Trends in Patient Characteristics on the Japanese Waiting Lists for Deceased-Donor Kidney Transplantation. Are There no Eligibility or Ineligibility Criteria for Registration and Renewal?

BACKGROUND: Controversial issues in registering candidates for deceased-donor kidney transplantation (DDKT) comprise various factors, including age, life expectancy, and dialysis duration. We investigated patient characteristics on the waiting list and discussed suitable criteria in Japan, which has a long waiting period. METHODS: This study included 592 patients on the waiting list for DDKT at our institute between 1982 and 2023. We retrospectively reviewed patients' medical charts and obtained their clinical information. Patient characteristics according to outcomes and eligibility criteria for applying for or renewing registration were investigated. No prisoners were used in the study, and the participants were neither coerced nor paid. RESULTS: Approximately 70%, 45%, and 14.5% of the registered patients were aged >60, >70, and 80 years, respectively. The number of patients aged ≥70 years gradually decreased over time. The median waiting periods of patients who underwent and interrupted DDKT were 13 and 7 years, respectively. Patients in their 70s with a >15-year dialysis period tended to have opportunities for DDKT. Living-donor kidney transplantation was performed in patients aged <60 years. Waiting patients were significantly younger and had a shorter dialysis duration. Advanced age at registration was associated with a significantly high risk of interruption. CONCLUSIONS: Advanced age and longer dialysis periods were considered at registration because patients with these factors tended to experience interruptions despite the long waiting period and high cost. Although older patients can undergo DDKT, factors including surgical cost and risks are considered. Eligibility/ineligibility criteria should be established for DDKT waiting lists in Japan.

Prognostic role of nutritional and inflammatory indicators for patient survival and death with functional graft in living kidney transplant recipients.

BACKGROUND: The clinical importance of nutrition and inflammation in patients with end-stage renal disease is well established. In this study, we investigated the role of nutritional and inflammatory indicators in the patient outcomes of living donor kidney transplant recipients. METHODS: We included 204 consecutive patients who underwent kidney transplantation at our institute between 2003 and 2022. We retrospectively reviewed medical charts to obtain clinical information. Six nutritional indicators and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median patient age and follow-up period were 48 years and 99 months, respectively. The cohort included patients with preoperative malnutrition and microinflammation. No significant differences in graft survival were identified according to nutritional and inflammatory indicators, whereas the survival index, controlled nutritional status, and C-reactive protein levels were associated with patient survival. The survival index was an independent indicator of survival and death in patients with functioning grafts (P = 0.047 and P = 0.013, respectively). Furthermore, the C-reactive protein level could distinguish between low and high mortality risks in patients with good nutrition (P = 0.019). CONCLUSIONS: Our findings suggest that nutrition and inflammation indicators play important roles in predicting outcomes in living donor kidney transplantation recipients. Further research is warranted to establish optimal management strategies.

Follow-up After Donor Nephrectomy in Living Kidney Donors: How to Manage Living Kidney Donors Postoperatively.

BACKGROUND/AIM: This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the optimal management of living kidney donors. PATIENTS AND METHODS: We retrospectively evaluated 180 living kidney donors who underwent donor nephrectomies at our institute. Clinical information was obtained from medical charts, and remnant renal function was defined as the estimated glomerular filtration rate 12 months after donor nephrectomy. RESULTS: Overall, 6/180 donors (3.3%) were lost to follow-up within a year, and the follow-up rate gradually declined yearly. Independent risk factors for loss to follow-up included a follow-up period <60 months and graft survival of the recipient (p=0.002 and p=0.043, respectively). Recipient survival was correlated with loss to follow-up; however, this was not significant (p=0.051). Regarding remnant renal function, age ≥60 years, preoperative estimated glomerular filtration rate <74 ml/min/1.73 m2, and a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73m2 were independent risk factors for poorly preserved remnant renal function (p=0.036, p<0.0001, and p<0.0001, respectively). Using propensity score matching to adjust for preoperative factors, a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73 m2 was the only significant postoperative factor for poorly preserved remnant renal function (p=0.023). CONCLUSION: An increased 5-year follow-up rate could lead to an increase in long-term follow-up, and recipient prognosis may be correlated with the living kidney donor follow-up status. Furthermore, Δsingle-kidney estimated glomerular filtration rate was identified as a factor for establishing the optimal precision follow-up management of living kidney donors.

Difference of oncological efficacy between two immune checkpoint inhibitors following first-line platinum-based chemotherapy in patients with unresectable, metastatic, advanced urothelial carcinoma: a multicenter real-world Japanese cohort.

BACKGROUND: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab. METHODS: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup. RESULTS: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT. CONCLUSIONS: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT.

Pseudoaneurysm after arterial reconstruction in kidney transplant nephrectomy: A case report and literature review.

Background: Pseudoaneurysm formation sometimes complicates transplant nephrectomy. We report a case of bleeding from a pseudoaneurysm after transplantation nephrectomy that resulted in shock and emergency endovascular treatment. Case presentation: A 56-year-old man underwent transplant nephrectomy 3 years and 9 months following transplantation for pyelonephritis-related infection control. On postoperative day 7, he developed sudden pain in the lower abdomen and subsequently went into shock. A pseudoaneurysm at the anastomosis was detected, and urgent endovascular treatment was performed to stem the bleeding. Conclusion: Vascular complications, including pseudoaneurysms, following transplant nephrectomy can be life-threatening, and comprehensive awareness is needed in careful postoperative management.

Risks of infection and severity of coronavirus disease 2019 in kidney transplant recipients: A single-center cohort study.

BACKGROUND: The severity of coronavirus disease 2019 (COVID-19) is known to be high in kidney transplant recipients; however, the risk factors for COVID-19 infection in these patients has not been studied extensively. Therefore, we explored the predictors of COVID-19 infection and severity in kidney transplant recipients in Japan. METHODS: This study included kidney transplant recipients who were regularly followed-up at our hospital from February 2021 to March 2023. We retrospectively reviewed the patients' medical charts; obtained their clinical information, including comorbidities, immunosuppressant usage, and presence of COVID-19 infection; and assessed the risk of COVID-19 infection and severity. Severe illness was defined as a decrease in oxygen saturation. RESULTS: Among the 155 patients, 50 (32.3%) were infected with COVID-19. Multivariate analysis revealed that recipients taking >5 mg of prednisolone or taking tacrolimus instead of cyclosporine were at higher risk of infection (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.01-5.40; OR 2.29, 95% CI 1.03-5.07, respectively). Furthermore, of the 50 infected recipients, 42 had minor illness and eight had severe illness. Multivariate analysis revealed that recipients taking >5 mg of prednisolone were at a higher risk of severity (OR, 11.60, 95% CI 1.19-113.00). CONCLUSION: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection.

Detailed Cause of Donor Ineligibility in Living Donor Kidney Transplants: A Retrospective, Single-Center Cohort Study.

BACKGROUND: Living kidney donors are evaluated to determine their physical and psychological suitability for transplantation and ensure their safety. During this process, we frequently encounter cases where a donor is found to be ineligible. In this study, we surveyed donors who are ineligible for transplantation at our hospital to educate patients, their families, and medical staff regarding transplantation in the future. METHODS: We examined the proportion of ineligible donors among 237 potential donors who visited our hospital between January 2002 and March 2022. Data were collected retrospectively from electronic medical records and evaluated from various aspects such as age, body mass index, medical history, medications, and renal function. RESULTS: The mean age at presentation was 55.5 years, the male-to-female ratio was 1:1.6, and no significant difference was found between the ineligible and eligible donor groups. The transplant ineligibility rate was 23.6%, and the categories were for medical, backout, immunologic, and recipient-related reasons, in descending order. Furthermore, a low glomerular filtration rate (GFR) was the most common cause of medical cases. CONCLUSIONS: Many patients were judged ineligible because of lifestyle-related diseases such as low GFR, diabetes mellitus, and obesity. Therefore, thorough patient education should be conducted using these data as a reference to reduce the number of donors ineligible because of lifestyle-related diseases.

Impact of nutrition and inflammation indicators on peritoneal dialysis initiation and management.

BACKGROUND: The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation. METHODS: A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median age and follow-up period were 65 years and 54 months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD.

Chronological Changes in Emotional Status and Vaccine Implementation Rate Among Patients on the Waiting List for Deceased-Donor Kidney Transplantation During the Prolonged COVID-19 Pandemic.

BACKGROUND: To investigate the emotional attributes and vaccine implementation rate of patients waiting for kidney transplants during the prolonged COVID-19 pandemic. METHODS: We included 145 patients who were on the waiting list at our institution. Clinical information was obtained from medical charts, and emotional changes were assessed using a telephone questionnaire comprising 13 questions, including vaccine implementation. We also investigated factors affecting the decision to accept or decline deceased-donor kidney transplantation during the COVID-19 pandemic. RESULTS: Of the 145 patients, 121 (83.4%) provided informed consent and completed the questionnaire. The median age at registration on the waiting list for deceased-donor kidney transplantation and the median waiting period was 45.5 years and 103 months, respectively. This cohort comprised 84 males and 37 females. Twenty patients (16.5%) were diagnosed with COVID-19, and 15 (12.4%) were more curious about deceased-donor kidney transplantation. One hundred patients (82.6%) were vaccinated against COVID-19 more than thrice. Thirty patients (24.8%) declined, and 91 patients (75.2%) accepted an organ transplant offer during the COVID-19 pandemic. Multivariate analysis revealed that the long-term waiting period (P = .038) and anxiety about COVID-19, such as visiting the transplant facility (P < .0001) and prudence over time (P < .0001), were independent factors influencing the decline of a kidney transplant offer. CONCLUSIONS: Our findings suggest that some patients hesitated to undergo deceased-donor kidney transplantation during the pandemic. There is a need to develop an appropriate system to ensure safe and secure kidney transplantation during prolonged pandemics.

Clinical impact of catheter insertion for peritoneal dialysis on patient survival and catheter-related complications.

OBJECTIVES: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) for catheter insertion is recommended for the systemic introduction of PD and prevention of catheter-related infections. In this study, we investigated patient outcomes in patients who underwent insertion of a PD catheter with a direct method versus the SMAP method. METHODS: We enrolled 295 consecutive patients who underwent PD as a primary renal replacement therapy and underwent insertion of a PD catheter at our institute between 2006 and 2021. We retrospectively reviewed their data and investigated patient outcomes, including mortality and PD catheter-related complications. RESULTS: Median age at PD induction was 65 years in the direct insertion group and 65 years in the SMAP group (P = 0.80). The rate of PD introduction after emergency hemodialysis was significantly higher in the direct insertion group than in the SMAP group (P < 0.001). There was no significant difference in survival between the direct insertion and SMAP groups during the median follow-up period of 54 months (P = 0.12). Additionally, patients who transitioned to hemodialysis or kidney transplantation after PD showed significantly longer survival (P < 0.001). The incidence of PD catheter-related complications was not significantly different between the two groups. A body mass index ≥ 23 kg/m2 was an independent risk factor for peritonitis and exit-site infection (P = 0.006 and P = 0.011, respectively). CONCLUSIONS: Planned sequential renal replacement therapy including hybrid hemodialysis, complete hemodialysis, and kidney transplantation after PD is important for improving patient outcomes. PD catheter insertion by SMAP may not be mandatory in our clinical practice.

Impact of Nocturnal Polyuria and Sleep Quality in Kidney Transplant Recipients With Nocturia.

BACKGROUND: To investigate the quality of life (QOL) of patients with nocturia after kidney transplantation (KT) and the association between nocturnal polyuria and sleep quality. METHODS: In a cross-sectional study, a patient who consented was evaluated using the following items: international prostate symptom QOL score, nocturia-quality of life score, overactive bladder symptom score, Pittsburgh sleep quality index, bladder diary, uroflowmetry, and bioimpedance analysis. Clinical and laboratory data were obtained from medical charts. RESULTS: Forty-three patients were included in the analysis. Approximately 25% of patients urinated once at night, and 58.1% had nocturia twice. Nocturnal polyuria was observed in 86.0% of patients, and overactive bladder was observed in 23.3% of patients. According to the Pittsburgh sleep quality Index, 34.9% of patients had poor sleep quality. Multivariate analysis revealed that patients with nocturnal polyuria tended to have a high estimated glomerular filtration rate (P = .058). On the other hand, multivariate analysis for poor sleep quality revealed that high body fat percentage and low nocturia-quality of life total score were independently correlated factors (P = .008 and P = .012, respectively). Furthermore, the patients with nocturia ≥3/night were significantly older than those with nocturia ≤2/night (P = .022). CONCLUSION: Nocturnal polyuria, poor sleep quality, and aging may decrease the QOL of patients with nocturia after KT. Further investigations, including optimal water intake and interventions, can lead to better management after KT.

A Low Tacrolimus Concentration-to-Dose Ratio Increases Calcineurin Inhibitor Nephrotoxicity and Cytomegalovirus Infection Risks in Kidney Transplant Recipients: A Single-Center Study in Japan.

BACKGROUND: Tacrolimus (TAC) has several problems due to its narrow therapeutic window and variations pharmacokinetics and pharmacodynamics. Recently, several studies reported that TAC metabolism, defined by TAC blood trough concentration to dose (C/D) ratio, was associated with TAC toxicity. Reports on once-daily extended-release TAC (TAC-ER) are limited. The present study aimed to investigate the effect of the TAC metabolic rate on TAC-ER and compare TAC area under the curve (AUC) between fast and slow metabolizers. METHODS: A total of 58 recipients were included in this study. The optimal cut-off value and time of the C/D ratio on TAC-ER for fast and slow metabolizers was determined using receiver operating characteristic curve analysis for biopsy-proven calcineurin inhibitor (CNI) nephrotoxicity. RESULTS: The optimal time to evaluate the C/D ratio was 1 month after kidney transplantation (KT) and the cut-off value was 0.9. The multivariate analysis for CNI nephrotoxicity risk showed that only TAC metabolism was associated with CNI nephrotoxicity (hazard ratio 10.60, P = .005, 95% CI 2.03-55.22). Cytomegalovirus infection occurred more frequently in fast metabolizers when the cut-off value of the C/D ratio was set to 0.9 at 3 months after KT (P = .04). The TAC C4, AUC2-8, was higher in fast metabolizers than in slow metabolizers (P < .01, P = .03, respectively). CONCLUSION: The study revealed that TAC fast metabolizers on TAC-ER may be classified as a high-risk group for CNI nephrotoxicity and cytomegalovirus infection. The result of TAC AUC supported the hypothesis that fast metabolizers tended to be overexposed to immunosuppressive agents early after oral administration.

Clinical significance of limited and extended pelvic lymph node dissection during robot-assisted radical prostatectomy for patients with localized prostate cancer: A retrospective, propensity score matching analysis.

OBJECTIVES: We investigated the diagnostic and therapeutic benefits of limited or extended pelvic lymph node dissection during a robot-assisted radical prostatectomy for localized prostate cancer. METHODS: Diagnostic and therapeutic benefits were assessed according to the rates of pN1 and biochemical recurrence, respectively. The primary outcome was the biochemical recurrence-free rate, and secondary outcomes included the diagnostic and therapeutic benefits of pelvic lymph node dissection. RESULTS: A total of 534 patients were analyzed. Out of the 534 patients, 207 (38.8%) received limited pelvic lymph node dissection while 134 (25.1%) received extended dissection. There were 297 patients with a Briganti index ≥5%. Extended dissections yielded significantly more resected lymph nodes (p < 0.0001), and 72.2% of cases of pN1 were located outside the obturator. The incidence rate of pN1 was 6.1%, and performance of extended lymph node dissection was an independent predictor for pN1 (odds ratio 9.0, 95% confidence interval 2.5-33.1). The rate of biochemical recurrence was 14.9%, and Cox proportional hazards regression analysis of the propensity score matched population revealed that patients with high or very-high risk tended to benefit from limited lymph node dissection (hazard ratio 8.4, 95% confidence interval 0.8-82.3) while the therapeutic benefit of extended dissection was unclear by comparison. CONCLUSIONS: Extended pelvic lymph node dissection significantly improves diagnostic accuracy; however, the therapeutic benefit of pelvic lymph node dissection was not observed in this study.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study.

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30−40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63−22.4) p < 0.0001; HR 3.63 (1.97−6.69), p < 0.0001; HR 2.75 (1.35−5.59), p = 0.0053; and HR 3.17 (1.00−10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02−0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.