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.