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Pregnancy in kidney transplantation (KT) recipients has been challenging because of the high risk of maternal, fetal, and renal complications. Although patients with immunoglobulin A nephropathy (IgAN)-chronic kidney disease (CKD) are at a high risk for hypertension in pregnancy (HIP), the maternal risk in KT recipients with IgAN as the etiology remains unclear. We retrospectively reviewed the medical records of pregnant KT recipients who delivered at our hospital. The incidence of maternal and fetal complications and the impact on kidney allografts between the group with IgAN as the primary kidney disease and the group with other primary diseases were compared. The analysis included 73 pregnancies in 64 KT recipients. The IgAN group had a higher incidence of HIP than the non-IgAN group (69% vs. 40%, p = 0.02). IgAN as primary kidney disease and interval from transplantation to conception were associated with HIP (OR 3.33 [1.11-9.92], p = 0.03, OR 0.83 [0.72-0.96], p < 0.01, respectively). The 20-year graft survival or prevention of CKD stage 5 in group with IgAN was lower than that in the group with other primary disease ( p < 0.01). KT recipients should be informed of the risk of HIP and possibility of long-term worsening of postpartum renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oki, Unagami, Kakogawa, Beppu, Banno, Yagisawa, Kanzawa, Hirai, Omoto, Kitajima, Shirakawa, Hoshino, Takagi and Ishida.)

Objectives: To compare surgical and functional outcomes between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with renal cell carcinoma with stage 4 chronic kidney disease., Methods: This was a retrospective analysis of 60 patients with stage 4 chronic kidney disease (estimated glomerular filtration rate 15-30 ml/min/1.73 m 2 ) who underwent partial nephrectomy for T1 renal cell carcinoma between April 2004 and April 2020. We compared perioperative outcomes according to the surgical approach. Multivariable analysis was performed to identify predictive factors for end-stage renal disease., Results: Robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy were performed in 31 and 29 patients, respectively. The median age was 68 years and 17% of all patients were women. Patient and tumor characteristics did not differ between groups. The operative time (155.2 vs. 221.0 min, p < 0.0001) and the postoperative length of hospital stay (5.2 vs. 10.6 days, p = 0.0083) were significantly shorter, and the estimated blood loss was lower (53.4 vs. 363.2 ml, p = 0.0003) in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group. Preoperative estimated glomerular filtration rate was the only significant predictor of end-stage renal disease after partial nephrectomy on multivariable analysis., Conclusions: Both procedures preserved renal function in this patient cohort, delaying the requirement for postoperative dialysis. Furthermore, robot-assisted laparoscopic partial nephrectomy was associated with shorter operative time and postoperative length of hospital stay, as well as lesser estimated blood loss than open partial nephrectomy., (© 2022 The Japanese Urological Association.)

Pediatric renal transplantation is associated with various surgical complications due to the complexity of the technique and the often-fragile condition of patients with end-stage renal disease. We evaluated the surgical complications associated with renal transplantation via the extraperitoneal approach in pediatric recipients. This retrospective study enrolled 280 patients younger than 16 years old who underwent renal transplantation via the extraperitoneal approach: 216 patients underwent transplant placement in the iliac fossa like in adults, and 64 underwent transplant placement in the distal part of the original renal lower pole (the extraperitoneal cavity). On the basis of the Clavien-Dindo classification, 30 patients (10.7%) showed grade 2 complications and 12 patients (4.3%) showed grade 3 or higher complications. None of the patients showed gastrointestinal complications. In a Cox regression analysis, grade 2 or higher complications were significantly associated with weight less than 15 kg (P = .027) and operative times longer than 245 minutes (P = .029). Among the 49 patients weighing less than 15 kg with an allograft placed in a distal portion of the original renal lower pole, only 3 patients (6.1%) developed surgical complications. Thus, allograft placement in the extraperitoneal cavity can be performed safely in children weighing less than 15 kg., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited., Methods: Patients diagnosed with advanced RCC on maintenance dialysis therapy (ESRD-RCC) and treated with tyrosine kinase inhibitors (TKIs) were retrospectively evaluated. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after initiation of first-line TKI therapy in ESRD-RCC patients were compared to those in RCC arising in the general population (sporadic RCC)., Results: A total of 36 and 240 patients were diagnosed with advanced ESRD-RCC and sporadic RCC, respectively. PFS and OS were significantly shorter in patients with ESRD-RCC than in those with sporadic RCC (p = 0.0004 and p = 0.0045). After adjusting for histopathological type, MSKCC risk and liver metastasis status, ESRD status (ESRD-RCC vs. sporadic RCC) was not an independent risk factor for PFS or OS (both, p > 0.05). The ORR tended to be lower in patients with ESRD-RCC than in those with sporadic RCC (11% vs. 28%, p = 0.0833). In 34 patients with ESRD-RCC treated with sorafenib, longer duration of dialysis was an independent prognostic factor for shorter OS (hazard ratio 3.21, p = 0.0370)., Conclusions: Outcome of advanced ESRD-RCC was poorer than that of sporadic RCC, but this finding was affected by other prognostic factors. Nevertheless, the study suggested that advanced ESRD-RCC was not an indolent disease. Additionally, patients with a longer duration of dialysis therapy might require careful monitoring.

Background: The aspartate transaminase (AST)/alanine transaminase (ALT) ratio (ie, the De Ritis ratio) is associated with prognosis in some types of cancers including renal cell carcinoma (RCC). Meanwhile, an effective prognosticator for end-stage renal disease (ESRD)-associated RCC remains unknown. Thus, we investigated the prognostic impact of the AST/ALT ratio in patients with ESRD-associated RCC., Patients and Methods: We retrospectively evaluated 243 patients receiving radical nephrectomy for nonmetastatic ESRD-associated RCC. The patients were divided according to the cutoff value of preoperative AST/ALT ratio. Prognostic factors associated with cancer-specific survival (CSS) after radical nephrectomy were analyzed., Results: The maximum Youden index showed that the cutoff value of the AST/ALT ratio was 1.42. The high AST/ALT ratio group (≥ 1.42; n = 88) had a significantly shorter 10-year CSS than the low AST/ALT ratio group (64.3% vs. 87.2%; P = .0027). Multivariate analysis revealed that the AST/ALT ratio was an independent prognostic factor of CSS (hazard ratio [HR], 3.03; P = .0020), together with serum C-reactive protein level (HR, 4.84; P < .0001), pathologic stage (HR, 2.79; P = .0030), and tumor grade (HR, 7.08; P = .0087). Based on these independent factors, the patients were further classified into 3 groups: low (0-1 factor), intermediate (2 factors), and high risk (3-4 factors). The 10-year CSS in the high-risk group was significantly shorter than that of the other groups (68.9% vs. 70.9% vs. 94.4%; P < .0001)., Conclusion: The AST/ALT ratio can aid in the risk classification of patients with ESRD-associated RCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73 m 2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation., (© 2020 Wiley Periodicals, Inc.)

Background: A higher prevalence of bladder cancer is reported in solid organ recipients, and advanced cancer requires radical cystectomy combined with urinary diversion. Surgery is technically challenging in kidney transplant recipients because of urinary tract abnormalities. Here, we describe the use of a robot-assisted approach in a kidney transplant recipient., Case Presentation: The etiology of the patient's end-stage renal disease was bilateral hypoplastic kidney. The patient started to receive hemodialysis at 19 years of age and underwent living-related kidney transplant at 23 years of age. Thirteen years later, he was diagnosed with invasive urothelial carcinoma and underwent robot-assisted radical cystectomy with extracorporeal neobladder construction under open laparotomy. Surgery was indicated to enhance suture flexibility and dissection of the peribladder tissues. Although the patient had an intraperitoneal infection caused by leakage from the vesicourethral anastomosis site and required drainage of the abscess, his condition stabilized after antibiotic treatment., Conclusion: This case outlines the effectiveness of the robot-assisted approach in patients with urinary tract abnormalities, such as kidney transplant recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Previous studies have demonstrated an association between low serum creatinine levels and adverse outcomes in patients undergoing maintenance hemodialysis. However, little is known regarding whether long-term changes in serum creatinine predict outcomes independently and incrementally over a single point evaluation., Methods: Serum creatinine data at index (June 2013) and for the 18 months prior to the index blood sampling (between January 2012 and June 2013) were evaluated in 346 hemodialysis patients. Patients were followed from the index blood sampling for primary (all-cause mortality) and secondary (cardiovascular death) endpoints., Findings: During a median follow-up of 5.7 years, there were 82 all-cause and 25 cardiovascular deaths. Compared to patients who survived, those who died displayed a greater time-dependent reduction in creatinine levels during the 18 months prior to the index assessment, coupled with a greater decrease in predialysis body weight (interaction p = 0.007). Patients who displayed creatinine decline over the prior 18 months (∆ creatinine<0 mg/dL) had higher all-cause mortality than those who maintained creatinine levels (∆ creatinine≥0 mg/dL). After adjustment for clinical factors and baseline creatinine index, antecedent creatinine decrease was independently associated with an increased risk of all-cause mortality, with an incremental prognostic value over baseline creatinine index alone. A reduction in creatinine levels was also associated with cardiovascular death independent of the baseline creatinine index., Discussion: A long-term antecedent decrease in serum creatinine levels is independently associated with clinical outcomes in hemodialysis patients, with an incremental prognostic value over baseline creatinine index alone. Our data suggest that serial creatinine measurements are a useful prognosticator in practice., (© 2019 International Society for Hemodialysis.)

Objectives: To investigate the cumulative return-to-work (RTW) rate and to identify predictors of employment after kidney transplantation (KT)., Design: Retrospective, outpatient-based cohort study., Setting: This was a single-centre study of the largest Japanese kidney transplant centre., Participants: We selected Japanese kidney transplant recipients aged 20-64 years who were employed in paid jobs at the time of transplantation and who visited an outpatient clinic from December 2017 to March 2018. From 797 patients, we evaluated 515 in this study., Interventions: We interviewed patients at an outpatient clinic and investigated the timing and predictors of RTW using logistic regression models., Primary and Secondary Outcome Measures: The primary outcome was the cumulative RTW rate, and the secondary outcome was to investigate the predictors of RTW after KT., Results: Among the 515 included recipients, the cumulative overall partial/full RTW rates at 2, 4, 6 and 12 months were 22.3%, 59.0%, 77.1% and 85.0%, respectively. The median duration from transplantation to RTW was 4 months. Regarding partial/full RTW, according to the multivariable analysis including all variables, male sex was a greater predictor for RTW than female sex (OR 2.05, 95% CI 1.32 to 3.20), and a managerial position was a greater predictor than a non-managerial position (OR 2.23, 95% CI 1.42 to 3.52). Regarding full RTW, male sex (OR 1.95, 95% CI 1.25 to 3.06) and managerial position (OR 1.95, 95% CI 1.25 to 3.06) were also good predictors., Conclusions: The cumulative RTW rate was 85.0% 1-year post-transplantation. Given that cumulative RTW rates varied by sex and position, transplant and occupational physicians should support kidney transplant recipients in the aspect of returning to work., Trial Registration Number: UMIN000033449., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

ABO-incompatible kidney transplantation (ABO-ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO-compatible kidney transplantation (ABO-CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO-ILKTs and ABO-CLKTs at 2 years post-transplantation. We included 65 ABO-ILKTs and 94 ABO-CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO-CLKT and ABO-ILKT. The hospitalization costs for ABO-CLKT and ABO-ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2-year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO-CLKT and ABO-ILKT, respectively, indicating that the medical costs of ABO-ILKT recipients were non-significantly higher than those of ABO-CLKT recipients at 2 years post-transplantation (P = 0.0866). ABO-ILKT and ABO-CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post-transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO-ILKT group than in the ABO-CLKT group. ABO-ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO-CLKT not only in terms of outcomes but also in terms of medical cost., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The safety of kidney transplantation (KT) for end-stage kidney disease (ESKD) after haematopoietic stem cell transplantation (HSCT) for haematological disease has not been investigated thoroughly., Methods: In this retrospective multicentre study, we investigated the clinical courses of six ESKD patients that received KT after HSCT for various haematological diseases. Data for six such patients were obtained from three institutions in our consortium., Results: Two patients with chronic myeloid leukaemia, one with refractory aplastic anaemia and another one with acute lymphocytic leukaemia received bone marrow transplantation. One patients with acute lymphocytic leukaemia received umbilical cord blood transplantation, and one with mantle cell lymphoma received peripheral blood stem cell transplantation. The patients developed ESKD at a median of 133 months after HSCT. Two patients who received KT and HSCT from the same donor were temporarily treated with immunosuppressive drugs. The other patients received KT and HSCT from different donors and were treated with antibody induction using our standard regimens. For one patient with ABO-incompatible transplantation, we added rituximab, splenectomy, and plasmapheresis. In the observational period at a median of 51 months after KT, only one patient experienced acute T-cell-mediated rejection. Four patients underwent hospitalization because of infection and fully recovered. No patient experienced recurrence of their original haematological disease. All patients survived throughout the observational periods, and graft functions were preserved., Conclusions: Despite the high infection frequency, survival rates and graft functions were extremely good in patients compared with previous studies. Therefore, current management contributed to favourable outcomes of these patients.

Background: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS., Methods: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment., Results: As expected, subjects in the high IS group (IS ≥ 33.8 μg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 μg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups., Conclusions: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 μmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 μmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients., (© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Patients with Alport syndrome (AS) develop progressive kidney dysfunction due to a hereditary type IV collagen deficiency. Survival of the kidney allograft in patients with AS is reportedly excellent because AS does not recur. However, several studies have implied that the type IV collagen in the GBM originates from podocytes recruited from the recipient's bone marrow-derived cells, suggesting the possibility of AS recurrence. Limited data are available regarding AS recurrence and graft survival in the Japanese population; the vast majority were obtained from living related kidney transplantation (LRKTx)., Methods: In this retrospective study, twenty-one patients with AS were compared with 41 matched patients without AS from 1984 to 2015 at two centers using propensity scores. Nineteen of the 21 patients with AS underwent LRKTx. The mean post-transplant follow-up period was 83 months in the AS group and 110 months in the control group. Histopathological AS recurrence was assessed by immunoreactivity of α5 (type IV collagen) antibody and electron microscopy., Results: The graft survival rate was equivalent between patients with and without AS (86.7% vs. 77.1% and 69.3% vs. 64.2% at 5 and 10 years; p = 0.16, log-rank test). Immunoreactivity to α5 antibody showed strong linear positivity with no focal defect in six patients. Electron microscopy showed no GBM abnormalities in two patients who were exhibiting long-term kidney allograft survival., Conclusions: We confirmed that α5 and the GBM structure were histopathologically maintained in the long term after kidney transplantation. The patient and graft survival rates were equivalent between Japanese patients with and without AS.

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics., (© 2018 S. Karger AG, Basel.)

Objective: To compare transplant outcomes among elderly (aged ≥60 years) and non-elderly recipients, and to evaluate the acceptability of elderly living donor kidney transplantation in practice after consideration of living donor type., Methods: We included 830 adult patients with living donor kidney transplantation between 2000 and 2011 in this retrospective cohort study. We compared death-censored graft survival, patient survival, biopsy-proven rejection, complications, and renal function in elderly (n = 119) and non-elderly recipients (n = 278)., Results: There was no significant difference in 10-year death-censored graft survival (P = 0.980). Corresponding patient survival rates in the elderly and non-elderly groups were 84.1% and 98.1%, respectively (hazard ratio 6.15, 95% confidence interval 2.12-17.82, P < 0.001). Elderly patients had more complications and chronic T-cell-mediated rejection. Factors associated with death in elderly recipients with functioning grafts were residual advanced recipient age (hazard ratio 1.39), decreased hemoglobin (hazard ratio 4.10), hepatitis B virus (hazard ratio 7.89), hepatitis C virus (hazard ratio 13.12) and elevated alanine aminotransferase (hazard ratio 1.13)., Conclusions: Elderly living donor kidney transplantation seems to provide adequate acceptable outcomes. However, physicians should be cautious when evaluating elderly patients with hepatitis, and further studies are required to improve long-term outcomes., (© 2017 The Japanese Urological Association.)

Background: IgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49-83 % of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5-60 %, leading to graft loss in 0-50 % of these patients. However, limited data are available on recurrence and graft loss after renal transplantation., Methods: We evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women's Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121 ± 69 months for IgA vasculitis and 147 ± 66 months for the controls., Results: The 15-year patient survival was 100 % in IgA vasculitis and 97.6 % in the controls (p = 0.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81 % in IgA vasculitis and 100, 90.5, and 88.1 % in the controls, respectively (p = 0.63). The recurrence rate was 28.6 % (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft., Conclusion: The long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6 %, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis.

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Background: Left ventricular ejection fraction (LVEF) is a predictor of adverse outcomes in hemodialysis patients. LVEF is, however, an integral parameter determined by contractility, loading condition, and coupling. We sought to determine whether these components would better predict adverse outcomes and have incremental prognostic value over a validated clinical score and EF., Methods: Two hundred thirty-four hemodialysis patients were prospectively followed up for primary composite endpoint: all-cause death, nonfatal myocardial infarction, and hospitalization due to worsening heart failure (HF). Load-independent contractility (end-systolic elastance [Ees] and preload recruitable stroke work [PRSW]) and arterial afterload (arterial elastance [Ea]) were noninvasively estimated. Ventricular-arterial coupling was assessed using the Ea/Ees ratio. LV global longitudinal strain (GLS) and mitral E-wave over annular velocity E' ratio (E/E') were also measured., Results: During a median follow-up of 776 days, 30 patients developed the primary endpoint. Ees, PRSW, GLS, S', Ea/Ees, E/E', and EF were independently associated with the outcome after adjusting for the clinical score and prior HF hospitalization, whereas end-diastolic volume index or arterial afterload parameters were not. The nested Cox models indicated that Ea/Ees had independent and incremental predictive value over the model based on the score and either EF or E/E'. Furthermore, Ea/Ees continued to have predictive value after adjusting for GLS. The classification and regression analysis stratified event rates ranging from 4.2% to 68.8%., Conclusions: LV contractility and Ea/Ees were independently associated with adverse outcome in hemodialysis patients. Ea/Ees had an incremental prognostic value over the clinical score and EF., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

We compared the clinical features, pathological features, and prognoses of patients with renal cell carcinoma (RCC) arising in the native kidney after kidney transplantation (RCC-transplant) or on hemodialysis (RCC-HD), and analyzed predictive factors for survival at a Japanese single institution. This cohort included 42 patients in the RCC-transplant group and 467 patients in the RCC-HD group. RCC-transplant patients were younger (53 years vs. 56 years, P = 0.0358) and had less frequent symptoms (12% vs. 27%, P = 0.0344) than RCC-HD patients. Although tumor size, tumor stage, and histological subtype were not significantly different, the RCC-transplant group had less frequent multifocal occurrences and ACDK. Overall 5-year survival (RCC-transplant, 80%; RCC-hemodialysis, 76%; P = 0.3217) and 5-year cancer-specific survival (CSS; RCC-transplant, 84%; RCC-hemodialysis, 89%; P = 0.8916) were not significantly different between the two groups. Tumor stage and grade were significant predictors for CSS. Although kidney transplantation and hemodialysis were not associated with CSS, tumor stage was an independent predictor of CSS., (© 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Unlabelled: End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 [sST2], galectin-3 [Gal-3]), and uremic toxicity (indoxyl sulfate). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients and have incremental prognostic value over the clinical score and NT-proBNP level., Methods: A total of 423 hemodialysis patients were prospectively followed up for primary (all-cause death) and secondary end points (a composite of all-cause death or cerebrocardiovascular events)., Results: During a mean follow-up of 2.1 ± 0.4 years, there were 48 all-cause deaths and 78 composite outcomes. Soluble isoforms of ST2, Gal-3, and NT-proBNP were associated with all-cause deaths but indoxyl sulfate was not in both log-rank test and receiver operating characteristic analysis. Both sST2 and Gal-3 had independent and incremental prognostic value for both outcomes over the AROii score and NT-proBNP. Although adding sST2 did not reclassify over the model-based AROii score and NT-proBNP for all-cause death, further addition of Gal-3 did. Subgroup analyses of patients with left ventricular ejection fraction measurement (n = 301) corroborated these results, where the 2 biomarkers remained independent and incremental for both all-cause death and composite outcome after adjusting for the risk score and the ejection fraction., Conclusions: Both sST2 and Gal-3 had independent and incremental prognostic values over NT-proBNP and an established risk score in patients with hemodialysis. Assessment of sST2 and Gal-3 further enhances risk stratification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells., (© 2016 Asian Pacific Society of Nephrology.)

Incidental hemodialysis-related renal cell carcinoma (id-RCC) has been reported to have a good prognosis. However, we have observed rapid progression of id-RCC in some renal transplant patients. Operative indications for id-RCC detected via computed tomography (CT) immediately before renal transplantation (RTx) remain unclear. The purpose of this study was to examine the effects of immunosuppression on the progression of solid-type RCC (s-RCC) and cystic-type RCC (c-RCC). We divided 202 patients with id-RCC into four groups as follows: Group 1, s-RCC with RTx (n = 17); Group 2, c-RCC with RTx (n = 27); Group 3, s-RCC without RTx (n = 53); and Group 4, c-RCC without RTx (n = 105). Five-year cancer specific survival (CSS) rates were significantly worse in Group 1 than Group 3 (79.6% and 100%, respectively, P = 0.012), as were non-recurrence rates (NRRs) (59.2 and 100%, respectively, P < 0.001). In contrast, 5-year CSS rates were similar in Group 2 and Group 4 (100% and 95.7%, respectively, P = 0.295) as were NRR (100% and 98.7%, respectively, P = 0.230). Solid-type RCC should be removed immediately after RTx, and more carefully monitored for recurrence during follow-up., (© 2015 Steunstichting ESOT.)

Background: Although cardiovascular events in hemodialysis (HD) patients are the most frequent on the day after a long (2 days) interdialytic interval (IDT), it has been uncertain whether accumulation or elimination of large extracellular fluid volume, electrolyte, and/or uremic substances is the culprit for this. We sought to test our hypothesis that the long IDT alters echocardiographic parameters at rest and during exercise in stable maintenance HD patients compared with other IDTs., Methods: We performed a cross-sectional comparison using 1-way repeated analysis of variance or Friedman test of echocardiograms at 3 different IDTs, just after HD, after short IDT (1 day), and after long IDT, among 80 stable Japanese outpatients (age 61 ± 9 years, 60 males) on thrice weekly maintenance. End-systolic elastance (Ees), arterial elastance (Ea), and pressure-volume area (PVA) were estimated using a noninvasive single-beat technique. Ventricular-arterial coupling was assessed by Ea/Ees ratio. Measurements were repeated after 2-minute handgrip stress to evaluate cardiac reserve., Results: Resting left ventricular end-diastolic volume index and stroke volume index were significantly larger after a 1-day IDT compared with just after HD and even more after a 2-day IDT. Although Ees, Ea, and Ea/Ees ratio at rest remained similar between short and long intervals, stroke work (SW) and PVA were higher after the long interval. During handgrip stress, a significant increase in Ea without corresponding rise in Ees was observed only after long IDT, resulting in decreased stroke volume index, SW, and SW/PVA efficiency., Conclusions: In a selective Japanese outpatient population on maintenance HD, there were no differences in resting cardiovascular function measured by echocardiography at 3 different IDTs. However, exercise-induced afterload mismatch assessed by the changes in Ea, SV, SW, and SW/PVA efficiency was most pronounced in individuals after the long IDT compared with other IDTs. Our findings report potential pathophysiologic echocardiographic parameters that attempt to explain why cardiovascular events are highest on the day after the long IDT compared to other IDTs in dialysis patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We investigated the risk factors for recurrence of IgA nephropathy after kidney transplantation. Of the 184 recipients of allografts for end-stage renal disease caused by primary IgA nephropathy at our institution and affiliated hospitals between 1990 and 2005, 70 developed recurrent IgA nephropathy (group 1), while the remaining 114 did not develop recurrent IgA nephropathy (group 2). The diagnosis of recurrent IgA nephropathy was based on case and/or protocol renal biopsies. We examined the risk factors for recurrence of IgA nephropathy by comparing the two groups. In addition, we also investigated the risk factors for graft loss in the patients with recurrent IgA nephropathy. The recipient's age at transplantation was significantly younger in group 1 than in group 2 (33.4 ± 10.4 vs. 36.7 ± 10.7, P = 0.037). No significant influence of the immunosuppressive regimens used was observed on the likelihood of recurrence of IgA nephropathy. In the analysis of the risk factors for graft loss, the mean age of the donor was significantly higher in the patient group with graft loss (59.1 ± 9.5 vs. 53.9 ± 9.0, P = 0.033), and the serum creatinine level at one year after surgery was also significantly higher in the patient group with graft loss (1.62 ± 0.52 vs. 1.34 ± 0.34, P = 0.022). Recipients with recurrent IgA nephropathy after transplantation, especially younger patients, need to be followed up carefully., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)

In the past 20 years, over 2,000 cases of ABO-incompatible living kidney transplantation (ABO-ILKT) have been performed in Japan, expanding the donor pool and overcoming the serious shortage of organ donors. Overall long-term outcomes (>20 years) have been excellent and almost identical to the outcomes of ABO-compatible living kidney transplantation (ABO-CLKT). In the last decade, ABO-ILKT has become accepted as a therapeutic alternative for end-stage renal failure. Recently, approximately 30% of all living donor kidney transplantations in Japan have been ABO-ILKT. In the 1990s, desensitization included preoperative plasmapheresis, splenectomy, and heavy immunosuppression that caused surgical and medical stress on patients and a higher cost than that needed for ABO-CLKT for the preoperative conditioning. However, since 2000, rituximab has replaced splenectomy making ABO-ILKT much easier. It is also less stressful for patients. In the last decade, outcomes have improved significantly and 5- and 10-year graft survival have reached 95% and 90%, respectively-identical to, or even better than outcomes of ABO-CLKT. Our current preconditioning includes plasmapheresis 0-2 times, rituximab injection, and regular immunosuppression. Neither intravenous immunoglobulin nor prophylactic plasmapheresis is used after transplantation. ABO-ILKT is a standard option for kidney transplantation requiring minimal preconditioning and regular immunosuppression after transplantation. It now provides an excellent long-term (>20 years) outcome.

Background: Bladder dysfunction after kidney transplantation (KTx) impairs the patients' quality of life. We examined the bladder function status perioperatively in patients undergoing KTx and performed a randomized prospective study to determine the efficacy of an antimuscarinic agent, solifenacin, in ameliorating the bladder dysfunction after KTx., Methods: The subjects in this study were 33 patients who underwent KTx at our institution. The patients were divided into two groups: group 1 (n=18), composed of patients who were not treated with any antimuscarinic agent, and group 2 (n=15), composed of patients treated with an antimuscarinic agent. We investigated the actual bladder function status of these patients before and after KTx by the following two methods: (1) video water cystometry and (2) questionnaire study using the Overactive Bladder Symptom Score and King's Health Questionnaire., Results: The cystometry study revealed a significantly greater increase of the maximum cystometric capacity in group 2 than in group 1 (173.0±60.7 mL in group 1 and 260.1±51.0 mL in group 2 [P=0.005]) after KTx. In the questionnaire surveys, the decreases in the scores for all domains were observed 6 weeks after KTx. The scores in group 2 tended to be lower than those in group 1., Conclusion: In all of our patients, the bladder dysfunction status improved dramatically after KTx. In addition, our results suggest that administration of the antimuscarinic agent, solifenacin, may contribute to improvement of the quality of life of patients undergoing KTx.

Vascular calcification is associated with cardiovascular disease in hemodialysis (HD) patients. Some reports have previously shown that simple assessment of aortic calcification using plain radiography is associated with cardiovascular (CV) events; however, these studies simply assessed whether aortic calcification was present or absent only, without considering its extent. Here, we evaluated the validity of grading aortic arch calcification (AoAC) to predict new CV events. We retrospectively reviewed chest X-rays in 212 asymptomatic HD patients who underwent measurement of pulse wave velocity (PWV) in 2006 without a past history of CV events. The extent of AoAC was divided into four grades (0-3). Among these subjects, the follow-up of CV events in 197 patients was completed. At baseline, AoAC grade was positively associated with age, dialysis vintage, PWV and parathyroid hormone levels, and negatively correlated with body weight and body mass index. Arterial stiffness, as determined by PWV, was also correlated with increasing AoAC grade. Eighty-nine CV events in total occurred during a mean follow-up period of 69 ± 45 months. With multivariate adjustment, Kaplan-Meier analysis showed that the incidence was significantly higher in patients with higher AoAC grade (grades 2 and 3) than in those with grade 0 or 1 (p = 0.013, log-rank test). Multivariate Cox proportional hazards analyses showed the predictive values of AoAC grade were significant (hazard ratio 1.512; p = 0.0351). AoAC detectable on chest X-ray is a strong independent predictor of CV events in accordance with PWV. Risk stratification by assessment of AoAC may provide important information for management of atherosclerotic disease in HD patients.

Aim: Vascular calcification is a cause of cardiovascular death in hemodialysis (HD) patients. The aim of the present study was to evaluate the relationship between the progression of aortic arch calcification (AoAC) and serum fibroblast growth factor (FGF)-23., Methods: The enrolled study subjects were 127 (83 men and 44 women) HD patients. Calcification of the aortic arch was semiquantitatively estimated with a score (AoACS) on plain chest radiology. Change in AoACS (ΔAoACS) was obtained by subtracting the baseline AoACS value from the follow-up AoACS value. The second assessment was performed from 5 years after the first determination., Results: The percentage of male gender in non-progressors (58.5%) was lesser than in regressors (60.0%) and progressors (74.6%). In addition, the dialysis duration in regressors (14.1±5.1 years) was shorter than in non-progressors (19.5±7.0 years) and progressors (16.8±7.5 years). Interestingly, the serum FGF-23 level in regressors (39225.5±9247.9 pg/mL) was significantly higher than in non-progressors (12896.5±26323.5 pg/mL) and progressors (14062.4±18456.8 pg/mL). Multi-ple regression analyses showed male gender (β value=0.969, F=5.092, p=0.0192), serum levels of albumin (β value=-1.395, F=4.541, p=0.0296) and log FGF-23 (β value=-0.001, F=7.273, p=0.0115) to be significant independent determinants of ΔAoACS., Conclusion: Changes in AoAC evaluated by using a simple chest radiograph are associated with serum FGF-23 levels. Excess accumulation of FGF-23 in serum may enable to inhibit the calcification process in vessel walls in chronic HD patients.

Objectives: To evaluate the bladder function of end-stage renal disease (ESRD) patients by using video H(2)O cystometry (CM) before renal transplantation (RTx)., Methods: A total of 92 patients (57 men and 35 women; mean age 45.4 years; mean period of renal replacement therapy (RRT) 60.2 months) were divided in two groups based on the presence of detrusor overactivity (DO). In each group the following parameters were recorded during CM: first sensation (FS), maximum cystometric capacity (MC) and compliance. The effect of the duration of RRT on the H(2)O cystometric results was also assessed., Results: There were 25 patients (27.2%) who had DO before their operation, this ratio being higher than the general Japanese population. Subjects with DO were observed independently for the duration of RRT and there was no difference in the prevalence of DO based on this variable. In contrast, 50 patients kept their bladder compliance in the normal range. The numerical value of FS, MC and compliance decreased proportionally for the duration of RRT., Conclusions: Patients undergoing RTx frequently present with bladder dysfunction in terms of low capacity, low compliance and also DO. This bladder dysfunction has a negative impact on patients' quality of life. Thus, bladder function and its related symptoms require specific attention during the management of transplant patients.

Background: Pulse wave velocity (PWV) and ankle-brachial blood pressure index (ABPI) are markers for atherosclerosis, and each predicts mortality in patients undergoing hemodialysis. However, there have been no studies in the past that compared head-to-head the clinical validity of these 2 parameters. Compared with conventional aortic PWV, brachial-ankle PWV (baPWV) is considered simple and thereby easily applicable to clinical use., Methods: To clarify the relationship between baPWV and ABPI and assess their prognostic values, we analyzed 785 hemodialysis patients with a mean age of 60.2 +/- 12.5 (SD) years for whom ABPI and baPWV at baseline had been measured simultaneously and who were followed up for 33.8 +/- 10.8 months., Results: Of 785 patients, 131 deaths were recorded. In Kaplan-Meier analysis, all-cause mortality was progressively and significantly greater from the lowest quartile of baPWV onward (log-rank test, 41.8; P < 0.001). However, in Cox proportional hazards analysis, the impact of baPWV was insignificant when ABPI was included as a covariate. ABPI maintained strong predictive power in this model. When patients who had advanced peripheral arterial occlusive disease (ABPI < 0.9) were excluded from analysis, patients with the highest quartile of baPWV had significantly increased hazard ratios of all-cause (hazard ratio, 4.08; 95% confidence interval, 1.46 to 11.43; P < 0.007) and cardiovascular (hazard ratio, 7.03; 95% confidence interval, 1.49 to 33.08; P < 0.014) mortality. The predictive power of baPWV in this population was independent from other covariates associated with atherosclerotic disorders., Conclusion: In a head-to-head comparison, ABPI, but not baPWV, showed strong power in predicting the mortality of hemodialysis patients. However, baPWV was useful to pick a high-risk population in patients with ABPI greater than 0.9. Thus, screening hemodialysis patients by means of baPWV and ABPI provides complementary information in identifying a high-risk population.

The most important transplantation antigen system for organ transplantation is the ABO blood group system. Crossing the blood barrier is usually not done except in emergency cases such as liver transplantations for fulminant hepatitis. Early experiences of allograft transplantations across the blood barriers were discouraging. In the 1970s, clinical trials were started transplanting kidneys of subgroup A2 into blood group O recipients because the tissues of the A2 subgroup express a lower amount of A antigens compared with subgroup A1. The recipients required no special treatment and received the standard immunosuppressive regimen as used in blood group identical cases. Many early graft loses immediately after transplantations were experienced, but these trials resulted in an excellent graft survival rate. A few centers have adapted the concept of A2 kidneys to non-A recipient transplantations with successful results by reducing anti-A blood type titers prior to transplantations. In the early 1980s, the possibility of bridging the ABO barrier was tested by several groups. A1 and B kidneys from living donors were also successfully transplanted across the blood barrier using quadruple immunosuppressive drugs and splenectomy. Since 1989, the largest number of ABO-incompatible renal transplantations have been performed in Japan because of the limited numbers of cadaveric donors. Approximately 400 cases have been successfully transplanted across the blood barrier at many centers in Japan. Owing to novel immunosuppressive drugs, the ABO-incompatible allografts exhibited a level of function comparable with that of ABO-matched allografts even though anti-A or anti-B antibodies had returned to the circulation of the recipients. In this article, we describe the historical background, the current therapeutic strategies including apheresis therapy for the ABO-incompatible transplantations, and the experiences at our institution.