岩見 大基

INTRODUCTION: This study aimed to develop a limited sampling strategy (LSS) and predictive equations to accurately estimate the areas under the concentration-time curves (AUC) of extended-release tacrolimus (TAC-ER) and mycophenolic acid (MPA). METHODS: A retrospective analysis of Japanese kidney transplant recipients yielded 90 TAC-ER AUC0-24 (23 patients) and 80 MPA AUC0-12 (29 patients) datasets, which were randomly split into learning and validation datasets. Training datasets were used to generate the LSS model equations based on multiple linear regression analysis, and the coefficient of determination (R2) was used to assess the goodness of fit of regression models. Validation datasets applied the selected training equations to compute error indices, Passing-Bablok's Kendall's τ, and Bland-Altman limits of agreement, thereby assessing predictive bias, accuracy, and precision. RESULTS AND DISCUSSION: Four equations (C0-C1-C6, C0-C1-C2-C6, C0-C1-C3-C6, C0-C1-C4-C6) showed strong correlations with the actual AUC (R² > 0.95), with the validation identifying C0-C1-C3-C6 as the most reliable for both TAC-ER and MPA. This study demonstrated that LSS using C0-C1-C3-C6 reliably and accurately estimated both the actual TAC-ER AUC0-24 and MPA AUC0-12 simultaneously in kidney transplant recipients. These equations can be feasibly implemented in outpatient clinical settings to reduce time and cost.

INTRODUCTION: Priapism is a persistent penile erection lasting > 4 h without sexual stimulation. Ischemic priapism requires urgent management. We report a recurrent ischemic priapism case post-living-donor kidney transplantation necessitating multiple interventions, including bilateral T-shunt procedures. CASE PRESENTATION: A 44-year-old man with end-stage kidney disease from malignant nephrosclerosis and IgA nephropathy underwent living-donor kidney transplantation. On postoperative Day 5, priapism appeared upon catheter removal. Bedside corporal aspiration was initially performed. Recurrence prompted Winter's shunt on Day 6. Blood gas analysis confirmed ischemic priapism. On Day 7, further recurrence required bilateral T-shunts, resolving the condition. Propofol, used during anesthesia, was suspected as the cause. At the 6-month follow-up, priapism had not recurred, though erectile dysfunction developed. CONCLUSION: This case highlights a rare but serious complication of kidney transplantation under general anesthesia, potentially linked to propofol. Timely escalation from aspiration to surgical shunting is crucial in persistent cases to prevent long-term sequelae.

Tacrolimus-induced chronic nephrotoxicity (TACN) represents a major barrier to long-term graft survival in kidney transplantation, yet its molecular pathogenesis remains incompletely understood. We have previously reported metabolic abnormalities, including carnitine deficiency, nicotinamide adenine dinucleotide depletion, and elevated asymmetric dimethyl arginine (ADMA), in TACN. To identify upstream regulators associated with these metabolic disturbances, we conducted a comprehensive trans-omic analysis, integrating transcriptomics and proteomics of kidney tissues from male ICR mice with TACN (n = 5/group). Differentially expressed genes and proteins were subjected to functional enrichment and transcription factor binding motif analyses, followed by upstream master regulator identification using the Genome Enhancer platform. A total of 785 genes and 2472 proteins were differentially expressed, with partially discordant regulation between transcriptomic and proteomic profiles, underscoring the limitations of single-omic approaches. Upstream analysis identified protein arginine methyltransferase-1 (PRMT1) and integrins, particularly αVβ6, as potential master regulators and therapeutic targets. PRMT1 is implicated in ADMA-mediated nitric oxide inhibition and fibrosis, whereas integrin αVβ6 is associated with tubular injury and renal fibrogenesis. Notably, PRMT1 may activate STAT3, which in turn regulates integrin β6 expression, suggesting a novel PRMT1-STAT3-integrin αVβ6 axis in TACN pathogenesis. This study represents the first trans-omic approach to TACN, providing a foundation for mechanistic validation and therapeutic exploration of PRMT1 and integrins in both preclinical and clinical settings.

OBJECTIVES: We aimed to assess lower urinary tract function and morphological changes in kidney transplant recipients with a history of graft pyelonephritis and investigate the association between specific types of lower urinary tract dysfunction and the risk of recurrent graft pyelonephritis. METHODS: We retrospectively reviewed the medical records of kidney transplant recipients hospitalized for febrile graft pyelonephritis more than 1 year after transplantation between April 2019 and October 2023. Patients underwent cystography and urodynamic studies after infection control and were followed up for at least 12 months. They were classified based on urodynamic findings, and recurrence-free survival was analyzed. RESULTS: Twenty-four patients were included. Vesicoureteral reflux of the grafted kidney was observed in 20 (83.3%) patients. Detrusor overactivity, detrusor underactivity, and low-compliance bladders were diagnosed in 8 (33.3%), 12 (50.0%), and 7 (29.2%) patients, respectively. Based on urodynamic findings, treatment and bladder management were modified in 20 patients. During a median follow-up of 33 months, seven patients developed recurrent graft pyelonephritis. Detrusor overactivity remained an independent risk factor for recurrent graft pyelonephritis (odds ratio, 21.4; p = 0.04). Patients with detrusor overactivity or underactivity but not low-compliance bladder had significantly shorter recurrence-free survival compared with those without these dysfunctions (p = 0.017, 0.038, and 0.38, respectively). CONCLUSIONS: Persistent lower urinary tract dysfunction, particularly detrusor overactivity, is a significant risk factor for recurrent graft pyelonephritis. Comprehensive evaluation of vesicoureteral reflux and lower urinary tract function via urodynamic studies is important to improve posttransplant outcomes in patients with a history of graft pyelonephritis.

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography-tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology.

Objectives: To clarify the need for a kidney exchange program (KEP) in Japan by conducting a questionnaire survey on KEPs and simulated KEPs by virtual cross-matching based on past cases of transplantation avoidance. Methods: In addition to the content regarding KEPs, an electronic survey was conducted to investigate the number of cases of kidney transplant abandonment due to "immunological" reasons over the past 10 years (2012-2021). Virtual cross-matching was conducted to simulate the feasibility of avoiding immunological risks and enabling kidney transplantation in patients who were previously unable to undergo the procedure. Results: The survey received responses from 107 facilities (response rate: 81.7%). In response to the question about the necessity of a KEP in Japan, 71 facilities (66.4%) indicated that KEPs are necessary. In addition, 251 living-donor kidney transplants were abandoned for "immunological" reasons over the past decade (2012-2021). Among the 80 pairs for which detailed information was available, virtual cross-matching simulations showed that 37/80 pairs (46.3%) were donor-specific antibody (DSA)-negative for blood type-matched combinations, and 41/80 pairs (51.3%) were DSA-negative for blood type-incompatible transplants. Conclusions: The need for a KEP in Japan and its potential usefulness were demonstrated.

Immunosuppressants are essential for preventing allograft rejection; however, they require therapeutic drug monitoring to maintain efficacy and to prevent severe complications such as opportunistic infections. Calcineurin inhibitors (CIs) are primarily distributed in red blood cells, whereas mycophenolic acid (MPA) and its metabolites are found in plasma. These differences necessitate separate analyses for each drug, increasing laboratory workload, analytical complexity, and patient burden. We developed a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of CIs such as tacrolimus (Tac), everolimus (Eve), sirolimus (Sir), cyclosporine A (CycA) and MPA in 2.8-µL whole-blood samples, with a hematocrit-based correction to estimate plasma-equivalent MPA concentrations. Performance of this method was assessed by comparison with conventional immunoassay results using linear regression and Bland-Altman analyses, demonstrating excellent agreement, with strong linearity (R2 > 0.995) at <2 to 35 ng/mL for three CIs, 26.0 to 1866 ng/mL for CycA, and 0.1 to 50 μg/mL for MPA. Furthermore, MPA and tacrolimus concentrations closely aligned with routine clinical results (R2 > 0.900), indicating high accuracy and reproducibility. This new approach may be particularly beneficial for hospitalized patients with limited venous access, pediatric populations, and in remote care settings where frequent blood sampling is challenging because of simultaneous quantification and fewer sample volume requirements.

INTRODUCTION: Postrenal transplant urothelial carcinoma necessitates multidisciplinary treatment. We here report the first case of a patient with transplant ureteral and bladder cancer who underwent transplant nephroureterectomy and cystectomy, followed by a second living donor renal transplantation and ileal conduit creation after a cancer recurrence-free period. CASE PRESENTATION: A 78-year-old female with end-stage renal disease who had previously undergone living donor renal transplantation presented with gross hematuria. She was diagnosed with transplant ureteral and bladder cancer and subsequently underwent transplant nephroureterectomy and cystectomy. She was immediately reintroduced to hemodialysis. After a 2-year cancer-free period, a second living donor renal transplantation with simultaneous ileal conduit surgery was successfully performed. Currently, the patient remains cancer-free for 2 years following the second renal transplantation. CONCLUSION: Second renal transplantation and simultaneous ileal conduit creation are alternatives following curative transplant nephrouretero-cystectomy for post-transplant urothelial carcinoma.

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) is a serious issue for long-term graft survival in kidney transplantation. However, the pathophysiology of TAC nephrotoxicity remains unclear. In this study, we analyzed whole blood samples from mice that developed TAC nephrotoxicity in order to discover its mechanism. Mice were divided into a TAC group and a control group (n = 5 per group). The TAC group received TAC subcutaneously (1 mg/kg/day for 28 days), while the control group received normal saline instead. After the administration period, whole blood was collected and metabolomic analysis was performed, revealing significant changes in 56 metabolites. The major metabolic changes were related to uremic toxins, vascular damage, and NAD+. NAD+ levels were significantly lower in the TAC group, and ADP-ribose, nicotinamide, and nicotinamide N-oxide, which are degradation products of NAD+, were significantly higher, suggesting impairment of the NAD+ salvage pathway. NAD+ deficiency suggests cellular aging and mitochondrial dysfunction, which may induce vascular damage and chronic kidney disease. Our study demonstrated a correlation between low NAD+ levels and the pathophysiology of TAC nephrotoxicity.

We report a case of testicular cancer after kidney transplantation in a 29-year-old man. Twenty-two years after the surgery, computed tomography (CT) showed a retroperitoneal mass 3 cm in diameter. Positron emission tomography (PET) -CT revealed high FDG uptake in both the right testis and retroperitoneal mass. Regarding serum tumor markers, α fetoprotein (AFP) was slightly elevated to 12.5 ng/ml. He underwent right radical orchiectomy, and pathological examination revealed pure seminoma. After surgery, the serum AFP level remained high (12. 9 ng/ml), and we initially considered this nonseminoma patient to have a good prognosis according to International Germ Cell Consensus Classification. During three cycles of a combination regimen including bleomycin, etoposide, and cisplatin (BEP), we performed adjustment of immunosuppressive therapy, treatment for Cytomegalovirus infection (valganciclovir hydrochloride), and that for other adverse events associated with systemic chemotherapy. The chemotherapy schedule was delayed, and bleomycin (third course, day 15) was skipped due to adverse effects. After 3 cycles of BEP, the retroperitoneal lymph node metastasis shrunk from 3.0 to 1.5 cm in diameter. In contrast to the good radiological response, the serum AFP level gradually increased during the treatment to 102.6 ng/ml. Therefore, we did not consider the AFP elevation to have derived from residual cancer, and decided to perform close follow-up. During the 3-year follow-up, AFP decreased to around 20 ng/ml, and PET-CT did not show any uptake in the retroperitoneal mass or other sites.

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) has a detrimental effect on long-term kidney graft survival. However, the pathogenesis of TAC nephrotoxicity remains largely unknown. We explored it by focusing on metabolic changes in renal tissues. In this study, mice were separated into TAC and control groups (n = 5/group). TAC was administered to the TAC group (1 mg/kg/d for 28 days) subcutaneously. The control group was similarly treated with normal saline. Renal tissue metabolomes were evaluated. Renal fibrosis was observed only in the TAC group. Metabolomic analysis showed that carnitine and related metabolites were substantially lower in the TAC group than in the control group, presumably due to impaired biosynthesis and reabsorption. Low carnitine levels impair antioxidation in renal tissues and β-oxidation in mitochondria, which may lead to renal tissue damage. This metabolomic analysis revealed that carnitine deficiency in renal tissue appears to explain TAC nephrotoxicity.

INTRODUCTION AND OBJECTIVES: Both computed tomography (CT) and renal scintigraphy (RS) have been used to assess vascular anatomy, renal status, and split renal function (SRF). In this study, we used a recently developed software that facilitates renal volumetric evaluations to compare RS and automated CT volumetry for assessing residual renal function and, thus, estimating postoperative renal function after donor nephrectomy. METHODS: Fifty-one cases of donor nephrectomy were analyzed. Residual renal function was estimated based on RS and CT volumetry. The correlation between the postoperative estimated glomerular filtration rate (eGFR) and expected SRF, measured using RS and three types of CT volumetry data (ellipsoid, thin-slice, and 5-mm slice data), was determined. RESULTS: The correlation coefficient between actual eGFR and expected SRF was significantly associated at each time point and modality (p &lt; 0.0001). At any time point, the difference in correlation coefficient between RS and 5-mm volumetry was significant (p value: 0.003-0.018), whereas the differences in correlation coefficients between RS and the triaxial volume calculation, and the triaxial volume calculation and 5-mm volumetry, were generally statistically insignificant. CONCLUSIONS: Expected SRF was estimated more accurately by CT volumetric calculations (especially 5-mm slice-based volumetry) than RS.

INTRODUCTION: Orthotopic kidney transplantation is an option when heterotopic kidney transplantation into the iliac fossa is inappropriate. We report a case of orthotopic kidney transplantation following stenting of both external iliac arteries to treat arteriosclerosis obliterans. CASE PRESENTATION: A 56-year-old woman on hemodialysis for end-stage kidney disease underwent living-donor kidney transplantation. Desensitization therapy was administered because of her history of sensitization by pregnancy. Stents had been placed previously in both external iliac arteries. The left kidney was removed via an oblique lumbar incision. The two graft arteries were conjoined and anastomosed to the native renal artery end-to-end. The urinary tract was reconstructed by uretero-ureterostomy with ureteral stent placement. Renal function improved promptly after surgery. CONCLUSION: Preoperative imaging of vascular anatomy is important for successful orthotopic kidney transplantation in patients who have previously undergone stenting of both external iliac arteries for arteriosclerosis obliterans.

BACKGROUND: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. METHODS: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. RESULTS: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. CONCLUSIONS: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.

Psoriasis is an immune-mediated chronic inflammatory disease that predominantly affects the skin and joints. Systemic therapies are required for patients with moderate-to-severe psoriasis, and biologics can provide significant symptomatic improvement. Computed tomography (CT) analysis is recommended before and after biologic therapy to exclude the possibility of comorbid infections and malignancies; incidental findings are often detected in asymptomatic patients. In this study, we analyzed the common incidental findings on CT in 227 patients with psoriasis on biologic therapy and 219 living-kidney transplant donors at our hospital. Incidental findings on CT were observed in 176 (77.5%) patients with psoriasis. The most common were fatty liver (82 patients, 36.1%), urolithiasis (54 patients, 23.8%), pulmonary lesions (47 patients, 20.7%), gallstones or postoperative gallstones (38 patients, 16.7%), liver cysts (36 patients, 15.9%), renal cysts (33 patients, 14.5%), and colonic diverticulum (22 patients, 9.7%), which were observed in 38 (17.4%), eight (3.7%), 68 (31.1%), 12 (5.5%), 58 (26.5%), 88 (40.2%), and 10 (4.6%) donors, respectively. The prevalence of fatty liver, urolithiasis, gallstones, and postoperative gallstones was significantly higher in patients with psoriasis. Multivariate logistic regression showed that psoriasis was a risk factor for fatty liver disease, urolithiasis, and gallstones. Currently, incidental findings on CT in patients with psoriasis have not been well studied. The results of this survey will lead to increased awareness of the incidental findings on CT as a complication of psoriasis.

BACKGROUND: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients. METHODS: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. RESULTS: EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). CONCLUSIONS: KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.

BACKGROUND: The left kidney is typically selected for laparoscopic donor nephrectomy. In contrast, right kidney donation raises concerns for donor safety, and venous anastomosis may be difficult to achieve due to the short renal vein. We investigated the safety and operative outcomes of right donor nephrectomy compared with those of the left. METHODS: We retrospectively analyzed the clinical records of living donor-kidney transplant donors and evaluated operative outcomes such as operative time, ischemic time, blood loss, and surgical complications in the donor. RESULTS: We identified 79 donors (left:right = 62:17 cases) between May 2020 and March 2023. There were no significant differences between the 2 groups regarding age, sex, body mass index, and number of renal arteries. Although the operative time (left and right: 190 and 225 minutes, excluding waiting time; P = .009) and warm ischemic time (left and right: 143 and 193 seconds, P = .021) were significantly longer on the right side, the total ischemic time (82 and 86 minutes, P = .463) and blood loss (left and right: 35 and 25 mL, P = .159) were comparable between the groups. There were no significant differences between the groups regarding the surgical complications. CONCLUSIONS: Operative outcomes were similar in both donor sides in the retroperitoneoscopic donor nephrectomies. The right side should be considered for donation in this operative procedure.

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response via the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response via the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA-). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA- patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA- patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8+ and CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation.

Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.

Introduction: We present a case of urothelial carcinoma in a renal allograft successfully treated with pembrolizumab. Case presentation: A 39-year-old woman presented with nausea and anorexia 9 years after a renal transplantation. Positron emission tomography revealed a neoplasm of the renal pelvis of the allograft and multiple lymph nodes with peritoneal metastasis. A diagnosis of a non-muscle-invasive bladder tumor with peritoneal dissemination and jejunal metastasis of urothelial carcinoma was made. After five cycles of gemcitabine and carboplatin, the tumor progressed and pembrolizumab was administered. One week after the first dose, the allograft was rejected, necessitating arterial embolization. After the second cycle, the patient developed Stevens-Johnson syndrome. After discontinuing pembrolizumab, positron emission tomography revealed no increased tumor activity. A complete response was achieved for 21 months without additional treatment. Conclusion: Pembrolizumab was effective in treating urothelial carcinoma of the renal allograft; however, allograft rejection and loss should be considered.

We report a case of bladder cancer in a 54-year-old woman who underwent renal transplantation for chronic renal failure. Six years after the transplantation, she was diagnosed with muscle-invasive bladder cancer with multiple lung metastases. She received gemcitabine/cisplatin therapy for Stage IV bladder cancer, and the dose of the immunosuppressants was reduced to prevent adverse effects. Since lung metastatic lesions disappeared after four courses of chemotherapy and no new lesions were found, we performed radical cystectomy and right nephroureterectomy with ileal conduit construction. Although she was followed closely without therapy, multiple lung metastases appeared 6 months after the radical cystectomy. Gemcitabine/carboplatin therapy was administered, and the lung metastasis improved slightly until the end of the 4th course, but aggressive growth was observed after the 5th course. She switched to palliative treatment without requesting additional treatment and died of cancer 1 year and 9 months after total cystectomy.There is no evidence-based treatment strategy for advanced bladder cancer after kidney transplantation. It is necessary to recognize that the patient had renal dysfunction and was in an immunosuppressed state. Thus, it is crucial to select appropriate drug and surgical treatments for each patient.

Background: A positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood. Cases: In five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor's T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes. Discussion: False-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed. Conclusion: False-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.

Surgical training using live animals such as pigs is one of the best ways of achieving skilled techniques and fostering confidence in preclinical medical students and surgeon trainees. However, due to animal welfare ethics, laboratory animals' usage for training should be kept to a minimum. We have developed a novel kidney organ model utilizing a simple procedure in which the kidney is first refluxed with N-vinyl-2-pyrrolidone (NVP) solution for 1 hour in its bath, followed by permeation for 23 hours, with a subsequent freshwater refluxed for 48 hours in the washing step. Surgical simulation of the prepared kidney model (NVP-fixed kidney) was compared with three types of other basic known simulation models (fresh kidney, freeze-thaw kidney, and FA-fixed kidney) by various evaluations. We found the NVP-fixed kidney to mimicked fresh kidney function the most, pertaining to the hardness, and strength of the renal parenchyma. Moreover, the NVP-fixed kidney demonstrated successful blood-like fluids perfusion and electrocautery. Further, we confirmed that surgical training could be performed under conditions closer to actual clinical practice. Our findings suggest that our model does not only contribute to improving surgical skills but also inspires the utilization of otherwise, discarded inedible livestock organs as models for surgical training.

<title>Abstract</title><sec> <title>Background</title> Simultaneous pancreas and kidney transplantation (SPK) is a treatment option for patients with end-stage renal disease due to type 1 diabetes mellitus. We report a patient with a refractory fistula due to leakage from the duodenal stump of the pancreas graft after an SPK with bladder drainage who was successfully treated with a percutaneous direct injection of <italic>N</italic>-butyl-2-cyanoacrylate (NBCA). </sec><sec> <title>Case presentation</title> A 60-year-old female with a 33-year history of type 1 diabetes mellitus and a 10-year history of renal replacement therapy underwent an SPK in 2015. At the time of transplantation, an abdominal aortic aneurysm with a high risk of rupture was treated by a Y-graft replacement prior to the SPK. Bladder drainage of the pancreas graft was chosen to avoid a vessel graft infection. The patient’s postoperative course was uneventful. The patient was discharged on postoperative day 93 with good-functioning pancreas and kidney grafts. One and a half years after the operation, the patient was found to have acute graft pancreatitis and a leak from the duodenal stump of the pancreas graft due to a paralytic neurogenic bladder. The insertion of an indwelling catheter into the bladder and the endoscopic-guided insertion of a catheter into the graft pancreatic duct through the duodenum/bladder anastomosis did not result in the closure of the fistula. Therefore, NBCA was injected at the site of the leak point using CT-guided technique. The fistula was completely closed immediately after the injection, with no recurrences of leaks. </sec><sec> <title>Conclusions</title> A percutaneous direct injection of NBCA is one of the treatment options to treat intractable fistulas. </sec>

Herein we report the case of a 37-year-old woman with recurrence of lupus nephritis (LN) in a renal allograft during pregnancy. She had developed end-stage renal disease due to LN and was put on hemodialysis at the age of 26 years. She underwent kidney transplantation at the age 28 years. Maintenance immunosuppressants included methylprednisolone, tacrolimus, and mycophenolate mofetil, which were changed to azathioprine when she desired pregnancy. The renal allograft function remained stable and seemingly disease-free until proteinuria and functional decline occurred during the pregnancy (age: 34 years). The baby was delivered by performing a cesarean section at 33 weeks of gestation. Renal allograft biopsy revealed crescent formation. Light microscopy revealed tuft necrosis and endocapillary proliferation. Immunofluorescence microscopy revealed the deposition of immunoglobulin G and C1q. A recurrence of LN (ISN/RPS class IV-G [A/C]) was diagnosed, and the patient was treated with pulse steroid therapy and azathioprine was replaced with mycophenolate mofetil. This treatment improved acute or active lesions of LN and temporarily benefited the renal allograft function. Unfortunately, there were irreversible chronic changes and a gradual decline in the renal allograft function.

OBJECTIVES: To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. METHODS: Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. RESULTS: Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. CONCLUSIONS: The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.

Introduction: After kidney transplantation, patients should be treated with caution and monitored for surgical complications. Among the possible surgical complications, strangulation ileus after kidney transplantation is rare. Case presentation: A 59-year-old woman who had undergone kidney transplantation at 41 years of age presented to our hospital with lower abdominal pain. She was diagnosed with strangulation ileus and underwent emergency surgery. In the lower right abdomen, the small intestine was compressed by cord-like tissue running from the intraperitoneal space to the retroperitoneal space. We confirmed that the cord-like tissue was the ureter of the transplanted kidney. The necrotic small intestine was resected, and ureter-ureteral anastomosis of the ureter of the transplanted kidney was performed. Conclusion: All surgical procedures, including ureteroneocystostomy, require careful attention. The occurrence of some postoperative surgical complications can be prevented by carefully performing the kidney transplantation procedure.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.

PURPOSE: Although transplanting two kidneys from a single donor to two recipients has some advantages, the right and left kidneys are not anatomically identical; thus, a surgical procedure considering the anatomical features of the donor kidneys is needed when transplanting them into the opposite renal fossae. Based on vast experience, the surgical details of pig orthotopic kidney transplantation from one donor to two recipients was reported. METHODS: When the right kidney was transplanted to the left renal fossa, the graft was inverted upside down, not backwards, thus ensuring that the anteroposterior relationship of the renal vessels was maintained and anatomically natural vascular anastomosis could be performed. RESULTS: Using this technique, we could have developed a pig experimental model that is safe and has a high success rate, even for researchers in the middle of their training. This technique of inverting the graft upside down was reported in human kidney transplantation to make vascular anastomosis easier. CONCLUSIONS: In pig orthotopic kidney transplantation from one donor to two recipients, an anatomically natural vascular anastomosis could be performed via inverted grafting when the right kidney was transplanted into the left renal fossa.

Introduction: Femoral nerve palsy is a rare but serious complication of kidney transplantation. We report a case of femoral nerve palsy following kidney transplantation and conduct a review of the literature on this complication. Case presentation: A 35-year-old woman with end-stage kidney disease, underwent kidney transplantation in the right iliac fossa. The day after the transplantation, she could not straighten her right leg. Physical examination revealed a paresis of her right quadriceps muscle. The patient's sensation of her right thigh was also impaired. We diagnosed her with femoral nerve palsy caused by inappropriate compression from a self-retaining retractor. Rehabilitation was started immediately. The patient's motor weakness gradually improved, and the patient became able to walk independently 4 weeks later. However, the patient's neuropathic pain sustained 6 months after her kidney transplantation. Conclusion: The improper use of self-retaining retractors can lead to femoral nerve palsy in patients undergoing kidney transplantation.

Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.