Mitsuru Saito

Background: Obesity is increasingly prevalent among kidney transplant candidates; however, its impact on graft outcomes in Asian populations is not well characterized. We evaluated the association between preoperative obesity and living-donor kidney transplantation outcomes in Japan. Methods: We analyzed 623 living-donor kidney transplants performed from 1998 to 2021 at six centers in northern Japan. Recipients were categorized by body mass index (BMI) at transplant, and multivariable Cox regression was employed for assessing graft outcomes. Results: Obesity (BMI, ≥30 kg/m²; n = 27 [4.3%]) was the strongest graft failure predictor (hazard ratio, 4.62) compared with normal-weight recipients. Moreover, overweight status (BMI, 25–29.9 kg/m²), acute rejection, and older donor age were independent risk factors. Despite similar rejection rates across the BMI groups, recipients with obesity exhibited persistently impaired kidney function from 1-week posttransplant to the 5-year follow-up. Patient survival was comparable across BMI groups; however, underweight status (BMI < 18.5 kg/m²) was associated with higher mortality. Conclusions: Preoperative obesity and overweight status were significant risk factors for graft failure in Japanese living-donor kidney transplant recipients. Meanwhile, the mortality rate was significantly higher in the patients with underweight status at transplant. Pre-transplant weight optimization and shared decision-making with candidates warrant consideration.

The persistent organ shortage has led to the consideration of “marginal” donors, including those of advanced age, but the outcomes of using living kidney donors aged 70 years or older remain debated. This multicenter retrospective cohort study aimed to evaluate the propriety of kidney donation from older adult donors by analyzing the association between transplant outcomes and recipient age. Using data from 633 adult living-donor kidney transplants, we compared an elderly donor group (age ≥ 70 years, n = 75) with a non-elderly donor group (age < 70 years, n = 558). After 1:1 propensity score matching, the elderly donor group showed significantly lower death-censored graft survival. However, this disadvantage disappeared entirely in recipients aged 50 years or older, who exhibited comparable death-censored graft survival to those with non-elderly donors (p = 0.743). In contrast, recipients younger than 50 years who received grafts from elderly donors had markedly inferior death-censored graft survival (p = 0.008). In conclusion, using living kidney donors aged ≥ 70 years is a viable strategy to expand the donor pool, but its success is influenced by recipient age. These results support an age-sensitive approach in counseling and decision-making for kidney transplantation.

Fatty acid-binding protein 4 (FABP4) is an important adipokine associated with inflammatory responses and metabolic regulation. Although a high-fat diet (HF) and/or HF-mediated obesity have been clearly linked to the progression of prostate cancer, with FABP4 potentially playing a critical role in this relationship, the mechanisms by which FABP4 facilitates this interaction remain unclear. After generating FABP4 knockout (FABP4^−/−) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, it was found that FABP4^−/− TRAMP mice presented significantly ameliorated prostate tumorigenesis and tumor progression along with decreased body weight, protumorigenic cytokine secretion, and pan-amino acid synthesis when compared to TRAMP mice under the HF condition. Additionally, treatment with BMS309403—a chemical inhibitor of FABP4—was observed to abrogate the HF-mediated TRAMP tumor progression, along with reductions in body weight and cytokine production. Thus, FABP4 plays an essential role in the progression of HF-mediated prostate cancer through the modulation of metabolic and inflammatory pathways, providing a potential therapeutic target for prostate cancer.

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.

Background Cardiovascular diseases are still highly prevalent after kidney transplantation. However, little is known about the impact of the timing of rejection episodes on cardiovascular disease. The study aimed to analyze the influence of the timing of rejection episodes on cardiovascular events in recipients of living donor kidney transplantation. Methods We studied 572 living donor kidney transplant recipients from the Michinoku Renal Transplant Network (MRTN), which includes 6 centers in the Tohoku region of Japan. Fine-Gray proportional hazards regression analysis with time-dependent variables was used to assess the effect of rejection episode on cardiovascular events. Recipients were divided into three groups: those without rejection (non-rejection, 370 patients), rejection within 6 months after transplantation (early rejection, 99 patients), and rejection after 6 months (late rejection, 103 patients). The effect of timing on cardiovascular events was evaluated using Fine-Gray proportional hazards regression analysis. Results During a median follow-up of 77 months, 70 patients experienced cardiovascular events. Rejection episodes were significantly associated with cardiovascular events (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.26–3.43, P = 0.004), along with age and dialysis vintage. The 5-year cumulative incidence of cardiovascular events was significantly higher in the late rejection group than in the early rejection group (15% vs. 3.3%, P = 0.021). However, no significant difference in 5-year cumulative cardiovascular event incidence was observed between the early rejection and non-rejection groups. Late rejection was significantly associated with cardiovascular events (HR: 2.40, 95% CI: 1.38–4.18, P = 0.002), whereas early rejection was not significantly correlated with cardiovascular event risk (HR: 1.18, P = 0.670). Conclusions Rejections occurring more than 6 months after transplantation is significantly associated with risk of cardiovascular events. Trial registration number 2019-099-1, date of registration; 3 Dec. 2019, retrospectively registered. Graphical Abstract

Single nucleotide polymorphisms (SNPs) reportedly influence the effect of nivolumab in metastatic renal cell carcinoma (mRCC). This study aimed to evaluate the relationship between the clinical outcomes of patients with mRCC and SNPs in programmed cell death protein 1 (PD-1) protein-coding gene (PDCD1) and explore any potential correlation with patient prognosis and incidence of immune-related adverse events (irAEs). In total, 106 patients with mRCC, who were treated with nivolumab alone (n = 59) or nivolumab and ipilimumab (n = 47), were enrolled in the study. Three SNPs in the PDCD1 gene, namely PD-1.3, PD-1.5, and PD-1.6, were assessed. Patients harboring the PD-1.6 G allele experienced more severe (odds ratio, 3.390; 95% confidence interval 1.517–7.756; p = 0.003) and multiple (OR, 2.778; 95% CI, 1.020–6.993 p = 0.031) irAEs than those harboring the AA genotype. Thus, the existence of the PDCD1 PD-1.6 polymorphism (G allele) was associated with the occurrence of severe and multiple irAEs in patients with mRCC. Further evaluation of PDCD1 polymorphisms might help identify patients experiencing irAE by nivolumab treatment.

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

Benign ureteroenteric anastomosis strictures (UESs) are one of many critical complications that may cause irreversible disability following robot-assisted radical cystectomy (RARC). Previous studies have shown that the incidence rates of UES after RARC can reach 25.3%, with RARC having higher UES incidence rates compared to open radical cystectomy. Various known and unknown factors are involved in the occurrence of UES. To minimize the incidence of UES after RARC, our group has standardized the procedure and technique for intracorporeal urinary diversion by applying the following five strategies: (1) wide delicate dissection of the ureter and preservation of the periureteral tissues; (2) gentle handling of the ureter and security of periureteral tissues at the anastomotic site; (3) use of indocyanine green to confirm good blood supply; (4) standardization of the ample ureteral spatulation length for Wallace ureteroenteric anastomosis through objective measurements; and (5) development of an institutional standardized procedure manual. This review focused on the incidence, etiology, prevention, and management of UES after RARC to bring attention to the incidence of this complication while also proposing standardized surgical procedures to minimize its incidence after RARC.

Background: This study assessed the incidence and impact of acute kidney injury (AKI) on renal prognosis in patients who underwent robot‐assisted laparoscopic radical prostatectomy (RARP).Methods: Medical records of 305 patients treated with RARP were retrospectively reviewed. The patients with postoperative AKIs were dichotomized into early AKI (immediately after surgery) and late AKI (1‐7 days after surgery). The impact of AKIs and their risk factors were statistically assessed.Results: Early and late AKI were observed in 143 (46.9%) and 12 (3.9%) patients, respectively. Hypertension and console time were independent risk factors for early AKI. Among the patients with preoperative eGFR ≥60 mL/min, the eGFR decline 12 months after surgery was significantly greater in patients with early AKI than that without early AKI (−6.8 vs −3.2 mL/min, P = .02).Conclusions: Approximately half of patients developed early AKI after RARP. The patients with early AKI had reduced renal function 12 months after surgery.

Less evidence is known about the role of early changes in serum biomarker after androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here we evaluated the impact of pre-treatment prognostic factors and early changes in serum biomarkers on prostate specific antigen (PSA) progression-free and overall survival rates in mHSPC. We retrospectively reviewed the medical records of 60 mHSPC patients (median age 72 years) treated with ADT whose laboratory data at baseline and following 12 weeks were available. Forty-four patients (73%) had PSA progression and 27 patients (45.0%) died during a median follow-up of 34 months. The multivariable Cox hazard model demonstrated that a log-transformed baseline PSA level (p = 0.003) and an extent of bone disease (EOD) score of ≥3 (p = 0.004) were statistically associated with an increased risk for PSA progression whereas one unit increase in a log-transformed PSA change (baseline-12 weeks) was associated with a decreased risk for PSA progression (p = 0.004). For overall survival, a high level of alkaline phosphatase (ALP) at 12 weeks was associated with increased risk (p = 0.030) whereas a one-unit increase in the log-transformed PSA change was associated with decreased risk (p = 0.001). An increased level of PSA at baseline, or an EOD score of ≥3 may be a good predictor of PSA progression, and a high level of ALP at 12 weeks may be a risk predictor of death. A larger decline in PSA at 12 weeks from the baseline was associated with both PSA progression-free and overall survival time. Early changes in serum biomarkers may be useful in predicting poor outcomes in patients with mHSPC who are initially treated with ADT.