Hepatitis C virus (HCV)-related liver disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) who is treated with hemodialysis (HD). It was reported the prevalence of anti-HCV seropositivity among patients on maintenance HD was 9.84％ at 2007 in Japan. Although the spread of HCV in HD units is declining, the prevalence of HCV in HD patients remains still high. The two major HCV-related complications are reported as liver-related (cirrhosis and hepatocellular carcinoma) and non-liver-related disorders (cardiovascular disease, and so on). These are suspected causes of higher mortality among HCV-positive patients, antiviral therapy is recommended for all HCV patients with HD. Infection with HCV leads to increased serum alanine aminotransferase (ALT) in patients without HD. However, this test has weak diagnostic value in HD patients because ALT tends to be below reference range in this patient group. Therefore, novel non-invasive techniques for assessing liver fibrosis in HD patients with HCV infection are proposed. Two of these are the aspartate aminotransferase toplatelet ratio index (APRI) and transient elastography (TE) which is performed with a Fibroscan^TM machine. Studies have been demonstrated that with conventional interferon (IFN) monotherapy or pegylated IFN monotherapy are similar efficacy and safety in HCV-infected HD patients. Sustained viral responses (SVRs) with these monotherapies have ranged approximately 30％ to 40％. However, remarkable adverse effects including flulike syndrome, fatigue/weakness, and loss of appetite require withdrawal of anti-viral treatment in many patients. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir (DCV) and asunaprevir (ASV), both of which are metabolized in the liver and excreted into the bile ducts, showed a high rate of HCV eradication in HCV-infected patients with genotype 1B. We evaluated the 12-week SVR (SVR12) rate and adverse events during treatment. The safety and viral responses were compared among patients infected with HCV, between 28 patients receiving HD and propensity score-matched 56 patients without renal dysfunction. The rate of SVR12 was 100％ in patients receiving HD and 94.6％ in patients without renal dysfunction. No adverse constitutional events were observed in both of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. DCV and ASV combination therapy for chronic HD patients with HCV infection was highly effective and well tolerated with a comparable safety profile to patients without renal dysfunction.

During human embryogenesis, a single fertilized cell develops into a whole body within 266 days. The resulting neonate has every organ positioned correctly, indicating that this single fertilized ovum contains a blueprint from which the body forms, including the kidney. Therefore, it can be imagined that by applying exogenous pluri- or multi-potent stem cells in the organogenesis niche at exactly the right time, a whole kidney might be regenerated via nephrogenesis programming. This strategy can be categorized into three, depending on the stage of development at which the strategy is applied；the blastocyst stage, the organogenesis stage and the adult stage. Each of these strategies may be applicable in the clinical setting, but a substantial preparation period appears to be required. Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, this “niche strategy” provides hope to dialysis patients and is expected to become reality in the future.

Vaccination against routine diseases is critical to kidney transplant recipients (KTRs) ； details of vaccines recommended for KTRs have been described in several publications. However, in busy clinical practice, KTRs may receive insufficient vaccinations. How much importance is attached to that situation? Vaccination certainly has enormous significance in disease prevention；however, in KTRs, we should take the significance of vaccination one step further. We must fully understand the relevance of infection, kidney dysfunction, and cardiovascular diseases. In other words, prevention of infection with vaccination undoubtedly results in retention of long-term kidney allograft function, reduction of cardiovascular diseases, and finally, improvement in the long-term outcomes of KTRs. Here we present a case to emphasize the significance of vaccination in KTRs. In this case, insufficient vaccination should be recognized as a serious problem. Conclusively, KTRs must be vaccinated to avoid exacerbation of long-term outcomes.

【Objective】To evaluate the risk factors for mortality after kidney transplantation in recipients aged ≥ 60 years.【Patients and Methods】We performed 62 living donor kidney transplants in recipients aged ≥ 60 years at the National Chiba-East Hospital from April 2004 to December 2015. Recipients were divided into the survival (n＝49) and nonsurvival (n＝13) groups. Patients’ preoperative, intraoperative, and postoperative background factors were compared. Additionally, the groups were classified by the cause of death and survival time from the date of the operation to the date of death.【Results】The mean age at transplantation was 63.90±3.18 and 66.92±4.66 years, and the average period of hemodialysis was 3.35±3.42 and 5.94±4.80 years in the survival and non-survival groups, respectively, which were significantly different (p＝0.0079 and 0.0299, respectively). There were no significant differences in the other factors. Infectious diseases or cardiovascular system diseases were common causes of death, with most patients dying within 1 year.【Conclusions】Mortality risk factors in elderly recipients of living donor kidney transplantation were age at the time of transplantation and the period of hemodialysis. Long-term dialysis syndrome should be considered while performing a preoperative adaptation assessment and preoperative treatment. Moreover, the prevention of complications such as cardiovascular and infectious diseases during intensive follow-up in the first year after transplantation can lead to a significant decrease in mortality in elderly recipients of living donor kidney transplantation, thereby increasing the rate of the long-term graft survival in elderly people.

【Objective】For detection of Donor Specific Antibodies (DSA), solid phase immunoassays (SPI) have been used widely；however, reactions with serum samples are ambiguous among commercial reagents. We evaluated the results produced by two antibody detection assays：LABScreen^Ⓡ Single Antigen (LSSA) and WAKFlow^Ⓡ HLA Class I (HR).【Method】We compared the results between LSSA and HR on 24 serum samples where LSSA detected HLA antibodies. The antibodies of interest were 43 HLA antibodies that are shared between LSSA and HR. The total number of assayed antibodies in this study was 1,032.【Result】The concordance rate for LSSA and HR was 94.7％. There were 31 cases (antibodies) where LSSA showed a positive reaction whereas HR yielded a negative one. On the other hand, there were 24 cases where LSSA showed a negative reaction, but HR produced a positive result.【Conclusion】There are mismatches between the results of LSSA and HR for a number of antibodies. For detection of DSA, serological methods in addition to SPI may be necessary.

【Purpose】At Nagasaki University we underwent the first case of kidney transplantation in 1965. During the approximately 50 years until 2015, we carried out renal transplant of 226 cases. Herein we report the outcome of the cases in our institute of the fifty-year history.【Materials and Methods】We underwent 74 cadaveric renal transplantations and 152 living kidney transplantations. The mean age of recipients was 37±13 years, and the mean age of donor was 48±13 years. The cause of end-stage renal disease was chronic glomerulonephritis (n=174), the diabetic nephropathy (n=8), and other disease (n=44). The mean duration of dialysis prior to transplantation was 63 months.【Results】The follow-up period of the 226 patients was 9.3±8.9 years. We analyzed the cases of long-term allograft survival. 31 cases obtained graft survival period of more than 20 years (14%) and 5 cases (2.2%) obtained one of more than 30 years. The graft survival of cadaveric donor kidney transplantation at 5 years and 10 years was 65.4%, and 55.8%, and the graft survival of living donor kidney transplantation at 5 years and 10 years was 76.2%, and 70.1%. In the recognized loss of function of the 114 cases, cause of graft loss was chronic allograft dysfunction in 49 cases (42%), and the deaths in 41 cases (36%), and acute rejection in 19 patients (17%)【Conclusions】We summarized the 226 cases of kidney transplantation in Nagasaki University. Our clinical experience was considered to be history itself in Japan of kidney transplantation.

【Background】The impact of tertiary hyperparathyroidism (tHPT) on long term graft survival has been suggested. The purpose of our study was to evaluate the relationship between intact PTH (iPTH) and long term patient outcomes after kidney transplantation.【Methods】We retrospectively analyzed long-term patient outcomes for consecutive patients at Chiba East Hospital between January 2005 and December 2011. Fifty two patients had the follow-up data of iPTH. High PTH group were defined as iPTH＞188 pg/dL (median in this study) and low PTH group were defined as iPTH≦188 pg/dL. We used iPTH as a predictor and composite endpoint (death, restarting dialysis and increase of creatinine for 1.5 times) as a primary outcome. Cox proportional hazards models were used to compare the outcomes between two groups, adjusting for age and time on dialysis.【Results】Twenty three were male and twenty nine were female. The mean age was 48±10 and mean time on dialysis was 7.9±6.5 years. Baseline laboratory data were as follows；Cr 1.4±0.4 mg/dL, Ca 10.5±1.0 mg/dL, Pi 2.6±0.7 mg/dL and iPTH after kidney transplantation was 233±176 pg/mL. The mean follow-up term was 101 months. In univariate Cox proportional hazards analysis, high PTH group was significantly associated with worse long-term outcome (hazard ratio [HR] 3.7；95％ confidence interval [95％ CI], 1.1 to 12.3；p＝0.03). Multivariate analysis showed high PTH group was a marginally significant predictor of worse outcome (HR, 4.0；95％ CI, 0.97 to 16.8；p＝0.054).【Conclusion】The present study demonstrated that iPTH after kidney transplantation might be an important factor of patient outcome.

【Aim】We examined the efficacy of selective plasma exchange (SePE) in ABO-incompatible kidney transplantation.【Background】In ABO-incompatible kidney transplantation, double-filtration plasmapheresis (DFPP) or simple plasma exchange (PE) are usually performed, but both methods have problems, including an increased risk of perioperative bleeding due to decreased levels of coagulation factors in DFPP, and allergic reactions to fresh frozen plasma (FFP) in PE. In this study, we examined the efficacy of SePE using Evacure PLUS EC-4A10 (Kawasumi Laboratories, Inc., Tokyo, Japan), a selective plasma separator with a smaller pore size than conventional membrane plasma separators.【Methods】SePE was performed in 7 ABO-incompatible kidney transplant recipients to remove antibodies. The EC-4A10 was used with a treatment volume of 1.5 to 2 PV and a 5％ albumin solution as replacement fluid. Anti-blood type antibody, IgG, IgM and fibrinogen titers were measured, and titer decreases and removal of antibodies after SePE were determined.【Results】SePE was performed a total of 13 times. After exclusion of one patient with a high antibody titer, the IgG antibody titer decreased by 2 to 4 fold, the IgM titer decreased by 0 to 1 fold, and the rates of removal of IgG, IgM and fibrinogen were 67.9±6.3％, 10.6±7.1％ and 30.5±6.3％, respectively. There were no particular side effects.【Conclusions】Serum antibody titers can be reduced by SePE using the EC-4A10 in recipients with lower antibody titers, with little loss of coagulation factors and few side effects. These findings suggest that SePE may be effective for apheresis in ABO-incompatible kidney transplantation.

【Objective】From January 2007, we employed laparoscopic live donor nephrectomy. We summarized the surgical outcome of this procedure.【Material and Methods】We retrospectively compared the surgical outcome of laparoscopic live donor nephrectomy (63 cases：L group) and those of mini-incision endoscopic live donor nephrectomy (29 cases：M group).【Results】While L group needed significantly longer operation time compared to M group (329.0±69.0, 279±45.7min, p＜0.05), estimated blood loss and warm ischemia time seemed equivalent between L group and M group. L group was sub-grouped to initial 30 cases (initial phase) and following 33 cases (late phase) to compare the surgical outcome between these two subgroups. Mean operation time and estimated blood loss were significantly reduced in the late phase subgroup (374±67.7min, 295±59.0min, p＜0.01) (754±97.4mL, 282±92.8mL, p＜0.01). In the late phase, mean operation time of the L group was comparable of those with M group and estimated blood loss was significantly decreased in L group compared to those of M group.【Conclusions】In the initial case of L group, mean operation time was longer, and estimated blood loss was higher compared to late phase, but improved with increasing experience of L group.

【Objectives】Renal allografts from grandparents as well as parents are commonly used in pediatric living donor kidney transplantation (LKTx). The aim of this study was to investigate the impact of donor age on renal allograft function and histology.【Methods】We retrospectively analyzed clinical data of 63 recipients who were divided into three groups based on the donor age (30s, 40s, and over 50s). Outcome measures included eGFR after LKTx and ci/ct/ah scores determined by Banff classification in 0-hour and one-year protocol biopsy specimens.【Results】Maximum eGFR was lower and ci/ct/ah scores in 0-hour biopsy specimens were higher in the over 50s group than in the other groups. eGFR steadily decreased in all groups during one year of LKTx, lowest in the over 50s group. In one-year protocol biopsy, calcineurin inhibitor (CNI) toxicity was more frequently observed in the 40s and the over 50s groups than in the 30s group.【Conclusions】More careful management against CNI toxicity would be warranted in pediatric LKTx from donors aged over 50s.

【Introduction and aims】Chronic kidney disease-bone mineral disorders (CKD-MBD) is an important complication in CKD patients, and could affect long term prognosis of renal function after renal transplantation (TPL). We examined the influence of the factors associated with CKD-MBD on renal function before and 1-year after renal TPL.【Methods】We investigated 105 CKD patients who received renal TPL from living donors after 1995. The end point of this study was the 1.5-times increase of minimum serum creatinine (Cr) during the observational period after renal TPL, and examined the relation between CKD-MBD and renal function before and 1-year after renal TPL.【Results】During follow-up period, the 1.5-times increase in Cr occurred in 39 recipients (33.9%). It was associated with younger age, higher iPTH before TPL (p＝0.021) and lower hemoglobin 1-year after renal TPL (p＝0.003) compared with the recipients without the increase in Cr. The patients were separated into 2 groups with the median of iPTH before TPL (155 pg/mL), one group was the higher iPTH group；the other was the lower iPTH group. The Kaplan-Meier analysis showed the higher iPTH were significantly associated with the increase in Cr (p＝0.048).【Conclusions】The status of CKD-MBD before renal TPL might be associated with the progression of renal damage after renal TPL.

CMV infection is one of the most important morbidity after kidney transplantation. Recent advancement of diagnostic tool such as CMV Ag method and PCR, and/or GCV/VGCV production and clinical application served early diagnosis and effective treatment, however, several refractory organ/tissue invasive disease caused by GCV resistant CMV mutants have been reported elsewhere in Japan and worldwide. In this article, I would like to review the up to dated diagnosis, treatment and prophylaxis guidelines and introduce the results from our multicenter research on the early diagnosis of the GCV resistant CMV mutants supported by the grant from Japan Society of Clinical Renal Transplantation.

Demographic data and outcome of pediatric kidney transplantation in Japan were reviewed based on the Japanese Renal Transplant Registry data from the Japanese Society for Clinical Renal Transplantation and the Japanese Society for Transplantation. The children were defined as patients who had not yet attained their 20th birthday at the time of their transplant. A total of 2,876 kidney transplantations have been performed in children in Japan between 1964 and 2014. Transplants were categorized into 4 time periods (1964 ～ 1985, 1986 ～ 1995, 1996 ～ 2001, and 2002 ～2014) to reflect changes in immunosuppression practices over time (in general, introduction of cyclosporine, tacrolimus, mycophenolate mofetil, and basiliximab). Patient demographics have changed over time with an increase in the percentage of younger recipients, pre-emptive kidney transplantation and ABO-incompatible kidney transplantation. Patient survival and graft survival have improved tremendously over time. The 5- and 10-year Kaplan-Meier estimates of patient/graft survival in living donor recipients were 98.9/96.4％ and 98.1/92.3％ in the 2002 ～ 2014 cohorts. Also, the 5- and 10-year Kaplan-Meier estimates of patient/graft survival in deceased donor recipients were 98.1/83.5％ and 96.6/68.0％ in the 2002 ～ 2014 cohorts. More efforts to define the clinical features and outcome of pediatric kidney transplant patients are essential for better treatments for children with end-stage renal disease.