Individualized concept for the treatment of autosomal recessive polycystic kidney disease with end-stage renal disease.

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 m2 . 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.

Monoclonal immunoglobulin G deposits on tubular basement membrane in renal allograft: is this significant for chronic allograft injury?

BACKGROUND: Tubular basement membrane immune deposits (TBMID) has rarely been observed in renal allografts. It is usually found in BK virus nephropathy and immune complex glomerulonephritis; however, its significance is not well understood. We conducted a retrospective clinicopathological study on monoclonal immunoglobulin G (IgG) TBMID. METHODS: We studied 7177 renal allograft biopsy specimens obtained from Tokyo Women's Medical University from 2007 to 2015 and performed light microscopic, electron microscopic and immunofluorescence studies. RESULTS: Tubular basement membrane (TBM) deposits of IgG were found in 73 biopsies from 61 patients and the IgG subclass was obtained in 31 biopsies. There were no cases of monoclonal IgA or IgM TBMID. In total, 13 biopsies from 10 patients showed monoclonal IgG TBMID. Of these, seven showed monoclonal IgG1κ TBMID and one each showed monoclonal IgG2κ, IgG2λ and IgG3κ TBMID. Conversely, eight patients showed polyclonal IgG TBMID. In electron microscopy, large granular electron-dense deposits (EDDs) in the TBM were detected in all patients with monoclonal IgG1κ TBMID. EDDs were absent in TBM in patients with monoclonal IgG2κ, IgG2λ or IgG3κ TBMID. Progression of interstitial fibrosis and tubular atrophy (IFTA) was significantly higher in patients with monoclonal IgG1κ TBMID than in those with polyclonal IgG TBMID (P < 0.05). There were no significant differences in the other clinical parameters between monoclonal IgG1κ and polyclonal IgG TBMID. CONCLUSIONS: This is the first study of patients with monoclonal IgG TBMID in renal allografts. We found that monoclonal IgG1κ TBMID was associated with EDD formation in TBM and IFTA progression.

Longterm renal allograft survival after sequential liver-kidney transplantation from a single living donor.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

BACKGROUND: Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. METHODS: Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. RESULTS: Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. CONCLUSION: Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Recurrence of diabetic kidney disease in a type 1 diabetic patient after kidney transplantation.

Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.

Anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, suppresses human to bovine cellular responses.

UNLABELLED: The effect of an anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, against the human to bovine cellular response was investigated. METHODS: Human peripheral mononuclear cells (PBMCs) were cocultured with inactivated self-PBMCs (Self), bovine PBMCs with control antibody (Xeno), or bovine PBMCs with IMMU-114 (IMMU-114). Cellular responses were investigated by thymidine incorporation assay, CFSE (carboxyfluorescein diacetate succinimidyl ester)-mixed lymphocyte reaction, and cytokine production in culture medium. RESULTS: Thymidine incorporation rates at a 1:1 responder to stimulator ratio for Xeno + control antibody, Xeno + IMMU-114, Self + control antibody, and Self + IMMU-114 were 14201.3 ± 1968.4, 513.0 ± 49.5, 952.7 ± 128.7, and 423.3 ± 138.8 cpm, respectively (P = 0.032). Those at a 1:2 ratio were 6518.0 ± 690.1, 896.6 ± 92.9, 1051.0 ± 123.6, and 736.0 ± 35.6 cpm, respectively (P = 0.036). CFSE-mixed lymphocyte reaction demonstrated that the frequencies of CFSE-low, CD4(+), and CD25(+) activating T cells in Self, Xeno, and IMMU-114 were 0.27 ± 0.04%, 3.65 ± 0.53%, and 1.23 ± 0.15%, respectively (P = 0.027). Cytokine production in culture medium indicated that IMMU-114 decreased Th1-type cytokines, including interleukin-2, interferon-γ, and tumor necrosis factor-α. CONCLUSION: IMMU-114 effectively suppresses human to bovine cellular responses. The mechanism involves direct inhibition of the interaction between class II human leukocyte antigen-DR-positive cells and CD4(+) T cells, and indirect suppression of Th1 cytokine production.

Nine-yr experience of 700 hand-assisted laparoscopic donor nephrectomies in Japan.

OBJECTIVE: We reviewed the introduction of a new, minimally invasive, live kidney donation program in our department. METHODS: The operating times of 700 consecutive hand-assisted laparoscopic donor nephrectomies (HALDN) conducted from February 2001 to April 2010 were examined. The risk factors for prolonging operating times were analyzed and major surgical barriers in HALDN investigated. RESULTS: All procedures were successfully performed without the requirement for conversion to open surgery or blood transfusion. The overall prevalence of perioperative complications was 3.0%, with no mortality, in this non-obese donor population with mean body mass index (BMI) as low as 23.2 ± 3.2 kg/m(2) . After the initial learning curve, a second learning plateau was detected until around case 300. Multivariate analyses showed that the significant risk factors were male sex, graft weight, number of renal arteries, right nephrectomy, and previous epigastric surgery (p < 0.05). HALDN provided direct handling of the surgical field, secure vascular control, safe manipulation of adhesive tissues, and served to maintain surgical safety. Mean values of the BMI of donors had a significant positive correlation with the prevalence of complications between large studies (p = 0.042). CONCLUSIONS: Laparoscopic donor nephrectomy was safely introduced and established in a single institution with the help of the hand-assistance method.

Acute kidney injury as defined by the RIFLE criteria is a risk factor for kidney transplant graft failure.

Acute kidney injury (AKI) is not recognized as a major complication at the maintenance phase after kidney transplantation (KTx). Moreover, it is not clear whether the onset of AKI leads to graft failure. We examined the incidence of AKI that developed three months or later after KTx at our institute. We examined whether the incidence of AKI defined by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage kidney disease criteria associates with graft failure by matched-pair Cox regression analysis. A total of 289 patients were available for the final analysis. The overall incidence of AKI was 20.4%, and the common etiology of AKI was bacterial infectious diseases. The group that developed AKI had significantly lower graft survival than non-AKI group independently of acute rejection. AKI Risk represented a high risk for graft failure and AKI Injury/Failure represented a higher risk for graft failure. The analysis by the AKIN classification yielded the similar results. These results indicate that AKI is a relatively common complication of KTx and represents the major risk for graft failure. We should make every effort in the prevention and early detection to avoid the occurrence of AKI and the subsequent graft failure after KTx.

Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

BACKGROUND: While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. PATIENTS AND METHODS: Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. RESULTS: Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. CONCLUSION: These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

Evaluation of factors influencing the ratio of the trough blood concentration to dose level of everolimus in Japanese kidney transplant recipients.

BACKGROUND: No factors influencing the blood everolimus (EVL) concentrations has been identified until date. Our aim was to identify factors that can affect the ratio of the trough blood concentration to dose level (C0/D ratio) of EVL in kidney transplant recipients. METHODS: We retrospectively analyzed 448 patients who had undergone kidney transplantation and were subsequently being managed as our hospital between 2011 and 2015. Multivariate analysis were performed in an attempt to identify factors affecting the EVL C0/D ratio. RESULTS: The numbers of patients receiving calcineurin inhibitor (CNI)-free regimen and regimen containing cyclosporine (CsA) or tacrolimus (TAC) were 47, 137 and 264 respectively. The EVL C0/D ratio did not differ significantly between the TAC(+) group and the CNI-free group, while it was significantly higher in the CsA(+) group than the TAC(+) group (p < 0.0001) and CNI-free group (p = 0.0003). In the multivariate analysis, age, gender, diabetes mellitus as a cause of the end-stage renal disease (ESRD), CsA, serum creatinine, and hemoglobin were selected as factors affecting the EVL C0/D ratio (R2 = 0.269, p < 0.0001). Using the stepwise method, although mycophenolate mofetil treatment was selected, did not differ significantly according to multiple linear regression analysis. Furthermore, concomitant use of CsA was identified as the most impactful factor, based on the standardized partial regression coefficients (ß = 0.341). CONCLUSIONS: We obtained an indication of patient characteristics that influences the EVL C0/D ratio. But the accuracy of the regression equation obtained from multiple regression analysis was poor (R2 = 0.269), and it was not accurate enough to predict the EVL C0/D ratio and use it for therapeutic drug monitoring.

Renoprotective effect of erythropoietin against ischaemia-reperfusion injury in a non-human primate model.

BACKGROUND: The renoprotective effect of erythropoietin (Epo) against ischaemia-reperfusion injury (IR/I) was evaluated in a non-human primate model. METHODS: Crab-eating macaques were divided into two groups: Control (n = 10), treated with saline, and EPO (n = 10), treated with Epo. Epo was injected intravenously at a dose of 12,000 units, 5 min before clamping the renal pedicle and 5 min before declamping. Renal IR/I was created by clamping the left renal artery for 90 min following right nephrectomy. Haemoglobin (Hb), haematocrit (Ht), creatinine (Cr), blood urea nitrogen (BUN), cystatin C and interleukin-6 (IL-6) were measured before (Pre) and after (Day 0) the operation, and on post-operative days: Day 1, Day 3, Day 5 and Day 7. Apoptotic cells were counted on Day 1. RESULTS: There were no differences in Hb and Ht between the two groups. Cr, BUN, cystatin C and IL-6 levels in the EPO group were lower than those in the Control group at most of the observation points. The number of apoptotic cells in the Control was significantly higher than that of and EPO group. CONCLUSIONS: Epo significantly ameliorates renal IR/I in this non-human primate model. Our findings justify the clinical application of Epo, not only for acute renal failure, but also in transplantation.

The relative role of fibroblast growth factor 23 and parathyroid hormone in predicting future hypophosphatemia and hypercalcemia after living donor kidney transplantation: a 1-year prospective observational study.

BACKGROUND: Kidney transplantation (KTx) restores many of the disorders accompanying end-stage renal failure. However, hypercalcemia and hypophosphatemia are both common complications after renal transplantation. Prospective observation of these complications has not been well described and pre-transplant predictors also remain unknown. This prospective observational cohort study was carried out to clarify pre-transplant risk factors of persistent hypophosphatemia and/or hypercalcemia at 12 months after transplantation. METHODS: Consecutive living donor KTx recipients (n = 39) at Tokyo Women's Medical University were prospectively recruited. Parameters of bone and mineral metabolism including intact parathyroid hormone (iPTH) and full-length fibroblast growth factor (FGF) 23 were followed. RESULTS: FGF23 decreased to comparable levels for renal function while hyperparathyroidism persisted at 12 months after transplantation. Multivariate linear regression analysis revealed that pre-transplant iPTH correlated with hypercalcemia at 12 months and pre-transplant FGF23 was the best pre-transplant predictor of persistent hypophosphatemia at 12 months. CONCLUSIONS: It is intriguing that although FGF23 is not a causal factor for hypophosphatemia at 12 months post-transplantation, it is a significant predictor of this common complication.

Very low but stable glomerular filtration rate after living kidney donation: is the concept of "chronic kidney disease" applicable to kidney donors?

BACKGROUND: Renal prognosis and outcome of Japanese kidney donors, who have lower preoperative glomerular filtration rate (GFR) and are generally older than their counterparts abroad, have scarcely been investigated. Here, the longitudinal changes in renal function of Japanese kidney donors were studied to clarify the prevalence and consequences of low GFR. METHODS: We reviewed charts of the living kidney donors and followed renal function by estimated GFR (eGFR, ml/min/1.73 m(2)) from the time of transplantation (n = 237), until 1 (n = 162) to 3 years after donation (n = 77). RESULTS: Median eGFR at the time of transplant was 78.7. GFR declined by approximately 40% at 1 year after donation, and as a result, most (85%) Japanese kidney donors developed chronic kidney disease (CKD) stage 3, with a median eGFR of only 48.0. The result, that the mean change in eGFR at 1-3 years after donation showed a steady increment of 0.97 ml/min/1.73 m(2) per year, was distinct from the generally accepted notion that GFR declines with age. This upward change was seen irrespective of the absolute values of eGFR at or 1 year after donation, even including a subgroup with the lowest postoperative eGFR of <40. CONCLUSION: Most Japanese donors developed CKD stage 3 after donation but without subsequent progression, at least for several years. Although CKD is in general regarded to confer a significant risk for progressive kidney disease, this notion might not apply to living kidney donors with low GFR but without the risk factors for progression.

Preoperative assessment system for hand-assisted laparoscopic donor nephrectomy by discriminant analysis.

We developed a preoperative assessment system to predict surgical workload in hand-assisted laparoscopic donor nephrectomy (HALDNx) using the normal-based linear discriminant rule (NLDR). A total of 128 cases of left HALDNx performed by a single operator were used as training data. Surgical workload was measured by operative time. The optimized model had 9 explanatory variables: age, total protein, total cholesterol, number of renal arteries (numberRA), 4 variables of perinephric fat (PNF), and thickness of subcutaneous fat. This model was validated using cross-validation and the .632 estimator to estimate discrimination rates with future test data. PNF and numberRA were the predominant factors affecting workload followed by the computed tomography value of PNF, body weight, and male sex. The estimated accuracy of the prediction system was 94.6%. The complication rate was 9.38% and did not correlate with surgical workload. We also made our program available online for constructing assessment functions from other cohort data. In conclusion, the surgical workload of HALDNx could be predicted with PNF and numberRA as the dominant risk factors.

Graft Loss Following Onset of Schizophrenia Long After Liver Transplantation.

Information regarding new-onset posttransplant psychotic disorders and their effect on nonadherence and posttransplant outcome is quite limited. We report a case of new-onset posttransplant schizophrenia that led to death. The patient, a woman with Wilson disease but no history of psychiatric problems or a substance use disorder had undergone liver transplantation at age 21. She married subsequently and bore children, being well able to handle her housework, child care, and full-time employment. She continued her medications as prescribed, and good graft function was maintained. At age 41, she experienced an episode of schizophrenia, then graft loss associated with nonadherence to immunosuppressive agents. Death ensued, occurring 6 months after the onset of schizophrenia. This case highlights the possibility that schizophrenia manifesting long after liver transplantation can result in graft loss and death due to medication nonadherence. Thus, awareness of the possibility of this rare clinical scenario is critical.

A Clinical Trial With Adoptive Transfer of Ex Vivo-induced, Donor-specific Immune-regulatory Cells in Kidney Transplantation-A Second Report.

BACKGROUND: Although the outcome of kidney transplantation (KTx) has improved, various adverse effects of immunosuppressants and chronic rejection aggravate the long-term prognosis of patients. Therefore, the induction of immune tolerance may be an effective therapeutic strategy. METHODS: A clinical trial aiming at immune tolerance induction was conducted in kidney transplant recipients from HLA mismatched living donors by infusing autologous donor-specific regulatory T cells (Treg). To obtain Treg, recipient's peripheral blood mononuclear cells were cocultured with irradiated donor cells in the presence of anti-CD80/CD86 monoclonal antibody for 2 weeks. For preconditioning, splenectomy + cyclophosphamide (CP) was employed in the first series (group A; n = 9). In group B, splenectomy was substituted by preadministration of rituximab (group B; n = 3). In the latest cases, rituximab + rabbit antithymocyte globulin was administered instead of cyclophosphamide (group C; n = 4). Twelve days after KTx, the cultured cells were intravenously infused, and immunosuppressants were gradually tapered thereafter. RESULTS: Although mixed lymphocyte reaction was remarkably suppressed in a donor-specific fashion, 6 out of 9 patients from group A, 1 out of 3 from group B, and 1 out of 4 from group C developed acute rejection within 1 year after KTx. Complete cessation of immunosuppression was not achieved, and a small dose of immunosuppressants was continued. CONCLUSIONS: The adoptive transfer of autologous ex vivo-expanded Treg is 1 of the options to possibly induce alloimmune hyporesponsiveness. However, in the present study, further regimen optimization is still required and should be the focus of future investigations.

Glomerular Neovascularization in Nondiabetic Renal Allograft Is Associated with Calcineurin Inhibitor Toxicity.

INTRODUCTION: Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. METHODS: A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women's Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. RESULTS: In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. CONCLUSION: PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.

An experimental model of encapsulating peritoneal sclerosis.

In Japan, only about 3% of all patients with end-stage renal disease are maintained by continuous ambulatory peritoneal dialysis (CAPD). Although the reasons for the low proportion of patients receiving CAPD are multifactorial, encapsulating peritoneal sclerosis (EPS), a fatal complication of CAPD, is a major factor. In 1995 we developed a rat model of EPS, and in 2001 also developed an EPS model in mice. These rodent EPS models are reliable, reproducible, and inexpensive and have been used by other investigators. The renin-angiotensin system negatively regulates the transforming growth factor-beta signaling pathway, which plays a major role in tissue fibrosis. To investigate the anti-EPS effect of renin-angiotensin system inhibition, an angiotensin-converting enzyme inhibitor, quinapril, was administered to an EPS model in mice. Quinapril was found to inhibit EPS, both macro- and microscopically, in a dose-dependent manner. We report our experience of developing the experimental in vivo EPS model, and the inhibitory effect of this angiotensin-converting enzyme inhibitor on EPS.

Primary Nonfunction on Kidney Transplant Recipients From Donation After Circulatory Death Donors.

BACKGROUND: The need for donor pool expansion remains an important task for kidney transplantation. The aim of this study is the evaluation of primary nonfunction (PNF) from donation after circulatory death (DCD) kidneys. METHODS: Between 1996 and 2017, 100 kidney transplants from DCD donors were conducted in our department. We retrospectively analyzed PNF of kidney transplant recipients from DCD donors in terms of donors' and recipients' epidemiologic characteristics. RESULTS: Of 100 grafts, 95 recipients (95.0%) had discontinued hemodialysis at the time of hospital discharge. Only 5 recipients (5.0%) developed PNF. All 5 PNF recipients received a single graft from an expanded criteria donor (ECD). The mean donor age in the PNF group was 65.0 (SD, 6.2) years. Significant differences between the PNF group and discontinued dialysis group were found for donor age (P < .01) and for the use of ECD kidneys (P < .02). Nevertheless, no significant difference was found between groups for several factors: a history of hypertension and cerebrovascular events, terminal creatinine levels, and graft weight. CONCLUSION: The incidence of PNF from DCD kidneys was very low. Although ECD kidneys in older donors might be a significant risk factor for PNF, these findings suggest that DCD kidneys should be used more frequently for donor expansion.