Rejection In Renal Transplant Recipients Research Articles

Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression.

Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93-1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99-1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.

Impact of peri-operative red blood cell transfusions for treatment of anemia on acute rejection in renal transplant recipients

IntroductionAnemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia. Project aimThe current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation. DesignThis was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%). ResultsLiving donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection. ConclusionOur findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.

P500 Effects of donor-specific human leukocyte antigen and non-human leukocyte antigen antibodies on antibody-mediated rejection in renal transplant recipients

P500 Effects of donor-specific human leukocyte antigen and non-human leukocyte antigen antibodies on antibody-mediated rejection in renal transplant recipients

Long-term CMV monitoring and chronic rejection in renal transplant recipients.

Cytomegalovirus (CMV) is well established to be an independent risk factor for graft loss after kidney transplantation (KTx). Monitoring for CMV in the chronic phase is not defined in the current guideline. The effects of CMV infection, including asymptomatic CMV viremia, in the chronic phase are unclear. We performed a single-center retrospective study to investigate incidence of CMV infection in the chronic phase, defined as more than 1 year after KTx. We included 205 patients who received KTx between April 2004 and December 2017. The CMV pp65 antigenemia assays to detect CMV viremia were continuously performed every 1-3 months. The median duration of the follow-up was 80.6 (13.1-172.1) months. Asymptomatic CMV infection and CMV disease were observed in 30.7% and 2.9% in the chronic phase, respectively. We found that 10-20% of patients had CMV infections in each year after KTx which did not change over 10 years. The history of CMV infection in the early phase (within 1 year after KTx) and chronic rejection were significantly associated with CMV viremia in the chronic phase. CMV viremia in the chronic phase was significantly associated with graft loss. This is the first study to examine the incidence of CMV viremia for 10 years post KTx. Preventing latent CMV infection may decrease chronic rejection and graft loss after KTx.

Emerging Antibodies in Cancer Therapy

Since the first monoclonal antibody, Orthoclone OKT3, was approved in 1986 for the treatment of acute allograft rejection in renal transplant recipients, the number of antibody‐based therapies has increased remarkably, with more than 130 monoclonal antibodies being currently available. In particular, due to their robust binding affinity and high specificity, various monoclonal antibodies have achieved success as complementary antitumor drugs. Moreover, therapeutic potency can be improved by engineering Y‐shaped binding sites of the antibodies to simultaneously recognize two distinct antigens; such molecules are called bispecific antibodies and function as a bridge, with one site binding to a tumor‐specific antigen and the other to immune cells to activate host immune responses. In addition, the development of trispecific antibodies has led to further enhancement of therapeutic specificity and effects. Indeed, a variety of structurally engineered antibodies have proven effective in tumor therapy. This article provides insights into the clinical translation of emerging antibody constructs, firstly describing conventional T cell‐redirecting bispecific antibodies and subsequently discussing the application of bispecific and trispecific antibody constructs based on innate immune cell recruitment. Finally, bispecific antibodies against mutant p53 and KRAS that have been actively studied in cancer treatment are introduced.

Prospective study to evaluate the effectiveness of donor-derived cell-free DNA for early diagnosis of biopsy-proven rejection in renal transplant recipients

Prospective study to evaluate the effectiveness of donor-derived cell-free DNA for early diagnosis of biopsy-proven rejection in renal transplant recipients

332.12: Association Between CYP3A5*1 and CYP3A5*3 Polymorphisms, With the Formation of ADES and the Presence of Rejection in Renal Transplant Recipients

332.12: Association Between CYP3A5*1 and CYP3A5*3 Polymorphisms, With the Formation of ADES and the Presence of Rejection in Renal Transplant Recipients

Pre-transplant Ratio of Firmicutes/Bacteroidetes of Gut Microbiota as a Potential Biomarker of Allograft Rejection in Renal Transplant Recipients

The advent of technologies has made allogenic transplantation a potential curative therapy for end-stage renal diseases, but the episodes of rejection still remain as one of the challenges in the post-transplant scenario. In the recent years, several human and animal studies have elucidated that gut microbial dysbiosis is closely linked with allogenic transplantation and post-transplant complications. But most of the studies focused on the use of high through-put sequencing technologies to analyze gut microbiota despite of its high cost, analysis and time constraints. Hence, in this work we aimed to study the impact of the two dominant gut phyla Firmicutes and Bacteroidetes on 38 renal transplant recipients, before and after transplantation and to find its association with allograft rejection. Significant changes (p&lt;0.01) were observed in the relative abundances of the phyla Firmicutes and Bacteroidetes at pre- and post-transplant period. We have also found that the recipients who had an increase in Firmicutes/Bacteroidetes (F/B) ratio before transplant were highly prone to rejection in the first-year post-transplant. The Receiver Operating Characteristic (ROC) curve analysis has shown that the ratio of F/B were able to discriminate between rejection and non-rejection cases with an Area under the ROC Curve (AUC) of 0.91. Additionally, we observed that the ratio of F/B have reduced during the time of rejection postulating that gut microbial dysbiosis has more association with rejection. Thus, the assessment of F/B ratio using qPCR would be of a more practical approach for diagnosis and monitoring of graft function in a cost-effective and timely manner.

Prognosis and Treatment for Active and Chronic Antibody-Mediated Rejection in Renal Transplant Recipients; Single Center Experience

The aim of the study was to evaluate the prognostic factors and treatment alternatives of antibody-mediated rejection (ABMR) in renal transplant patients. Three thousand renal transplant patients were included in the study. The patients were first divided into 2 groups. Group 1: ABMR [-] recipients (n=2871), Group 2: ABMR (+) recipients (n=129). ABMR patients were compared among themselves by dividing them into 3 subgroups (early-active, late-active, chronic-active). The study was performed retrospectively. Different combinations of methylprednisolone, intravenous immunoglobulin (IVIG), rituximab, plasmapheresis (PP), anti-thymocyte globulin (ATG) were used in the treatment and the results were compared. Graft survival and functions were worse and the rates of CAD, delayed graft function, BK virus, and cytomegalovirus higher in patients with ABMR. Also, graft survival was lower in patients with serum creatinine ≥3 (P=0.001), GFR <30 (P <0.001), and spot urine protein to creatinine ratio ≥1 (P = 0.042) at the time of diagnosis. High interstitial fibrosis and tubular atrophy scores in chronic ABMR cases and high intimal arteritis scores in active ABMR cases were poor prognostic factors. The study showed that ABMR has a poor prognosis in terms of clinical parameters, and treatment should be individualized according to pathologic findings and graft functions at the time of diagnosis. Pulse methylprednisolone and IVIG should be used in the treatment of all ABMR patients, but PP, rituximab, and ATG should be used in selected cases. ABMR has a poor prognosis and treatment should be individualized.

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Risk Factors of Rejection in Renal Transplant Recipients: A Narrative Review.

Multiple factors influence graft rejection after kidney transplantation. Pre-operative factors affecting graft function and survival include donor and recipient characteristics such as age, gender, race, and immunologic compatibility. In addition, several peri- and post-operative parameters affect graft function and rejection, such as cold and warm ischemia times, and post-operative immunosuppressive treatment. Exposure to non-self-human leucocyte antigens (HLAs) prior to transplantation up-regulates the recipient’s immune system. A higher rate of acute rejection is observed in transplant recipients with a history of pregnancies or significant exposure to blood products because these patients have higher panel reactive antibody (PRA) levels. Identifying these risk factors will help physicians to reduce the risk of allograft rejection, thereby promoting graft survival. In the current review, we summarize the existing literature on donor- and recipient-related risk factors of graft rejection and graft loss following kidney transplantation.

Does Tacrolimus Use Have a Sexual Dysfunctional Effect in Women After Renal Transplant?

Tacrolimus, one of the immunosuppressive agents, is used to prevent tissue rejection in renal transplant recipients, but the relationship between the plasma concentrations of tacrolimus and female sexual dysfunction has not yet been elucidated. The aim of this study was to determine the effect of tacrolimus use on sexual dysfunction of women after renal transplant. Twenty-one female patients who successfully underwent transplant and were treated with tacrolimus were enrolled as the patient group, while 21 patients presented to the obstetrics and gynecology clinic for different reasons were included in the study as the control group. The Beck Depression Inventory, Beck Anxiety Inventory, and Female Sexual Function Index were applied. Plasma concentrations of tacrolimus were simultaneously measured in transplant recipients. The scores of all scales did not differ among groups in terms of depression, anxiety, and sexual dysfunction. All transplant recipients had a plasma concentration of tacrolimus in the range of 3 to 7 ng/L. When the patients were compared by the scores of depression and anxiety scales, the drug levels showed no effect on the depression, anxiety, and female sexual functions. Sexual dysfunction appears to be ameliorated in women because of the hormone levels after renal transplant at the end of the dialysis process, hence enhancing the quality of life. Normal plasma levels of tacrolimus, which is known to cause sexual dysfunction, could not change this result.

Does the cytomegalovirus infection cause kidney transplant rejection in Erbil city patients, Kurdistan region of Iraq?

Does the cytomegalovirus infection cause kidney transplant rejection in Erbil city patients, Kurdistan region of Iraq?

Incorporation of Donor-derived Cell-free DNA Into Clinical Practice for Renal Allograft Management

Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)-based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result-matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients.

MO065DIAGNOSTIC CRITERIA OF HUMORAL REJECTION IN RENAL TRANSPLANT RECIPIENTS WITH PRE-EXISTING ANTI-HLA ANTIBODIES BASED ON SENTINEL SKIN FLAP BIOPSY

Abstract Background and Aims Twenty years of transplantation of composite vascularised allografts have revealed the high immunogenicity of the constituent parts, especially the skin.Several researchers have proposed the use of vascular stalk flaps, which allow to performe skin biopsy and diagnose rejection without biopsy of the transplanted solid organ.Pre-existing anti-HLA antibodies represent a serious immunological barrier to successful kidney transplantation.We are not aware of any studies on the diagnosis of antibody-associated acute kidney allograft rejection from deceased donors in recipients with pre-existing antibodies, based on morphological examination of a sentinel skin flap on a vascular stalk. The Aim: To determine the morphological features of humoral rejection in renal transplant recipients with pre-existing anti-HLA antibodies based on sentinel skin flap biopsy. Method Three skin-kidney allografts recipients underwent skin flap biopsy on 2nd day after transplantation. A kidney allograft biopsy was performed on day 7, 30, 60, 90.The results of morphological studies are presented using the Banff classification of renal allograft and skin allograft pathology. All recipients were female; 35, 44, and 57 years old. Two patients were re-transplanted and the main cause of CKD was chronic glomerulonephritis. The third patient, with congenital abnormality of the urinary tract, received her first graft.Pre-existing anti-HLA antibody levels before transplantation were 50%, 60%, 80%, respectively. Results All recipients showed signs of humoral rejection of the skin flap with thrombosis of the feeding vascular bundle, phlebitis, predominantly intimal arteritis with median necrosis, detachment and areactive necrosis of epidermis and epithelium of skin appendages. Clinical rejection, similar to the algorithm proposed by Etra J.W. et al. to assess preclinical skin rejection in an animal model (2019), was interpreted as G2 in two cases and G3 in one case. The Banff classification of the skin flap offers a qualitative assessment of certain biopsy parameters, while the kidney graft has qualitative-quantitative criteria for assessing rejection. When comparing the two classifications, a quantitative gradation of pathological changes in the skin flap according to the parameter of intimal arteritis (v) and immunoreactivity of the C4d marker similar to renal rejection was possible. In histological examination of skin flap biopsies, the degree of vasculitis was assessed in a large feeding artery: in all three cases this parameter was equal to v3. C4d expression was analyzed in the endothelium of microcirculatory blood vessels of the dermis and hypodermis: C4d1 in one case and C4d3 in the other two. The analysis of renal allograft biopsies revealed signs of humoral rejection (v1) only at day 30 in two recipients whose C4d expression in the skin and hypodermis was strong (C4d3). Conclusion Antibody-mediated rejection of a vascularized sentinel skin flap in recipients with combined skin-kidney transplantation is characterized by vasculitis affecting a core vascular bundle in the form of endarteritis with necrosis of media,phlebitis and associated thrombosis.Further studies are required to determine the feasibility of using a vascular stalked skin flap in the diagnosis of humoral rejection after renal transplantation.

Update on Treatment and Prevention of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

Chronic antibody mediated rejection (AMR) is a major cause of allograft failure1,2. Chronic AMR clinically presents with proteinuria and gradual decline in renal function. The underlying mechanisms of AMR include both antibody mediated complement-dependent cytotoxicity, complement-independent cellular cytotoxicity and other mechanisms. The purpose of this review is to appraise recent literature on diagnosis, treatment and prevention of chronic AMR.

P1613INFLUENCE OF GENETIC POLYMORPHISM IN MMPS AND TIMPS ON ALLOGRAFT OUTCOME IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Renal transplantation (RT) is currently the most effective replacement therapy and believed as a boon for patients with end-stage renal disease (ESRD). Allograft rejection remains to be one of the crucial impediments in successful renal transplantation. Matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMPs) play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The study of MMPs and TIMPs in transplant rejection may also lead to novel approaches in the therapy of rejection processes. To investigate the association of functional polymorphisms in MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T gene with risk of allograft rejection in renal transplant recipients of North India. Method A total of two hundred live related renal transplant donors and recipients pairs blood sample was collected and were genotyped for MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G); MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A); TIMP1(+536 C/T) and TIMP3(-1298 C/T) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) methodology. All two hundred renal transplant recipients were categorized into 162 non-rejecters and 32 rejecters and were analyzed further. All the statistical analysis was done using SPSS software. Results The genotype frequencies of MMP1 (-1607 1G/2G) [2G/2G; odds ratio (OR) = 2.97, 95% confidence intervals (95% CI) = 1.69-5.20, P ≤ 0.05]; MMP9 (Q279R) [RQ; odds ratio (OR) = 0.47, 95% confidence intervals (95% CI) = 0.25-0.99, P = 0.02 &amp; QQ; odds ratio (OR) = 0.49, 95% confidence intervals (95% CI) = 0.25-0.94, P = 0.03]; MMP9 (P574R) [PR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.77-4.13, P ≤ 0.05 &amp; RR; odds ratio (OR) = 2.70, 95% confidence intervals (95% CI) = 1.09-6.71, P = 0.03]; TIMP1(+536 C/T) [CT; odds ratio (OR) = 15.41, 95% confidence intervals (95% CI) = 9.12-26.05, P ≤ 0.05 &amp; TT; odds ratio (OR) = 7.01, 95% confidence intervals (95% CI) = 3.39-14.49, P ≤ 0.05] and TIMP3(-1298 C/T) [CT; odds ratio (OR) = 0.31, 95% confidence intervals (95% CI) = 0.19-0.50, P ≤ 0.05] was significantly associated with allograft rejection. On comparison of genotypic frequencies for MMP-1, MMP-3, MMP-9, TIMP1 and TIMP3 gene polymorphisms between rejecters and non-rejecters no significant difference was found while comparing genotypic frequencies of non-rejecters with donors a significant association was observed in MMP1 (-1607 1G/2G) [P ≤ 0.05]; MMP9 (Q279R) [P = 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP 3 [P ≤ 0.05] respectively. Therefore, MMP1 (-1607 1G/2G), MMP9 (Q279R), MMP9 (P574R), TIMP1 and TIMP3 demonstrated significantly reduced risk for allograft rejection. MMP1 (-1607 1G/2G) [P ≤ 0.02]; MMP9 (P574R) [P ≤ 0.05]; TIMP1 [P ≤ 0.05] and TIMP3 [P =0.01] was also found significantly associated on comparison between rejecters and donors. Conclusion Mutant genotypes/ alleles for MMP1 (-1607 1G/2G); MMP9 (Q279R); MMP9 (P574R); TIMP1 (+536 C/T) and TIMP3 (-1298 C/T) are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.

Comparison of prophylactic versus preemptive treatments in the management of cytomegalovirus infection in renal transplant recipients

To prevent acute or chronic rejection in renal transplant recipients, immunosuppressive treatments are applied. However, immunosuppressive treatments increase the risk of cytomegalovirus (CMV) infection. The aim of this study was to evaluate the differences in efficacy and cost of prophylactic and preemptive treatment strategies applied in respect of CMV infection to renal transplant recipients.&#x0D; Methods. Patients who underwent renal transplantation in our center between 2010 and 2015, were retrospectively analyzed. The patients were allocated in two groups as those who received prophylaxis or preemptive treatment. A record was made of the kidney function tests (KFT), CMV PCR copy numbers, the presence of CMV infection, antiviral treatments received, and the costs were calculated of the tests and treatments. The groups were compared in respect of CMV infection and costs.&#x0D; Results. A total of 71 patients with a median age of 38 years (range, 19-74 years) were included in the study. The prophylaxis group included 43 patients and the preemptive group included 28 patients. CMV infection was detected in 7 (16.3%) of the prophylaxis group and 2 (7.1%) patients of the preemptive group (p=0.467). The cost per month of the tests and treatment was lower in the preemptive group than in the prophylaxis group (p&lt;0.001).&#x0D; Conclusion. No significant difference was determined between the prophylactic and preemptive treatment protocols in respect of the CMV infection in the intermediate-risk group renal transplantation recipients. Preemptive treatment was seen to be a more cost-effective method than prophylactic treatment in Turkey.

An intronic polymorphism of NFATC1 gene shows a risk association with biopsy-proven acute rejection in renal transplant recipients.

BackgroundWe aimed to explore the influence of single nucleotide polymorphisms (SNPs) in NFATC1 gene on the occurrence of biopsy-proven acute rejection (BPAR) in renal transplant recipients.MethodsBlood samples from 131 subjects with stable allograft function (STA) and 69 with BPAR episodes were collected and analyzed using target sequencing (TS) with an established panel. Odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated for logistic regression models adjusted for confounding factors. Pathological changes were extracted and the relationship with tagger SNPs was calculated. Moreover, the CCK-8 assay was performed to explore the proliferation of T lymphocytes, and PCR, Western blotting and enzyme-linked immunosorbent assay were applied to identify the effect of mutant on the activation of T cells.ResultsHigh-quality readouts were obtained for 55 NFATC1 SNPs and 14 tagger SNPs were remained for further analysis. After adjusting for clinical confounding factors, the distribution of four NFATC1 SNPs, including rs2290154, rs2304738, rs754093 and rs754096, were statistically significant between STA and BPAR groups. Pathological association analysis indicated one SNP, rs2290154, was significantly related with the Banff score and renal tubulitis. Our in vitro study suggested that NFATC1 rs2290154 mutant could remarkably promote the T cell proliferation, increase the transcription of NFATC1 mRNA and expression of NFATC1 protein, as well as the interleukin-2 (IL-2) secretion.ConclusionsWe reported the crucial association of NFATC1 gene with the occurrence of acute rejection (AR) episodes. Moreover, in vitro NFATC1 rs2290154 was significantly involved in the T lymphocytes activation and proliferation through increasing the translation of NFATC1 mRNA and expression of NFATC1 protein, along with the secretion of IL-2.

Treatment of chronic active antibody-mediated rejection in renal transplant recipients \u2013 a single center retrospective study

BackgroundChronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies.MethodsComputerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment.ResultsFrom February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis.ConclusionsAggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.