Kazunari Tanabe

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study

BackgroundTo investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease.MethodsPTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31xa0years old (median 15xa0years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome).ResultsRenal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5–86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10–107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05–30.3xa0ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases.ConclusionsDownregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Title: Radical prostatectomy for localized prostate cancer in renal transplant recipients: 13 cases studied at a single center

OBJECTIVESnWe aimed to evaluate the feasibility and efficacy of surgical prostatectomy in renal transplant recipients (RTRs).nnnMETHODSnBetween January 2008 and February 2017, we identified 13 RTRs who were diagnosed with localized prostate cancer and underwent radical prostatectomy. We reviewed all available clinicopathologic data for these 13 patients.nnnRESULTSnThe median patient age was 61 years and median serum prostate-specific antigen (PSA) was 8.79 ng/mL. The mean period between transplantation and diagnosis of prostate cancer was 136 months. The sources for the kidney transplants included 10 living and 3 deceased donors. Biopsies indicated that the Gleason scores were 7 in 10 patients and 8 to 10 in 3 patients. Meanwhile, the DAmico risk classification indicated an intermediate risk in 9 patients and a high risk in 4 patients. Eight patients were at stage cT1 and 5 were at stage cT2. The surgical procedure was retropubic radical prostatectomy in one recipient, laparoscopic radical prostatectomy in 3 recipients, and robot-assisted radical prostatectomy in 9 RTRs. Intraoperative complications were not noted in any patient, although one patient demonstrated postoperative complications (Clavien gradexa0≥ 3). An indwelling urinary catheter was required in 3 patients for over 3 weeks due to delayed wound healing. Biochemical recurrence evaluated by PSA monitoring occurred in four patients. Postoperative graft function was stable in all but one patient who required resumption of dialysis before prostatectomy; however, all patients are alive at the time of publication with 12 patients showing well-functioning renal allografts.nnnCONCLUSIONnProstatectomy may be a feasible and effective technique as an initial treatment for RTRs with localized prostate cancer.

Follow-up Survey of Donor Candidates for Living Related Kidney Transplantation With Prostate Cancer

INTRODUCTIONnWith the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer.nnnMETHODSnBetween January 2006 and December 2016, 9 donor candidates for living related kidney transplantation were incidentally diagnosed with prostate cancer at our institution. All male kidney transplant donor candidates routinely received prostate-specific antigen (PSA) testing. The patients with PSA levels > 4.0 ng/mL underwent prostate biopsies. For future kidney transplantation, treatment for localized prostate cancer was prostatectomy.nnnRESULTSnSeven low- or intermediate-risk patients according to the DAmico risk classification underwent endoscopic prostatectomy, while 2 high-risk patients underwent high dose-rate brachytherapy to prioritize prostate cancer treatment. Of the 7 who underwent surgery, 3 patients ultimately became living related kidney transplantation donors for their wives. There was no recurrence of PSA elevation after treatment.nnnCONCLUSIONnThis study showed that donor candidates with prostate cancer could safely donate a kidney after a thorough evaluation to exclude those with high-risk prostate cancer. Transmission of prostate cancer through kidney transplantation seems unlikely and robot-assisted laparoscopic prostatectomy may be feasible for donor candidates with localized prostate cancer.

Comparative study on variation of QOL of preemptive kidney transplantation patients (PKT) and non-preemptive kidney transplantation patients (NPKT) before and after transplantation Running Headline-A questionnaire survey on patients’ QOL in PKT and NPKT

BACKGROUNDnThere have been few studies that have reported the influence of kidney transplantation on the quality of life (QOL) of patients of preemptive kidney transplantation (PKT) and nonpreemptive kidney transplantation (NPKT).nnnMATERIAL AND METHODSnFifty patients of PKT and 49 patients of NPKT were employed as study subjects. A questionnaire survey using Short Form 36 and Kidney Disease QOL on patients physical and psychological QOL was performed for these patients prior to transplantation and 1 month, 3 months, and 1 year after transplantation.nnnRESULTSnThe analysis of results has revealed that transplantation clearly has improved the physical and psychological QOL in patients with end-stage renal disease. For the items regarding physical burdens incurred by the transplantation, patient QOL deteriorated on a single occasion 1 month after the transplantation while it was improved 1 year after the transplantation. For the items regarding psychological burdens, the mental condition of the patients was improved overall without deterioration over time. Concerning the Effect of Kidney Disease and Burden of Kidney Disease, QOL was significantly better in PKT than NPKT at baseline before transplantation, although the significant difference gradually decreased 1 month and 3 months after the transplantation and disappeared after 1 year.nnnCONCLUSIONnTransplantation certainly improved the QOL of patients with end-stage renal disease. Before transplantation, PKT was clearly better than NPKT in the QOL items associated with Burden of Kidney Disease. This indicated that patients of PKT have improved QOL compared to patients of NPKT, and that the overall awareness of kidney disease is decreased. A postoperative gap in mental and bodies was observed especially in PKT, however, could be overcome by nursing interventions.

Effect of Perioperative Blood Transfusions in Renal Transplant Patients

BACKGROUNDnIn patients eligible for organ transplantation, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines specifically recommend avoiding red blood cell transfusions (RBCT) when possible to minimize the risk of allosensitization.nnnOBJECTIVEnTo assess the effect of perioperative RBCT on outcomes in living-related kidney transplantation (LRKT) recipients.nnnMETHODSnWe retrospectively assessed 97 patients who underwent LRKT and whose data were evaluable at our institution between March 2009 and May 2016. We measured serum creatinine levels and calculated the estimated glomerular filtration rate (eGFR) at 3 months, 6 months, and 1 year after kidney transplantation (KTx). We evaluated the rejection rate within a year after KTx. We compared the renal function and rejection rate between those who received blood transfusions (nxa0= 21) and those who did not (nxa0= 76) during the perioperative period.nnnRESULTSnAmong patient characteristics, the rate of ABO-incompatible KTx and the mean hemoglobin levels before KTx differed significantly between the groups. The serum creatinine levels and eGFR within 1 year after KTx did not differ significantly between the two groups. The rejection rate in those who received blood transfusions and those who did not was 28.6% (6/21 patients) and 25.0% (19/76 patients) (Pxa0= .741), respectively.nnnCONCLUSIONSnWe found that the rejection rate was slightly higher in patients who received perioperative RBCT than in those who did not, but the difference was not significant within a year after KTx. Perioperative RBCT may not affect renal function within a year after KTx.

Effect of Influenza Vaccine in Patients with Kidney Transplant

BACKGROUNDnAmong infectious diseases, influenza is the most common cause of infection in Japan and worldwide. We aimed to evaluate the effect of influenza vaccination in kidney transplantation (KTx) recipients.nnnMETHODSnWe retrospectively evaluated the records of 98 participants who underwent KTx at our institution between March 2009 and May 2016. All patients received tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone for maintenance immunosuppression after KTx. In accordance with the criteria of our institution, everolimus was administered for the maintenance of immunosuppression after KTx. We compared the rate of influenza infection during the 2016-2017 season (8 months, from October 2016-May 2017) between KTx patients treated with 1 or 2 doses of influenza vaccine (treatment group, nu2009=u200971) and KTx patients who did not receive a vaccine (nontreatment group, nu2009=u200927).nnnRESULTSnAmong patient characteristics, only the prevalence of diabetes mellitus differed significantly between the groups (treatment group: 9.9%, 7 of 71 patients; nontreatment group: 29.6%, 8 of 21 patients; Pu2009=u2009.02). Influenza infection occurred at similar rates in the 2 groups (treatment group, 5.63% 4 of 71 patients; nontreatment group: 3.70%, 1 of 27 patients; Pu2009=u2009.70).nnnCONCLUSIONSnAmong KTx patients managed in our institution, treatment with 1 or 2 doses of influenza vaccine did not reduce the rate of influenza infection in the 2016-2017 season, suggesting that influenza vaccination may currently be ineffective in KTx patients.

Treatment of Posttransplantation Anemia

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.

Daclatasvir/Asunaprevir Therapy Provides High Tolerability and Effectiveness for HCV-Positive Kidney Transplant Recipients

Background/Aims: Hepatitis C virus (HCV) infection is not rare in kidney transplant (KT) recipients. Interferon (IFN)-based therapies are generally contraindicated because IFN can induce severe rejection of the allograft. Here, we report five cases those who underwent therapy with direct-acting antiviral drugs (DAAs) after KT and evaluated their clinical outcomes. nPatients/Methods: The five patients [the median age; 55 (49- 71) years, 3 males], were treated with NS5A and NS3 proteasetargeted DAA (daclatasvir, DCV and asunaprevir, ASV) therapy for 24 weeks after KT. The immunosuppressants prescribed were corticosteroids/mammalian target of rapamycin, tacrolimus, and mycophenolate mofetil or azathioprine. nResults: In all cases, the acquired HCV was serological type 1 with the L31 or Y93 wild-type strain and the median HCV RNA level was 6.5 (5.7-6.7) log IU/mL. The median estimated glomerular filtration rate (eGFR) was 39 (30-58) mL/min/1.73 m2. All treated cases achieved a sustained virological response (SVR). Therapeutic drug monitoring of tacrolimus required slight adjustments of the tacrolimus dose. Regarding adverse events, a low-grade fever and mild renal dysfunction were observed in one case at 3 months. Despite withdrawing the treatment, this case still achieved SVR. The other cases showed no severe adverse events in liver or renal function. nConclusions: An IFN-free regimen of DCV/ASV therapy provided high tolerability and effectiveness in HCV-positive KT recipients, even under immunosuppressive conditions

The safety and validity of surgical resection for hemodialysis-dependent patients with renal cell carcinomas involving the inferior vena cava

Perioperative morbidity and mortality increase during renal cell carcinoma resection with inferior vena cava involvement in hemodialysis-dependent end-stage renal disease patients. We evaluated the safety and validity of surgical management for renal cell carcinoma with inferior vena cava thrombi in such patients undergoing radical nephrectomies and tumor thrombectomies. There were three patients with tumor thrombus level II, and one each with tumor thrombus level III and IV. We evaluated median operative time (337xa0min), median estimated blood loss (1300xa0mL), and median postoperative hospitalization (15xa0days). Postoperative complications included surgical site dehiscence and pulmonary thromboembolism. One patient with preoperatively identified lung metastases developed a pulmonary thromboembolism on day 3 and died on day 15. The other four patients had long postoperative survival (19–104xa0months). Successful surgical management of renal cell carcinoma involving the inferior vena cava requires preoperative evaluation of the patient’s condition to improve survival for hemodialysis-dependent end-stage renal disease patients.

Long-Term Results of ABO-Incompatible Living Kidney Transplantation. A Single-Center Experience

BACKGROUNDnDespite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT.nnnMETHODSnSixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases.nnnRESULTSnPatient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa