Abstract Background Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are a major cause of antibody-mediated rejection (AMR) after kidney transplantation. Routine pretransplant screening usually focuses on HLA typing and antibodies against HLA-A, -B, -C, -DRB1, and -DQB1. HLA-DPB1 typing is not always included because HLA-DPB1 antigens are expressed at relatively low levels and have historically been considered less immunogenic. However, emerging evidence suggests that anti-HLA-DPB1 antibodies may be sometimes clinically significant. Case presentation A 35-year-old woman with end-stage kidney disease caused by glycogen storage disease type II underwent ABO-compatible(O → A) living kidney transplantation from her mother. Pretransplant immunological evaluation revealed negative complement-dependent cytotoxicity and flow cytometric crossmatch results, and no DSA against HLA-A, -B, -C, -DRB1, or -DQB1 were detected. On postoperative day 2, the patient developed acute pancreatitis. Therapeutic drug monitoring showed trough levels of tacrolimus of 3.5 ng/mL and mycophenolate mofetil of 0.8 μg/mL. Although these levels were within the therapeutic range, drug-induced pancreatitis was suspected on the basis of the clinical course. On postoperative day 4, the patient developed anuria and Doppler ultrasonography demonstrated loss of diastolic blood flow in the transplanted kidney. Despite aggressive fluid resuscitation, graft perfusion did not improve. Graft biopsy could not be performed because cellulitis around the graft region and thrombocytopenia increased the risk of complications. HLA-DPB1 typing and DSA re-evaluation revealed a DSA against HLA-DPw5 (DPB1*05:01) with a normalized mean fluorescence intensity (nMFI) of 10,562. Retrospective analysis of the stored pretransplant serum sample revealed the same antibody with an nMFI of 2,792. Treatment with plasmapheresis and rituximab was initiated, and graft function gradually recovered to creatinine 1.0 mg/dL after approximately 3 weeks of anuria. Conclusions This case suggests that anti-HLA-DP antibodies may be sometimes clinically relevant and could be considered in selected cases, particularly those with a history of pregnancy, blood transfusions or previous transplants, or in cases where unexplained early graft dysfunction is observed.
Background Robot-assisted adrenalectomy (RAA) may overcome some technical limitations of conventional laparoscopy, but its clinical value and the optimal patient selection for RAA remain unclear. The Mayo Adhesive Probability (MAP) score has been shown to predict operative difficulty in urologic surgery, including laparoscopic adrenalectomy (LA), whereas its impact on RAA has not yet been established. Methods We retrospectively reviewed 103 transperitoneal LA cases and 39 RAA cases performed at a single tertiary referral center between April 2010 and December 2025. Baseline characteristics were compared using univariate tests. Predictors of perioperative outcomes were evaluated using univariate and multivariate regression analyses. Results Baseline characteristics were comparable between the two groups. The only significant difference in perioperative outcomes was a shorter length of hospital stay in the RAA group. No conversion to open surgery occurred in either group, and no Clavien-Dindo grade ≥ 3 complications were observed. In the LA group, a MAP score ≥ 3 was independently associated with longer operative time, longer pneumoperitoneum time, and greater estimated blood loss, whereas perirenal fat thickness (PFT) was not an independent predictor. In the RAA group, tumor size was the only independent predictor of operative time, pneumoperitoneum time, robot time and length of hospital stay, whereas neither MAP score nor PFT was associated with perioperative outcomes. Conclusions RAA may reduce the technical burden associated with complex perirenal anatomy. The association between the MAP score and operative difficulty appears to be attenuated in RAA, suggesting that RAA may be a useful surgical option for patients with high MAP scores.
BACKGROUND:Late-onset hypogonadism (LOH), a condition characterized by age-related testosterone decline, is associated with impaired quality of life and adverse clinical outcomes. Although endocrine abnormalities are common in patients undergoing maintenance hemodialysis (MHD), the clinical characteristics and risk factors for LOH in this population remain unclear. This study investigated the prevalence of LOH and its associated clinical factors in male patients on MHD. METHODS:Sixty-nine male patients undergoing MHD were enrolled. LOH was defined as total testosterone ≤250 ng/dL combined with an Aging Male Symptoms Score (AMSS) of ≥27. Clinical features, laboratory parameters, and medication use were compared between patients with and without LOH. Factors associated with LOH were evaluated using multivariate analysis. RESULTS:Fifteen patients (21.7%) met the diagnostic criteria for LOH. Patients with LOH had significantly higher AMSS scores, particularly in the sexual domain. In the revised multivariate analysis excluding variables used in the definition of LOH, statin use remained independently associated with LOH (odds ratio: 8.12, p = 0.017), whereas total cholesterol showed a marginal inverse association (odds ratio: 0.97, p = 0.058). CONCLUSIONS:LOH was observed in approximately 20% of male patients on MHD and was characterized mainly by sexual symptoms. Statin therapy may be associated with LOH; however, the findings should be interpreted cautiously due to potential confounding and limited sample size.
Mid‑regional pro‑adrenomedullin (MR‑proADM), mid‑regional pro‑atrial natriuretic peptide (MR‑proANP), and copeptin are established biomarkers for chronic kidney disease, yet their post‑transplant trajectories and determinants of circulating levels in kidney transplant recipients remain insufficiently characterized. This study investigated temporal changes in these peptides after kidney transplantation and examined their associations with renal function. Twenty‑seven patients undergoing first kidney transplantation were prospectively followed. Plasma MR‑proADM, MR‑proANP, and copeptin levels were measured pre-transplantation and at 7, 30, and 180 days post-transplantation. Correlations between individual peptide and estimated glomerular filtration rate (eGFR) and between peptides were assessed using Spearman's coefficients. Multiple linear regression analyses at post-transplant days 30 and 180 were performed to identify independent determinants of each peptide. All peptides were markedly elevated before transplant and declined significantly after transplant. MR‑proADM showed the most rapid decrease, reaching a nadir by post-transplant day 7, whereas MR‑proANP and copeptin declined more gradually. Across all time points, strong inverse correlation was observed between eGFR and each peptide, with MR‑proADM demonstrating the strongest association (rs=-0.836). Significant positive correlations were observed between peptide pairs. During stable post‑transplant period, MR‑proADM and MR‑proANP remained associated with eGFR, whereas copeptin lost the correlation. Multivariable analyses identified eGFR and BMI as independent determinants of MR‑proADM, eGFR as the sole determinant of MR‑proANP, and BMI as the only determinant of copeptin. All three peptides decline after kidney transplantation accompanying renal function recovery. MR‑proADM is closely related to eGFR and demonstrates early stabilization, suggesting potential usefulness in assessing early graft recovery.
INTRODUCTION:Obesity is a well-recognized risk factor for various systemic disorders and has also been shown to influence perioperative outcomes in surgical fields. In the context of living donor kidney transplantation (LDKT), increased BMI has been associated with greater technical complexity and a higher incidence of postoperative complications, including wound infection and delayed graft function (DGF). We explored the impact of BMI on the perioperative urine volume (UV) and renal function in LDKT. METHODS:We conducted a retrospective analysis at a single institution to assess the impact of BMI on outcomes following LDKT. Patients were stratified according to BMI into the obese group (Og) (BMI ≥ 25 kg/m²) and the non-obese group (nOg) (BMI < 25 kg/m²). Between April 2010 and December 2024, 118 patients underwent LDKT at Oita University Hospital. After excluding patients who experienced acute rejection, underwent repeat kidney transplantation, or developed vesicoureteral anastomotic complications, 109 patients remained eligible for analysis. We compared outcomes and UV within 14 days postoperatively, and renal function between the Og and nOg. The mean (SD) postoperative follow-up period was 79.7(47.2) months in the nOg and 56.1 months (47.5) in the Og (p = 0.0156). RESULTS:A total of 109 patients were analyzed, comprising 36 patients in the Og and 73 in the nOg. Baseline demographic and clinical characteristics were generally comparable between the two groups, including age, sex, comorbidity, donor BMI, duration from dialysis initiation to transplantation, immunosuppressive regimens. However, baseline serum creatinine levels were significantly higher in obese recipients than in non-obese recipients (p = 0.005). Postoperatively, UV on postoperative day 1 (POD 1) was significantly lower in the Og (p = 0.02). Furthermore, the mean rate of creatinine reduction and the mean estimated glomerular filtration rate (eGFR) increase were significantly higher in the nOg from POD1 to POD4 (p<0.05). No significant differences were observed with respect to warm ischemia time (WIT), total ischemia time (TIT), length of hospital stay, or the incidence of postoperative complications. Multivariate analysis identified obesity as an independent predictor of reduced UV on POD1 (p = 0.00978). CONCLUSION:Obese recipients undergoing LDKT demonstrated significantly lower UV on POD1 and a slower initial recovery of graft function. However, these early physiological differences did not translate into a higher incidence of major postoperative complications or prolonged length of hospital stay. These findings suggest that although early UV may be lower in obese recipients, careful and individualized perioperative fluid management is essential to maintain adequate graft perfusion.
Introduction:Clear cell papillary renal cell carcinoma is a distinct histopathological entity first characterized in patients with end-stage renal disease. Although increasingly reported in patients with normal renal function, it remains relatively unfamiliar in routine clinical practice. Case Presentation:A 75-year-old male with normal renal function presented with an incidentally discovered left renal mass. Radiological evaluation revealed a mass with a distinct enhancement pattern. Considering the patient's preference for surgical management, robot-assisted partial nephrectomy was performed, confirming clear cell papillary renal cell carcinoma, with immunohistochemistry demonstrating diffuse cytokeratin 7-positivity, alpha-methylacyl-CoA racemase-negativity, and cup-shaped carbonic anhydrase IX staining. Conclusion:This case demonstrated the characteristic features of clear cell papillary renal cell carcinoma in a patient with normal renal function. Nephron-sparing surgery and rigorous follow-up protocols are crucial management strategies. Future studies with larger cohorts are needed to define the natural history and optimal management of clear cell papillary renal cell carcinoma.
This case report describes a 56-year-old woman with autosomal dominant polycystic kidney disease and chronic renal failure who underwent transcatheter arterial embolization with N-butyl-2-cyanoacrylate-Lipiodol before renal transplantation. Both kidneys were significantly enlarged, necessitating transcatheter arterial embolization to reduce renal volume and create space for transplantation. The right kidney volume decreased from 2520 to 1150 mL within 9 months after transcatheter arterial embolization, enabling successful transplantation. Long-term (37 months) follow-up demonstrated continued shrinkage of the transcatheter arterial embolization-treated right kidney and a spontaneous reduction in the non-transcatheter arterial embolization-treated left kidney. The reduction in renal volume achieved with transcatheter arterial embolization exceeded that reported for conventional methods using metal coils or ethanol. This case highlights the potential of as an effective embolizing agent for patients with autosomal dominant polycystic kidney undergoing renal transplantation.
BK virus (BKV), JC virus, and simian virus 40 (SV40) are polyomaviruses with high genome identity. Therefore, SV40 staining is used for immunostaining to detect polyomaviruses such as BKV. BKV reactivation has been reported to be a risk for high-grade bladder cancer in immunosuppressed kidney transplant patients. We report a kidney transplant patient with SV40 staining-positive muscle invasive bladder cancer. The patient was a 74-year-old woman who received a kidney transplantation in China 17 years prior. After the age of 71 years, decoy cells were detected in urine cytology about once a year, there was no gross hematuria or urinary tract abnormality, and her graft kidney function was stable. However, at the age of 73, urine cytology was suspicious for malignancy, and cystoscopy revealed a bladder tumor. Transurethral resection of the bladder tumor was performed, and pathology revealed high-grade muscle invasive bladder cancer with micropapillary variant and SV40-stained cells in the lesion. Immediate radical cystectomy was performed, and pathology revealed invasive urothelial carcinoma pT3aN0M0 with positive ureteral resection margins. An 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET)-computed tomography (CT) after cystectomy showed peritoneal dissemination not detected by contrast-enhanced CT. A total of four courses of systemic chemotherapy with gemcitabine-cisplatin were administered, but the patient died of cancer 6 months after the diagnosis of bladder cancer. Proactive screening of kidney transplant patients with decoy cells is important because of the possibility of high-grade bladder cancer associated with BKV, even in the absence of hematuria. FDG-PET/CT is useful for accurate staging of high-grade urothelial carcinoma in kidney transplant patients.
ABSTRACT Introduction Metastatic urothelial carcinoma (UC) of the renal pelvis is an aggressive malignancy with a poor prognosis. Although avelumab maintenance therapy is a standard of care for advanced UC, long‐term durable remission after treatment cessation is rare. Case Presentation We report the case of a 71‐year‐old female with metastatic UC of the renal pelvis who achieved a partial response to gemcitabine and cisplatin chemotherapy. She subsequently underwent 40 courses of avelumab maintenance therapy, which she later chose to discontinue. The partial response initially achieved with gemcitabine and cisplatin chemotherapy has been maintained for over 2 years without further intervention following the cessation of avelumab maintenance therapy. Conclusion This case highlights avelumab's potential to induce a profound and durable antitumor immune response, suggesting the possibility of a “functional cure” in a subset of patients. This provides valuable data for guiding clinical decisions on the optimal duration of therapy.
Mid-regional proadrenomedullin (MR-proADM) has been suggested to be a powerful biomarker for the onset, progression, and mortality of various diseases. To achieve sensitive quantification of MR-proADM without cross-reactivity, we established micro-liquid chromatography coupled to the quadrupole time-of-flight mass spectrometry (μLC-QTOF/MS) method using IonKey technology. 100 μL of plasma sample was pretreated by protein precipitation followed by solid-phase extraction. Using the established μLC-QTOF/MS method, plasma MR-proADM concentrations were measured in 198 individuals of the Japanese general population, 13 patients with chronic kidney disease (CKD) stage G3b-G4 (nondialysis), and 12 patients with CKD stage G5 (dialysis). The novel assay fulfilled the requirements of the US Food and Drug Administration guidance for bioanalytical method validation, with a lower limit of quantification of 0.05 ng/mL. Recovery rates from human plasma and matrix effects were 89.6-114.2% and 95.3-111.7%, respectively. Median plasma MR-proADM concentrations were 0.48, 1.16, and 2.75 ng/mL in general population, CKD stage G3b-G4, and CKD stage G5, respectively (p < 0.0001). All measured concentrations were within the calibration range (0.05-100 ng/mL). The robust Passing-Bablok regression plot between MR-proADM concentrations measured by μLC-QTOF/MS and by immunoluminometric assay showed systemic and proportional bias between methods. The values measured by the μLC-QTOF/MS method tended to be lower than those by immunoluminometric assay. An ultrasensitive and selective method using μLC-QTOF/MS for measuring plasma MR-proADM was established. The novel method can be used in the general population and patients and may have better specificity for MR-proADM than the immunoluminometric assay; thus, it may improve the performance of MR-proADM as a biomarker for predicting the prognosis of patients with various diseases.
Objective:To evaluate the clinical significance of a second transurethral resection of the bladder tumour (TURBT) in patients with a primary high-grade (HG) Ta non-muscle invasive bladder cancer (NMIBC), specifically selected for the initial diagnosis. Patients and Methods:We retrospectively analysed 121 patients with primary HG Ta urothelial carcinoma treated at our institution between January 2007 and October 2024. All patients underwent an initial TURBT with the detrusor muscle present in the specimen. Patients were divided into the second TUR group (n = 48) and the non-second TUR group (n = 73). Propensity score matching was performed using age, number of tumours and Bacillus Calmette-Guerin treatment status. Outcomes included the residual tumour rate, recurrence-free survival (RFS), time to progression to muscle invasive bladder cancer (MIBC) and cancer-specific survival (CSS). Results:Residual tumour at the initial resection site was identified in four patients (8.3%) who underwent a second TUR, with two patients (4.2%) being upstaged to T1. The median follow-up was 53 months. There were no significant differences between the two groups in RFS (p = 0.60), time to progression to MIBC (p = 0.63) or CSS (p = 0.18). These findings remained consistent in the matched cohort. Multivariate analysis revealed that a second TUR was not associated with improved RFS. Conclusions:This is the first study to specifically address primary HG Ta bladder cancer, and it suggests that a second TUR may be omitted in selected cases, particularly when the initial resection is complete and the detrusor muscle is adequately sampled. A risk-adapted approach may help reduce unnecessary procedures without compromising oncological safety.
Imbalance between gastrointestinal peptides has been implicated as a cause of chemotherapy-induced nausea and vomiting (CINV) and anorexia in cancer patients. This study comprehensively evaluated the changes in blood levels of five gastrointestinal peptide: substance P, neuropeptide (NPY), motilin, ghrelin and leptin, following chemotherapy, and the relationship between these peptides and CINV or anorexia. This single-center, prospective, observational study recruited 20 patients with esophageal cancer, urothelial cancer, or testiculoma undergoing cisplatin-based chemotherapy. Plasma levels of five gastrointestinal peptides were measured on days 1 (baseline; before administering chemotherapy), 3, 5 and 8 of the chemotherapy session. Anorexia and CINV were defined as visual analog scale scores 25 mm or higher at least once during the observation period. Plasma NPY and leptin were significantly elevated in the early phase (day 3) of the chemotherapy session, while plasma motilin and substance P were significantly elevated in the late phase (days 5 and 8). Plasma motilin showed significant elevation on days 5 and 8 compared to baseline in CINV group but no significant increase in non-CINV group, and the levels were significantly higher in CINV than in non-CINV group. Plasma leptin peaked significantly on day 3 in both anorexia and non-anorexia groups, and remained significantly higher on day 5 compared to baseline in anorexia group but not in non-anorexia group. CINV is associated with excessive secretion of motilin and anorexia is related to sustained elevation of leptin, suggesting the potential of these peptides as quantitative indicators of CINV and anorexia.
Introduction:Cytokine release syndrome is a rare but potentially life-threatening complication of immune checkpoint inhibitor therapy. Its occurrence in renal cell carcinoma treated with combination therapy is less recognized and poses significant management challenges. Case presentation:A 50-year-old male with metastatic renal cell carcinoma developed severe cytokine release syndrome after receiving ipilimumab-nivolumab combination therapy. The patient presented with high fever, fatigue, and elevated inflammatory markers. Early recognition and prompt intervention with tocilizumab led to rapid clinical improvement. Conclusion:This case highlights the importance of increased awareness, prompt recognition, and targeted management of cytokine release syndrome in renal cell carcinoma patients receiving immune checkpoint inhibitor combination therapy. The rapid response to tocilizumab suggests its potential efficacy in managing immune checkpoint inhibitor-induced cytokine release syndrome.
Abstract Organic anion‐transporting polypeptides (OATP)1B are drug transporters mainly expressed in the sinusoidal membrane. Many studies have suggested that OATP1B activity is affected by genetic factor, the uremic toxin 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), and inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Coproporphyrin‐I (CP‐I) is spotlighted as a highly accurate endogenous substrate of OATP1B. We previously reported a positive correlation between plasma CMPF and CP‐I concentrations in patients with chronic kidney disease (CKD). The present study evaluated the impact of genetic polymorphisms, CMPF, IL‐6, TNF‐α, and estimated glomerular filtration rate (eGFR) on individual differences in OATP1B activity in patients with CKD. Seventy‐three patients with CKD who received kidney transplant at least 3 months earlier were analyzed. Plasma CP‐I concentration was higher in OATP1B1*15 carriers than in non‐carriers. In all patients, CP‐I did not correlate significantly with CMPF, IL‐6, TNF‐α, or eGFR. However, when the dataset was cut off at CMPF concentration of 8 and 7 μg/mL, 4 μg/mL, 3 μg/mL or 2 μg/mL, CMPF correlated positively with CP‐I, and correlation coefficient tended to be higher as plasma CMPF concentration was lower. In conclusion, OATP1B1*15 impacted OATP1B activity in patients with CKD, but IL‐6 and TNF‐α did not. However, the impact of CMPF on OATP1B activity was limited to low CMPF concentrations, and the effect could be saturated at high concentrations. When prescribing an OATP1B substrate drug for patients with CKD, the OATP1B1*15 carrier status and plasma CMPF concentration may need to be considered to decide the dose regimen.
Gemcitabine plus cisplatin (GC) is the standard first line of chemotherapy for urothelial carcinoma. However, it is often difficult to complete scheduled GC therapy because of real-world adverse events. Therefore, the reasons behind delays, scheduled cancelations and determined predictive factors for completing scheduled GC therapy were retrospectively analyzed. Patients diagnosed with locally advanced or metastatic urothelial carcinoma from 2009 to 2020 received a 4-week GC therapy schedule in Oita University Hospital. Information was retrospectively extracted from medical records and all cycles were divided into two groups: One wherein all treatments were administered and completed on schedule and the other wherein treatment was either delayed or canceled in during the treatment schedule. Predictive factors were then statistically extracted between the two groups. In total, 70 patients received 201 cycles of a 4-week scheduled GC therapy. Of the 201 cycles, a total of 68 (33.8%) completed all scheduled treatments, while 133 (66.1%) did not complete the treatment as scheduled. In the group where administration was not completed on schedule, the factors of male, ureteral cancer, lower stage, <90% of gemcitabine and cisplatin dosage, solitary kidney, high creatinine level, low estimated glomerular filtration rate level, low platelet count and high alkaline phosphatase level at the initiation of each cycle were more significant. Additionally, the lowest anticancer drug percentage administration was on day 15. From these results, predictive factors for patients with various backgrounds who completed the scheduled 4-week GC therapy based on real-world data were identified. This information can be useful for clinical physicians when deciding the course of treatment.
血液透析用非カフ型カテーテルの日常管理方法は,日本透析医学会,日本麻酔科学会,米国疾病予防管理センターなど国内外のガイドラインが参考になるが,学会により推奨が異なる部分があり,実際の透析施設での運用方法は不明である.今回は各種ガイドラインと実際の透析施設の運用方法の相違を明らかにするため,国立大学医学部附属病院血液浄化部門連絡協議会に参加した42施設の透析担当医師を対象に,カテーテル管理に関するアンケート調査を行った.カテーテル刺入部の管理方法,接続部の管理方法,カテーテルロック方法,留置期間の目安や入れ替え時期など,施設によって管理方法が異なることがわかった.各施設の管理方法を調査することは自施設の管理方法見直しにつながるため重要であり,さらにタスクシフトや医学教育の面からの活用も期待される.また,カテーテル管理方法はエビデンスが不十分な部分もあるので,今後のデータ蓄積が重要である.
Collecting duct carcinoma, also known as Bellini duct cancer, is a rare subtype of renal cell carcinoma with a poor prognosis in the metastatic setting. There are limited data to suggest the efficacy of targeted therapy or immune checkpoint inhibitors for collecting duct carcinoma, except for small series and case reports. Herein, we present the case of a patient with collecting duct carcinoma who exhibited a complete response to pembrolizumab and long-term remission approximately 5 years after drug withdrawal.