Impact of Left Renal Vein Ligation on Renal Function Following En Bloc Resection of Segmental Inferior Vena Cava and Right Kidney.

BACKGROUND: Renal function after left renal vein (LRV) ligation following en bloc resection of segmental inferior vena cava (IVC) and right kidney is understudied. We assessed the impact of LRV ligation on postoperative renal function following en bloc resection of segmental IVC and right kidney. METHODS: We retrospectively reviewed 28 patients who underwent LRV ligation during en bloc resection of segmental IVC and right kidney. Patient demographics, tumor characteristics, intraoperative factors, complications, length of hospital and intensive care unit (ICU) stay, and patient survival were collected. Pre- and postoperative renal function was retrospectively analyzed. RESULTS: Twenty patients underwent robot-assisted surgery and eight patients underwent open surgery. The median operative time was 162 min and estimated blood loss was 350 mL. Ten patients had normal renal function and 12 patients had an initial increase in creatinine but improved gradually. Six patients developed acute renal failure; five patients gradually recovered in 5-32 days after temporary hemodialysis. Renal replacement therapy significantly correlated with maximal anterior-posterior diameter of the LRV (p = 0.001). Complications were observed in 11 cases, four of which were Clavien-Dindo grades I-II. Thirteen patients were alive with no recurrence, nine patients were alive with metastasis, and six cases died during the follow-up period. CONCLUSIONS: LRV ligation following en bloc resection of segmental IVC and right kidney is feasible, with no significant long-term impact on renal function. The maximum anterior-posterior diameter of the LRV is a reliable method for predicting renal replacement therapy in the absence of collateral circulation.

Suitability of the MP1000 Platform for Robot-assisted Prostatectomy: A Prospective Randomised Controlled Trial.

Background and objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP. Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics. Key findings and limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size. Conclusions and clinical implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer. Patient summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery.

CRISPR-Cas9 applications in T cells and adoptive T cell therapies.

T cell immunity is central to contemporary cancer and autoimmune therapies, encompassing immune checkpoint blockade and adoptive T cell therapies. Their diverse characteristics can be reprogrammed by different immune challenges dependent on antigen stimulation levels, metabolic conditions, and the degree of inflammation. T cell-based therapeutic strategies are gaining widespread adoption in oncology and treating inflammatory conditions. Emerging researches reveal that clustered regularly interspaced palindromic repeats-associated protein 9 (CRISPR-Cas9) genome editing has enabled T cells to be more adaptable to specific microenvironments, opening the door to advanced T cell therapies in preclinical and clinical trials. CRISPR-Cas9 can edit both primary T cells and engineered T cells, including CAR-T and TCR-T, in vivo and in vitro to regulate T cell differentiation and activation states. This review first provides a comprehensive summary of the role of CRISPR-Cas9 in T cells and its applications in preclinical and clinical studies for T cell-based therapies. We also explore the application of CRISPR screen high-throughput technology in editing T cells and anticipate the current limitations of CRISPR-Cas9, including off-target effects and delivery challenges, and envisioned improvements in related technologies for disease screening, diagnosis, and treatment.

Transrectal versus transperineal prostate biopsy for cancer detection in patients with gray-zone prostate-specific antigen: a multicenter, real-world study.

Knowledge about the effect of different prostate biopsy approaches on the prostate cancer detection rate (CDR) in patients with gray-zone prostate-specific antigen (PSA) is limited. We performed this study to compare the CDR among patients who underwent different biopsy approaches and had rising PSA levels in the gray zone. Two hundred and twenty-two patients who underwent transrectal prostate biopsy (TRB) and 216 patients who underwent transperineal prostate biopsy (TPB) between June 2016 and September 2022 were reviewed in this study. In addition, 110 patients who received additional targeted biopsies following the systematic TPB were identified. Clinical parameters, including age, PSA derivative, prostate volume (PV), and needle core count, were recorded. The data were fitted via propensity score matching (PSM), adjusting for potential confounders. TPB outperformed TRB in terms of the CDR (49.6% vs 28.3%, P = 0.001). The clinically significant prostate cancer (csPCa) detection rate was not significantly different between TPB and TRB (78.6% vs 68.8%, P = 0.306). In stratified analysis, TPB outperformed TRB in CDR when the age of patients was 65-75 years (59.0% vs 22.0%, P < 0.001), when PV was 25.00-50.00 ml (63.2% vs 28.3%, P < 0.001), and when needle core count was no more than 12 (58.5% vs 31.5%, P = 0.005). The CDR (P = 0.712) and detection rate of csPCa (P = 0.993) did not significantly differ among the systematic, targeted, and combined biopsies. TPB outperformed TRB in CDR for patients with gray-zone PSA. Moreover, performing target biopsy after systematic TPB provided no additional benefits in CDR.

Adding Color to Mass Spectra of Biopolymers: Charge Determination Analysis (CHARDA) Assigns Charge State to Every Ion Peak.

Traditionally, mass spectrometry (MS) output is the ion abundance plotted versus the ionic mass-to-charge ratio m/z. While employing only commercially available equipment, Charge Determination Analysis (CHARDA) adds a third dimension to MS, estimating for individual peaks their charge states z starting from z = 1 and color coding z in m/z spectra. CHARDA combines the analysis of ion signal decay rates in the time-domain data (transients) in Fourier transform (FT) MS with the interrogation of mass defects (fractional mass) of biopolymers. Being applied to individual isotopic peaks in a complex protein tandem (MS/MS) data set, CHARDA aids peptide mass spectra interpretation by facilitating charge-state deconvolution of large ionic species in crowded regions, estimating z even in the absence of an isotopic distribution (e.g., for monoisotopic mass spectra). CHARDA is fast, robust, and consistent with conventional FTMS and FTMS/MS data acquisition procedures. An effective charge-state resolution Rz ≥ 6 is obtained with the potential for further improvements.

A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation.

The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging. This study presents a pseudonatural product targeting IST1-CHMP1B within the ESCRT-III complexes. The compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting, or biogenesis of extracellular vesicles, it rapidly inhibits transferrin receptor recycling in cells, resulting in the accumulation of transferrin in stalled sorting endosomes. Stalled endosomes become decorated by lipidated LC3, suggesting a link between noncanonical LC3 lipidation and inhibition of the IST1-CHMP1B complex.

Assessing the Feasibility and Safety of the Toumai® Robotic System in Urologic Surgery: Initial Experience.

Introduction: Robotic surgery using da Vinci surgical system has gained prominence in urology; emerging robotic platforms are expanding its applications and increasing affordability. We assess the feasibility and safety of a novel system, the Toumai® robotic system in various urological surgeries. Methods: This prospective study was conducted at the first affiliated hospital of Zhengzhou university. Twenty consecutive patients underwent renal and prostatic surgery with the Toumai. The study assessed technical feasibility (conversion rate) and safety (perioperative complications) of the procedures as primary outcomes. Secondary endpoints included key surgical perioperative outcomes: functional and oncologic results. The Endoscopic Surgical System operates within a master-slave protocol, comprising a Surgeon Console, Patient Platform, and Vision Platform. Results: Seventeen patients underwent various nephrectomy procedures and three underwent radical prostatectomy (RP). There was no conversion to alternative surgical approach; a single (Clavien-Dindo grade ≥3b) complication occurred, and no readmission was recorded within 30 days. The median operative time was 120, 140, and 210 minutes for partial nephrectomy (PN), radical nephrectomy, and RP, respectively. Off-clamp PN was performed in one case, and the warm ischemia time in the remaining two case was 18 minutes. The median docking time was 22 minutes for nephrectomy and 20 minutes for RP; no major robotic malfunction was encountered. At 3-month follow-up, no tumor recurrence was recorded, renal function was well preserved, and the continence status was satisfactory. Conclusions: We present the initial clinical utilization of an innovative robotic platform. Complex urological surgeries were successfully completed without conversions and with minimal complications. Further investigations are warranted to confirm these initial findings.

MAEL in human cancers and implications in prognostication and predicting benefit from immunotherapy over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma: a bioinformatic analysis.

Maelstrom (MAEL), a novel cancer/testis-associated gene, may facilitate the initiation and progression of human malignancies, warranting comprehensive investigations. Single-cell and tissue-bulk transcriptomic data demonstrated higher MAEL expression in testis (spermatogonia/spermatocyte), kidney (proximal tubular cell), and brain (neuron/astrocyte), and corresponding cancers, including testicular germ cell tumor, glioma, papillary renal cell carcinoma, and clear cell renal cell carcinoma (ccRCC). Of these cancers, only in ccRCC did MAEL expression exhibit associations with both recurrence-free survival and overall survival. High MAEL expression was associated with an anti-inflammatory tumor immune microenvironment and VEGFR/mTOR activation in ccRCC tissues and high sensitivities to VEGFR/PI3K-AKT-mTOR inhibitors in ccRCC cell lines. Consistent with these, low rather than high MAEL expression indicated remarkable progression-free survival benefits from immune checkpoint inhibitor (ICI)-based immunotherapies over VEGFR/mTOR inhibitors in two large phase III trials (JAVELIN Renal 101 and CheckMate-025). MAEL is a biologically and clinically significant determinant with potential for prognostication after nephrectomy and patient selection for VEGFR/mTOR inhibitors and immunotherapy-based treatments.

Suitability of the MP1000 system for robot-assisted partial nephrectomy: a multicenter randomized controlled noninferiority trial.

PURPOSE: This study aimed to compare the safety and effectiveness of the MP1000 surgical system with the da Vinci Si robot system in robot-assisted partial nephrectomy (RAPN) through a prospective, single-blinded, randomized controlled trial. MATERIALS AND METHODS: A total of 62 patients who were scheduled to undergo RAPN were randomly assigned to either the da Vinci Si robot or MP1000 group. A noninferiority test was conducted with a noninferior intermediate value of 10%. The study compared installation and operation times, estimated blood loss, warm ischemia time, postoperative surgical margin, rate of conversion to open surgery, eGFR level, complications, and other safety indicators between the two groups. RESULTS: All procedures were successfully completed without the need for conversion to open or laparoscopic surgery, and no major complications were observed during the process. The test of noninferiority was achieved. There were no significant differences in median installation time, operation time, complication rate at 3 months, rate of positive surgical margin, and eGFR level at 3 months between the groups. Additionally, no evidence of recurrence was found on imaging in both groups. No difference in National Aeronautics and Space Administration task load index results for ergonomic considerations. A limitation of this study was its small sample size. CONCLUSIONS: The MP1000 system is a suitable platform for RAPN with safety and effectiveness compared with da Vinci Si system.

Ultralight Ultrafast Enzymes.

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it. Bacteria showed faster growth, with most proteins exhibiting higher thermal stability, while for recombinant enzymes expressed in depleted media, faster kinetics was discovered. At room temperature, luciferase, thioredoxin and dihydrofolate reductase and Pfu DNA polymerase showed up to a 250 % increase in activity compared to the native counterparts, with an additional ∼50 % increase at 10 °C. Diminished conformational and vibrational entropy is hypothesized to be the cause of the accelerated kinetics. Ultralight enzymes may find an application where extreme reaction rates are required.

Toward Single Bacterium Proteomics.

Bacteria are orders of magnitude smaller than mammalian cells, and while single cell proteomics (SCP) currently detects and quantifies several thousands of proteins per mammalian cell, it is not clear whether conventional SCP methods will be suitable for bacteria. Here we report on the first successful attempt to detect proteins from individual Escherichia coli bacteria, with validation of our findings by comparison with two bacteria samples and bulk proteomics data. Data are available via ProteomeXchange with the identifier PXD043473.

A three-dimensional renal tumor anatomy and intrarenal relationship nephrometry (ADDD) for robot-assisted partial nephrectomy : 3D-CT based nephrometry for RAPN.

OBJECTIVE: To develop a 3D scoring system of tumor anatomy and intrarenal relationship for assessing surgical complexity and outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We prospectively enrolled patients with a renal tumor who had a 3D model and underwent RAPN between Mar 2019 and Mar 2022. The ADDD nephrometry consisted of the contact surface area between tumor and parenchyma (A), the depth of tumor invasion into the renal parenchyma (D1), the distance from tumor to the main intrarenal artery (D2), and to the collecting system (D3). The primary outcomes included perioperative complication rate and trifecta outcome (WIT ≤ 25 min, negative surgical margins, and no major complications). RESULTS: We enrolled a total of 301 patients. The mean tumor size was 2.93 ± 1.44 cm. There were 104 (34.6%) patients, 119 (39.5%) patients, and 78 (25.9%) patients in the low-, intermediate-, and high-risk groups, respectively. Each point increase in the ADDD score increased the risk of complications [hazard ratio (HR) 1.501]. A lower grade indicated a lower risk of failed trifecta (HR low group 15.103, intermediate group 9.258) and renal function damage (HR low risk 8.320, intermediate risk 3.165) compared to the high-risk group. The AUC of ADDD score and grade were 0.738 and 0.645 for predicting major complications, 0.766 and 0.714 for predicting trifecta outcome, and 0.746 and 0.730 for predicting postoperative renal function reservation. CONCLUSION: The 3D-ADDD scoring system shows the tumor anatomy and its intraparenchymal relationships and has better efficacy in predicting surgical outcomes of RAPN.

m5C-dependent cross-regulation between nuclear reader ALYREF and writer NSUN2 promotes urothelial bladder cancer malignancy through facilitating RABL6/TK1 mRNAs splicing and stabilization.

The significance of 5-methylcytosine (m5C) methylation in human malignancies has become an increasing focus of investigation. Here, we show that m5C regulators including writers, readers and erasers, are predominantly upregulated in urothelial carcinoma of the bladder (UCB) derived from Sun Yat-sen University Cancer Center and The Cancer Genome Atlas cohort. In addition, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) as a methyltransferase and Aly/REF export factor (ALYREF) as a nuclear m5C reader, are frequently coexpressed in UCB. By applying patient-derived organoids model and orthotopic xenograft mice model, we demonstrate that ALYREF enhances proliferation and invasion of UCB cells in an m5C-dependent manner. Integration of tanscriptome-wide RNA bisulphite sequencing (BisSeq), RNA-sequencing (RNA-seq) and RNA Immunoprecipitation (RIP)-seq analysis revealed that ALYREF specifically binds to hypermethylated m5C site in RAB, member RAS oncogene family like 6 (RABL6) and thymidine kinase 1 (TK1) mRNA via its K171 domain. ALYREF controls UCB malignancies through promoting hypermethylated RABL6 and TK1 mRNA for splicing and stabilization. Moreover, ALYREF recognizes hypermethylated m5C site of NSUN2, resulting in NSUN2 upregulation in UCB. Clinically, the patients with high coexpression of ALYREF/RABL6/TK1 axis had the poorest overall survival. Our study unveils an m5C dependent cross-regulation between nuclear reader ALYREF and m5C writer NSUN2 in activation of hypermethylated m5C oncogenic RNA through promoting splicing and maintaining stabilization, consequently leading to tumor progression, which provides profound insights into therapeutic strategy for UCB.

Analysis of Isotopically Depleted Proteins Derived from Escherichia coli and Caenorhabditis elegans Cell Lines by Liquid Chromatography 21 T Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry.

Protein mass measurement by mass spectrometry is complicated by wide isotopic distributions that result from incorporation of heavy isotopes of C, H, N, O, and S, thereby limiting signal-to-noise ratio (SNR) and accurate intact mass determination, particularly for larger proteins [Fenselau et al. Anal. Chem. 1983, 55 (2), 353-356]. Observation of the monoisotopic mass-to-charge ratio (m/z) is the simplest and most accurate way to determine intact protein mass, but as mass increases, the relative abundance of the monoisotopic peak becomes so low that it is often undetectable. Here, we used an isotopically depleted growth medium to culture bacterial cells (Escherichia coli), resulting in isotopically depleted proteins. Isotopically depleted proteins show increased sequence coverage, mass measurement accuracy, and increased S/N of the monoisotopic peak by Fourier transform ion cyclotron resonance mass spectrometry analysis. We then grew Caenorhabditis elegans cells in a medium containing living isotopically depleted E. coli cells, thereby producing the first isotopically depleted eukaryotic proteins. This is the first time isotopic depletion has been implemented for four isotopes (1H, 12C, 14N, and 16O), resulting in the highest degree of depletion ever used for protein analysis and further improving MS analysis.

Laparoscopic placement of left renal vein extravascular stenting in treatment of nutcracker syndrome: Techniques and long-term outcomes.

OBJECTIVES: We aimed to assess the feasibility and efficacy of laparoscopic extravascular stent in treatment of nutcracker syndrome by transperitoneal or retroperitoneal approach. METHODS: Seventy-six patients with nutcracker syndrome were retrospectively enrolled from a tertiary referral center, and underwent transperitoneal (63 patients) or retroperitoneal (13 patients) laparoscopic extravascular stent from March 2011 to December 2020. Surgical parameters, complications, imaging and clinical outcomes were collected and analyzed. RESULTS: All procedures were successfully carried out without open conversion. The median operation time, estimated blood loss, and postoperative hospital day were 120 (interquartile range [IQR]: 90-144) min, 20 (IQR: 10-30) ml, and 7 (IQR: 6-9) days. At a median follow-up of 52 (range: 9-127) months, 60 (79%) patients had complete symptom resolution, 14 (18%) patients had significant symptom improvement, and 2 (3%) patients reported no symptom improvement. Ninety-four percent (50/53) of hematuria, 91% (30/33) of proteinuria, and 89% (25/28) of flank/abdominal pain resolved after extravascular LRV stenting. No significant differences were detected in surgery parameters and recovery rates of clinical symptoms between two approaches (each p > 0.05). However, patients with transperitoneal approach need longer to achieve complete recovery compared with retroperitoneal approach (8.7 vs. 1.5 months, p = 0.016). CONCLUSIONS: Laparoscopic extravascular stent performed either transperitoneally or retroperitoneally is a feasible and effective option in treatment of nutcracker syndrome. Retroperitoneal laparoscopic extravascular stent required shorter time to achieve complete recovery, which should be considered whenever possible in surgical decision-making.

The efficacy of modified binding technique for renorrhaphy during robotic partial nephrectomy: surgical and functional outcomes from single-center experience.

BACKGROUND: To compare the traditional single-layer and double-layer suture renorrhaphy with modified "Binding" suture renorrhaphy (whole rim of the wound was closed by the all-layer flow suture starting from the parenchyma cut edges to hilum, followed by the final defect closure) in robotic partial nephrectomy (RPN) for treating localized renal cell carcinoma in our large institutional experience. METHODS: We retrospectively reviewed clinical data of 406 consecutive patients who underwent RPN from May 2018 and December 2020 in our center. The demographic and oncologic outcome variables were compared between different renal reconstruction groups and the effect of these suture techniques on renal function outcomes was also evaluated. RESULTS: For the single-layer group, median operative time and warm ischemic time were significantly less than that of the double-layer and "Binding" groups (p < 0.001), while the significantly lower eGFR drop (p = 0.014) was also detected within postoperative 3 months from baseline, but this difference lost its statistical significance from 3th month to the last follow-up. The changes in postoperative creatinine values were clinically insignificant among the three groups. In a sub-analysis over 258 patients with moderate/high nephrometry score, those patients who underwent "Binding" suture had an undifferentiated warm ischemic time, estimated blood loss, and length of hospitalization stay with a decreased risk of Grade III complications (postoperative hemorrhage requiring intervention) and improved renal function recovery during the whole follow-up. CONCLUSION: Single-layer suture renorrhaphy may be associated with better renal functional preservation and could prove to be reliable in patients with low-complexity tumor (RENAL score ≤ 6). Patients with moderate/high-complexity tumor (RENAL score ≥ 7) might represent a subgroup of patients having a functional benefit after "Binding" suture renorrhaphy even in the long-term period.

Erythropoietin prevented the decreased expression of aquaporin1-3 in ureteral obstructive kidneys in juvenile rats.

BACKGROUND: Urinary tract obstruction is associated with impaired renal urinary concentration; even after the release of the obstruction, patients still suffer from polyuria. It has been reported that the decreased expression of aquaporins (AQPs) is associated with postobstructive polyuria, and erythropoietin (EPO) can promote the recovery of decreased AQP2 expression induced by bilateral ureteral obstruction. However, whether EPO can promote the recovery of the expression of AQP1-3 after the release of unilateral ureteral obstruction (UUO) has not yet been reported. AIMS: To investigate the effects of EPO treatment on the expression of renal AQP1-3 after the release of UUO. METHODS: UUO was established in rats by 24-h temporary unilateral obstruction of renal ureters. Three days following EPO treatment, the kidneys were removed to determine the expression levels of AQP1-3, NLRP3, caspase-1, and IL-1ß via semiquantitative immunoblotting and immunohistochemistry. RESULTS: EPO inhibited the expression of NLRP3, caspase-1, and IL-1ß; reduced plasma creatinine and urea; and promoted the recovery of AQP1-3 expression in UUO rats. CONCLUSIONS: EPO treatment prevented the decreased expression of renal AQPs and the development of impaired urinary concentration capacity after the release of UUO, which may partially occur by way of anti-inflammasome effects. IMPACT: EPO treatment could prevent the decreased expression of renal water transporter proteins AQP1-3 and the development of impaired renal functions, which may be associated with its anti-inflammasome effects. EPO regulated the expression of renal water transporter proteins AQP1-3, which could provide the potential for the treatment of postobstructive polyuresis. EPO treatment could be one of the effective methods by participating in multiple dimensions for patients with obstructive nephropathy.

Alteration of N6-methyladenosine epitranscriptome profiles in bilateral ureteral obstruction-induced obstructive nephropathy in juvenile rats.

BACKGROUND: Urinary tract obstruction is a common cause of renal failure in children and infants, and the pathophysiological mechanisms of obstructive nephropathy are largely unclear. It has been reported that m6A modulation is involved in renal injury. However, whether m6A RNA modulation is associated with obstructive nephropathy has not yet been reported. The aim of this study was to investigate the m6A epitranscriptome profiles in the kidneys of bilateral ureteral obstruction (BUO) in young rats. METHODS: The total level of m6A in the kidneys was measured by liquid chromatography-tandem mass spectrometry. The mRNAs of related genes were detected by real-time PCR. Methylated RNA immunoprecipitation sequencing was performed to map the epitranscriptome-wide m6A profile. RESULTS: Global m6A levels were increased after BUO, and the mRNA expression levels of m6A methyltransferases and demethylases were significantly decreased in BUO group rat kidneys; the expression levels of EGFR and Brcal were significantly upregulated, while the mRNA expression levels of Notch1 were downregulated (P < 0.05). A total of 154 genes associated with 163 m6A peaks were identified. CONCLUSION: The m6A epitranscriptome was significantly altered in BUO rat kidneys, which is potentially implicated in the pathophysiological processes of obstructive nephropathy. IMPACT: The m6A RNA modification was associated with the process of renal injury in ureteral obstructive nephropathy by participating in multiple dimensions. The dysregulation of m6A methyltransferases and demethylases may be related to the pathophysiological changes of BUO-induced obstructive nephropathy. The m6A RNA modulation of the genes EGFR, Brca1, and Notch1 that were related to the regulation of aquaporin2 might be the potential mechanism for the polyuresis after ureteral obstruction.