Search

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Objective: In December 2021, enfortumab vedotin (EV), an antibody‐drug conjugate directed against nectin‐4, was approved in Japan as a new treatment after platinum‐containing chemotherapy and PD‐1/PD‐L1 inhibitors. This study evaluated, using real‐world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). Materials and methods: Fifty‐five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non‐EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. Results: The median (range) follow‐up period after pembrolizumab discontinuation was 6.3 (0.7–31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non‐EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non‐EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non‐EV group; hazard ratio 0.26; 95% confidence interval 0.16–0.41; p < 0.001) was an independent prognostic factor for OS. Conclusion: EV prolonged OS in mUC following pembrolizumab therapy in real‐world data. [ABSTRACT FROM AUTHOR]

Introduction: The number of facilities adopting intracorporeal urinary diversion (ICUD) using robots instead of extracorporeal urinary diversion (ECUD) is increasing. However, guidance on how to introduce robot‐assisted radical cystectomy (RARC) + ICUD in each urological institute remains unclear. This study aimed to verify the feasibility of the transition from laparoscopic radical cystectomy (LRC) + ECUD to RARC + ICUD. Methods: We retrospectively analyzed 26 consecutive patients who underwent ICUD with an ileal conduit after RARC between 2018 and 2020 (RARC + ICUD early group). We then compared these patients with 26 consecutive patients who underwent ECUD with an ileal conduit after LRC between 2012 and 2019 (LRC + ECUD late group) at Yokohama City University Hospital. Results: In the RARC + ICUD early group compared with the LRC + ECUD late group, the median total operation time was 516 versus 532.5 min (P =.217); time to cystectomy, 191 versus 206.5 min (P =.234); time of urinary diversion with an ileal conduit, 198 versus 220 min (P =.016); postoperative maximum C‐reactive protein levels, 6.98 versus 12.46 mg/L (P =.001); number of days to oral intake, 3 versus 5 days (P =.003); length of hospital stay, 17 versus 32 days (P <.001). The postoperative complication rates (within 90 days) were 23.1% and 42.3% in the RARC + ICUD early and LRC + ECUD late groups, respectively (P =.237). Clavien–Dindo classification ≥3 was noted in 1 and 4 patients in the RARC + ICUD early and LRC + ECUD late groups, respectively (P =.350). Conclusion: Regarding perioperative outcomes, the RARC + ICUD early group was not inferior to the LRC + ECUD late group. This study suggests the feasibility of a transition from LRC + ECUD to RARC + ICUD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the predictive factors for pentafecta achievement of robot‐assisted partial nephrectomy (RAPN) for intermediate highly complex renal tumors (RENAL score ≥ 7). Methods: We retrospectively analyzed the data of 247 patients with renal tumors with a RENAL score ≥ 7 who underwent RAPN. Baseline characteristics and perioperative outcomes were compared between the pentafecta achieved group and the unachieved group. A multivariable logistic regression model was used to identify the predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. Results: Of the 247 patients, 75 (30.3%) patients were in the achieved group and 172 (69.7%) patients were in the unachieved group. The median warm ischemia time and total operation time were 18 min versus 23 min (p < 0.001) and 179 min versus 201 min (p < 0.001) in the achieved and unachieved groups, respectively. In the unachieved group, six patients (3.4%) had major perioperative complications (Clavien–Dindo classification system ≥3). The median preservation rates of estimated GFR at the 1‐year postoperative period were 96.5% versus 83.0% (p < 0.001) in the achieved and unachieved groups. Multivariable logistic regression models revealed that age and tumor size were independent predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. There were no significant differences in cancer‐free survival between the two groups (p = 0.456). Conclusion: Age and tumor size were independent predictive factors for pentafecta achievement, although there was no difference in oncological outcomes between the pentafecta achieved group and the unachieved group in RAPN for cT1 renal tumors with a RENAL score ≥ 7. [ABSTRACT FROM AUTHOR]

Background: The ALSYMPCA trial revealed radium‐223 (Ra‐223) to be a life‐prolonging agent for bone metastatic castration‐resistant prostate cancer (CRPC). However, only 2.8% of enrolled patients in that clinical trial were Asian, and no Japanese patients were enrolled. Several retrospective studies have been published concerning Japanese bone metastatic CRPC patients receiving Ra‐223. However, no study has yet reported the correlation between Ra‐223 induction and the survival in Japanese bone metastatic CRPC patients. This study investigated the effect of Ra‐223 as a life‐prolonging agent in a large Japanese healthcare fee database. Methods: A total of around 410 000 prostate cancer patients were extracted from this database, and 25 934 were diagnosed with CRPC. In these patients, the age, date of the CRPC diagnosis, date of Ra‐223 induction, and prognosis were analyzed. Results: A total of 1628 patients received Ra‐223, and 6693 patients were diagnosed with bone metastasis CRPC, with the remaining 17 613 patients diagnosed with CRPC without bone metastasis. The patients who completed six courses of Ra‐223 showed a significantly more favorable overall and cancer‐specific survival than those who received ≤5 courses (p < 0.0001 and p < 0.0001, respectively). For time from CRPC diagnosis date to death, the Ra‐223 induction group showed a significantly more favorable prognosis with regard to both the overall and cancer‐specific survival than the bone metastatic CRPC patients without Ra‐223 (p < 0.0001 and p < 0.0001, respectively). Conclusions: Bone metastatic CRPC patients who received Ra‐223 showed a significantly better prognosis than bone metastatic CPRC patients who did not receive Ra‐223. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma with Xp11.2 translocation involving the TFE3 gene (TFE3‐RCC) is a recently identified subset of RCC with unique morphology and clinical presentation. The chimeric PRCC‐TFE3 protein produced by Xp11.2 translocation has been shown to transcriptionally activate its downstream target genes that play important roles in carcinogenesis and tumor development of TFE3‐RCC. However, the underlying molecular mechanisms remain poorly understood. Here we show that in TFE3‐RCC cells, PRCC‐TFE3 controls heme oxygenase 1 (HMOX1) expression to confer chemoresistance. Inhibition of HMOX1 sensitized the PRCC‐TFE3 expressing cells to genotoxic reagents. We screened for a novel chlorambucil–polyamide conjugate (Chb) to target PRCC‐TFE3‐dependent transcription, and identified Chb16 as a PRCC‐TFE3‐dependent transcriptional inhibitor of HMOX1 expression. Treatment of the patient‐derived cancer cells with Chb16 exhibited senescence and growth arrest, and increased sensitivity of the TFE3‐RCC cells to the genotoxic reagent etoposide. Thus, our data showed that the TFE3‐RCC cells acquired chemoresistance through HMOX1 expression and that inhibition of HMOX1 by Chb16 may be an effective therapeutic strategy for TFE3‐RCC. [ABSTRACT FROM AUTHOR]

Introduction: Preoperative prediction of surgical difficulty of partial nephrectomy (PN) is essential to minimize the perioperative complications and to achieve a good surgical outcome. Recently, various scoring systems have been used to evaluate the difficulty of PN including R.E.N.A.L (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score. There were no scoring systems evaluating the roughness of the renal tumor surface and we hypothesized that the roughness of the renal tumor surface might affect the surgical difficulty of robot‐assisted partial nephrectomy (RAPN). This study aimed to evaluate the impact of roughness of the renal tumor surface on the surgical outcome of RAPN. Methods: Overall, 161 patients underwent RAPN performed by the same surgeon between May 2016 and April 2019. We divided those tumors into two groups, like "roughness positive (tumor with roughness of tumor surface)" and "roughness negative (tumor without roughness of tumor surface)" according to the roughness of the endophytic region on preoperative computed tomography images. Clinical and pathological outcomes were compared between the two groups. Results: Eighty‐five and 78 tumors were identified roughness negative and positive, respectively. Cases with roughness positive showed a significantly longer operative time, console time, and ischemia time and had greater blood loss than those with roughness negative. Significant and independent predictors of ischemia time and estimated glomerular filtration rate (eGFR) decrease were roughness of tumor surface, tumor size (not for eGFR decrease), and N score of the R.E.N.A.L nephrometry score. Conclusion: Roughness of renal tumor surface was significantly and positively associated with ischemia time and the eGFR decrease rate. [ABSTRACT FROM AUTHOR]

Objectives: To assess the correlation of urine loss rate after catheter removal with long‐term continence after robot‐assisted radical prostatectomy. Methods: We enrolled 163 patients on whom robot‐assisted radical prostatectomy was carried out and whose urine loss rate we were able to evaluate after catheter removal. Urinary incontinence was evaluated from immediately after removal of the catheter to the date of discharge, and at 1, 3, 6 and 12 months after surgery. Urine loss rate was defined as the urine loss volume divided by the total urine volume. Results: The continence rates of patients with ≤1% urine loss rate on the day of catheter removal were 100% at 6 and 12 months after surgery. A multivariate analysis proved that ≤10% urine loss rate on the day of catheter removal was a significant predictor of continence at 3 months after surgery. Furthermore, the continence rate at 12 months of patients who did not achieve ≤10% urine loss rate on the day of catheter removal was 79.5%. Among them, the continence rate at 12 months of patients who achieved ≥15% urine loss rate improvement from the day of catheter removal to the next day was 95.2%; the factor differed significantly between the continence and incontinence groups at 12 months after surgery. Conclusions: The urine loss rate on the day of catheter removal is significantly related to the acquisition of urinary continence. Furthermore, our findings suggest that long‐term urinary continence can be expected, even in the event of poor urine loss rate on the day of catheter removal, if it improves on the next day. [ABSTRACT FROM AUTHOR]

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed. [ABSTRACT FROM AUTHOR]

Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn‐deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF‐κB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn‐deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn‐deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn‐Tfe3‐Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterized by cutaneous and uterine leiomyomatosis with RCC. This disorder is caused by a germline mutation in the fumarate hydratase (FH) gene, which encodes an important enzyme of the tricarboxylic acid (TCA) cycle. This mutation distinguishes HLRCC from sporadic RCCs. Herein, we investigated a case of HLRCC in a 32-year-old man who underwent nephrectomy for treatment of a solid-cystic tumor in the left kidney. Histopathology demonstrated a variegated architecture of papillary, tubulocystic and cribriform patterns composed of high-grade tumor cells with enlarged nuclei and eosinophilic nucleoli. Immunostaining and western blotting revealed no FH expression in the tumor. Genomic DNA sequencing identified a heterozygous mutation involving deletion of the 3' end of exon 2 and intron 2 of the FH gene (c.251_267+7delTGACAGAACGCATGC CAGTAAGTG), and RT-PCR confirmed exon 2 skipping in FH mRNA. The somatic FH gene status of the tumor showed only the mutated allele, indicating loss of heterozygosity as the "second hit" of tumor suppressor gene inactivation. These data support that an FH mutation involving the splice site causes exon skipping, changing the conformation of the protein and accelerating carcinogenic cascades under impaired FH functioning in the TCA cycle. [ABSTRACT FROM AUTHOR]

Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer‐associated gene, VHL, was identified through kindred analysis of von Hippel‐Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia‐inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF‐VEGF/PDGF pathway. Recent whole‐exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer‐associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome ( BHD) is a rare genetic disorder characterized by fibrofolliculomas, pulmonary cysts and renal cell carcinomas ( RCCs). The affected individuals inherit germline mutations in the folliculin gene ( FLCN). We investigated the mutation spectrum and clinicopathologic findings of 312 patients from 120 different families (119 Japanese and 1 Taiwanese). A total of 31 different FLCN sequence variants were identified. The majority were c. 1285dupC ( n = 34), c.1533_1536delGATG ( n = 25), and c.1347_1353dupCCACCCT ( n = 19). Almost all patients presented with pulmonary cysts. The incidence of RCCs in FLCN mutation carriers over the age of 40 was 34.8% (40/115). Fifty-five RCC lesions were surgically resected; most were either chromophobe RCC ( n = 24; 43.6%) or hybrid oncocytic/chromophobe tumors (19; 34.5%). Seventy-six of 156 FLCN mutation carriers (120 probands and 36 sibs, 48.7%) had skin papules; however, cutaneous manifestations were so subtle that only one patient voluntarily consulted dermatologists. Japanese Asian BHD families have three FLCN mutational hotspots. Recurrent episodes of pneumothoraces are the major symptoms suggestive of a BHD diagnosis in our cohort. Characteristic features of lung and kidney lesions may be more informative than fibrofolliculomas as diagnostic criteria for BHD in the Japanese Asian population. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt-Hogg-Dubé syndrome patients. The folliculin gene ( FLCN) that is responsible for Birt-Hogg-Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer. [ABSTRACT FROM AUTHOR]

High serum calcium ( Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone ( PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma ( RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization ( WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset ( n = 683) and/or as of recurrence ( n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival ( OS) and disease-free survival ( DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs. [ABSTRACT FROM AUTHOR]

Background: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. Methods: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1–3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. Results: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group ( P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels ≥0.01 ng/mL showed biochemical failure. Conclusion: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group ( P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy ( P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Artery and vein (AV) clamps can control venous bleeding in the surgical field and prevent carbon dioxide embolism, especially when large veins are expected to open. However, whether AV clamps cause more renal damage than artery‐only (AO) clamps remains unclear. This study aimed to compare renal function and blood loss in surgeries using AO and AV clamps based on high RENAL nephrometry scores (RNS) in robot‐assisted partial nephrectomy (RAPN).We retrospectively analyzed the medical records of 500 patients who underwent RAPN between March 2016 and December 2021. We performed 1:1 propensity matching for these patients.A total of 340 patients with pathological malignancies who were followed up for at least 12 months were included in this analysis. A total of 291 patients with AO clamping and 49 patients with AV clamping were included. Overall, the AV clamp group had higher total RNSs and larger diameters than the AO clamp group. Propensity score‐matched analysis included 37 patients in each clamp group. The median warm ischemia times of the AV and AO clamps were 25 and 22 min, respectively, with no significant difference. There were no statistically significant differences between the groups in the amount of blood loss, rate of acute kidney injury (AKI), or renal function at 1, 3, or 12 months post‐RAPN.Compared with the AO clamp, the AV clamp did not have a detrimental impact on blood loss or renal dysfunction. Consequently, AV clamps may be considered for patients presenting with moderate‐to‐high‐complexity RNSs. [ABSTRACT FROM AUTHOR]