent RIPC and those in a control group on postoperative day 1 or at any subsequent time point following PN.\u003csup\u003e23\u003c/sup\u003e In contrast, Zager et al. reported how prior exposure to kidney ischemia in rats by intermittent clamping (IC) of bilateral renal arteries protected against subsequent ischemic injury in 1984.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e However, IC does not confer resistance to warm ischemia in a solitary porcine kidney model.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e This study involves a type of IC and suggests that it may not have a significant negative effect on renal function.\u003c/p\u003e\u003cp\u003eNevertheless, this study has several limitations. First, it was a retrospective analysis conducted at a single institution, and the sample size was relatively small. Propensity score matching was used to reduce potential biases. Second, renal function was evaluated using eGFR rather than renal scintigraphy of the affected kidney. Although eGFR may be less accurate, it remains a commonly used metric in clinical settings for assessing renal function after PN. Third, most patients in this cohort had preserved renal function, with eGFR values\u0026thinsp;\u0026gt;\u0026thinsp;60 mL/min/1.73 m\u0026sup2;. Therefore, the effect of multiple clamps on individuals with preexisting renal dysfunction could not be determined. Finally, in cases where residual blood flow was observed after clamping, the artery was released, leading to a relatively short initial ischemic period. Therefore, the effects of prolonged clamping or repeated clamping on renal function remain unclear.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMultiple renal artery clamping did not adversely affect the postoperative renal function following RAPN, either in the short or long term. This technique may achieve a bloodless surgical field during PN.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study\u003c/p\u003e\n\u003cp\u003eCompeting Interests:\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions:\u003c/p\u003e\n\u003cp\u003eTomoyuki Tatenuma: Conceptualization, writing the original draft, writing the review and editing, investigation, formal analysis, and data curation. Kota Kobayashi: Data curation. Ryosuke Jikuya Data curation. Go Noguchi Data Curation. Hiroki Ito: Data curation. Komeya Mitsuru Data Curation. Yusuke Ito: Data curation. Kentaro Muraoka Data curation. Hisashi Hasumi Data curation. Kazuhide Makiyama\u003cstrong\u003e:\u003c/strong\u003e Project administration.\u003c/p\u003e\n\u003cp\u003eEthics approval:\u003c/p\u003e\n\u003cp\u003eThe protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Institutional Review Board of Yokohama City University, Approval No. F231000006.\u003c/p\u003e\n\u003cp\u003eInformed consent;\u003c/p\u003e\n\u003cp\u003eThis study was retrospective study; we applied Opt-out method to obtain consent on this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMacLennan S, Imamura M, Lapitan MC, et al (2012) Systematic review of oncological outcomes following surgical management of localised renal cancer. Eur Urol 61:972\u0026ndash;993. https://doi.org/10.1016/j.eururo.2012.02.039 \u003c/li\u003e\n\u003cli\u003eZini L, Perrotte P, Capitanio U, et al (2009) Radical versus partial nephrectomy: effect on overall and non-cancer mortality. Cancer 115:1465\u0026ndash;1471. https://doi.org/10.1002/cncr.24035 \u003c/li\u003e\n\u003cli\u003eWinfield HN, Donovan JF, Godet AS, Clayman RV (1993) Laparoscopic partial nephrectomy: initial case report for benign disease. J Endourol 7:521\u0026ndash;526. https://doi.org/10.1089/end.1993.7.521 \u003c/li\u003e\n\u003cli\u003eGettman MT, Blute ML, Chow GK, et al (2004) Robotic-assisted laparoscopic partial nephrectomy: technique and initial clinical experience with DaVinci robotic system. Urology 64:914\u0026ndash;918. https://doi.org/10.1016/j.urology.2004.06.049 \u003c/li\u003e\n\u003cli\u003eLane BR, Babineau DC, Poggio ED, Weight CJ, Larson BT, Gill IS, Novick AC (2008) Factors predicting renal functional outcome after partial nephrectomy. J Urol 180:2363\u0026ndash;2369. https://doi.org/10.1016/j.juro.2008.08.036 \u003c/li\u003e\n\u003cli\u003eZuk A, Bonventre JV (2016) Acute kidney injury. Annu Rev Med 67:293\u0026ndash;307. https://doi.org/10.1146/annurev-med-050214-013407 \u003c/li\u003e\n\u003cli\u003eMuraoka K, Jikuya R, Uemura K, et al (2024) Comparison of renal function between the artery and vein clamp and artery-only clamp in robot-assisted partial nephrectomy for moderate- to high-complexity renal masses: a propensity-matched study. Int J Urol 31:1366\u0026ndash;1373. https://doi.org/10.1111/iju.15567 \u003c/li\u003e\n\u003cli\u003eMatsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982\u0026ndash;992. https://doi.org/10.1053/j.ajkd.2008.12.034 \u003c/li\u003e\n\u003cli\u003eBellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative Workgroup (2004) Acute renal failure\u0026mdash;definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the Acute Dialysis Quality Initiative (ADQI) group. Crit Care 8:R204. https://doi.org/10.1186/cc2872 \u003c/li\u003e\n\u003cli\u003eKutikov A, Uzzo RG (2009) The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol 182:844\u0026ndash;853. https://doi.org/10.1016/j.juro.2009.05.035 \u003c/li\u003e\n\u003cli\u003eEltzschig HK, Eckle T (2011) Ischemia and reperfusion\u0026mdash;from mechanism to translation. Nat Med 17:1391\u0026ndash;1401. https://doi.org/10.1038/nm.2507 \u003c/li\u003e\n\u003cli\u003eKalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229\u0026ndash;317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7 \u003c/li\u003e\n\u003cli\u003eZager RA, Johnson AC, Becker K (2013) Renal ischemia-reperfusion injury: mechanisms of cellular failure. Transl Res 161:407\u0026ndash;416. https://doi.org/10.1016/j.trsl.2013.01.007 \u003c/li\u003e\n\u003cli\u003eJang HR, Rabb H (2015) The immune response in ischemic acute kidney injury. Nat Rev Nephrol 11:81\u0026ndash;89. https://doi.org/10.1038/nrneph.2014.180 \u003c/li\u003e\n\u003cli\u003eBecker F, Van Poppel H, Hakenberg OW, et al (2009) Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol 56:625\u0026ndash;635. https://doi.org/10.1016/j.eururo.2009.07.016 \u003c/li\u003e\n\u003cli\u003eDirksen MT, Laarman GJ, Simoons ML, Duncker DJGM (2007) Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies. Cardiovasc Res 74:343\u0026ndash;355. https://doi.org/10.1016/j.cardiores.2007.01.014 \u003c/li\u003e\n\u003cli\u003eChatterjee PK (2007) Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review. Naunyn Schmiedebergs Arch Pharmacol 376:1\u0026ndash;43. https://doi.org/10.1007/s00210-007-0183-5 \u003c/li\u003e\n\u003cli\u003eDuke GJ (1999) Renal protective agents: a review. Crit Care Resuscitation 1:265\u0026ndash;275 \u003c/li\u003e\n\u003cli\u003eZarjou A, Sanders PW, Mehta RL, Agarwal A (2012) Enabling innovative translational research in acute kidney injury. Clin Transl Sci 5:93\u0026ndash;101. https://doi.org/10.1111/j.1752-8062.2011.00302.x \u003c/li\u003e\n\u003cli\u003eMurry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124\u0026ndash;1136. https://doi.org/10.1161/01.cir.74.5.1124 \u003c/li\u003e\n\u003cli\u003eWever KE, Warle MC, Wagener FA, van der Hoorn JW, Masereeuw R, van der Vliet JA (2011) Remote ischemic preconditioning by brief hind limb ischemia protects against renal ischemia-reperfusion injury: the role of adenosine. Nephrol Dial Transplant 26:3108\u0026ndash;3117. https://doi.org/10.1093/ndt/gfr103 \u003c/li\u003e\n\u003cli\u003eKharbanda RK, Mortensen UM, White PA, et al (2002) Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106:2881\u0026ndash;2883. https://doi.org/10.1161/01.cir.0000043806.51912.9b \u003c/li\u003e\n\u003cli\u003eChung J, et al (2021) The effect of remote ischemic preconditioning on serum creatinine in patients undergoing partial nephrectomy: a randomized controlled trial. J Clin Med 10:1636. https://doi.org/10.3390/jcm10081636 \u003c/li\u003e\n\u003cli\u003eZager RA, Johnson AC, et al (1984) Responses of the ischemic acute renal failure kidney to additional ischemic events. Kidney Int 26:689\u0026ndash;700. https://doi.org/10.1038/ki.1984.204 \u003c/li\u003e\n\u003cli\u003eOrvieto MA, et al (2007) Ischemia preconditioning does not confer resilience to warm ischemia in a solitary porcine kidney model. Urology 69:984\u0026ndash;987. https://doi.org/10.1016/j.urology.2007.01.100 \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-robotic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jors","sideBox":"Learn more about [Journal of Robotic Surgery](http://link.springer.com/journal/11701)","snPcode":"11701","submissionUrl":"https://submission.nature.com/new-submission/11701/3","title":"Journal of Robotic Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Multiple clamping, robot-assisted partial nephrectomy, renal function, propensity score matching","lastPublishedDoi":"10.21203/rs.3.rs-8153981/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8153981/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo evaluate the effect of clamping multiple renal arteries on postoperative renal function in patients undergoing robot-assisted partial nephrectomy (RAPN).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective review of 694 patients who underwent RAPN for renal tumors between March 2016 and June 2023 was conducted. The patients were categorized into single and multiple clamp cohorts. Baseline differences were minimized using 1:1 propensity score matching. Renal function was evaluated using estimated glomerular filtration rate (eGFR) at 7 days and 1, 3, and 12 months postoperatively. Additionally, acute kidney injury (AKI), chronic kidney disease (CKD) progression, and dialysis requirements were evaluated. Statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAfter matching, 26 patients were included in each group. There were no significant differences in perioperative outcomes, including warm ischemia time, trifecta achievement, and surgical margin status. Despite a longer operative time in the multiple clamp group, no adverse effects on renal function were observed. There were no significant group differences in the eGFR at any time point or in the rates of AKI, CKD progression, or dialysis requirement.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eClamping of multiple renal arteries during RAPN did not appear to negatively affect short- or long-term postoperative renal function. Multiple clamping may be an acceptable technique for achieving a bloodless surgical field when necessary.\u003c/p\u003e","manuscriptTitle":"Effect of multiple renal artery clamping on postoperative renal function in robot-assisted partial nephrectomy: A propensity-matched study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 14:34:57","doi":"10.21203/rs.3.rs-8153981/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-02T21:13:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-02T20:43:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59869173941438528616398900288668250078","date":"2025-11-29T14:42:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-29T01:13:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"284985168225918694568273903341428051427","date":"2025-11-29T01:07:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"202788752322282209914757737378353540514","date":"2025-11-28T12:52:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51668526801941805944504559677085780508","date":"2025-11-28T12:25:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-28T12:01:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-22T12:37:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-22T03:03:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Robotic Surgery","date":"2025-11-19T10:13:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-robotic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jors","sideBox":"Learn more about [Journal of Robotic Surgery](http://link.springer.com/journal/11701)","snPcode":"11701","submissionUrl":"https://submission.nature.com/new-submission/11701/3","title":"Journal of Robotic Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5a7c0e41-6121-4d1d-af24-a4aab736ff7b","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:11:07+00:00","versionOfRecord":{"articleIdentity":"rs-8153981","link":"https://doi.org/10.1007/s11701-025-03115-5","journal":{"identity":"journal-of-robotic-surgery","isVorOnly":false,"title":"Journal of Robotic Surgery"},"publishedOn":"2026-01-05 15:56:55","publishedOnDateReadable":"January 5th, 2026"},"versionCreatedAt":"2025-12-02 14:34:57","video":"","vorDoi":"10.1007/s11701-025-03115-5","vorDoiUrl":"https://doi.org/10.1007/s11701-025-03115-5","workflowStages":[]},"version":"v1","identity":"rs-8153981","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8153981","identity":"rs-8153981","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}