Risk Of Acute Rejection Research Articles

The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients.

The longitudinal relationship between HLA class I and II eplet mismatches, de novo donor-specific antibodies (dnDSA) development, and acute rejection after transplantation in childhood is unknown. Eplet mismatches at HLA class I and II loci were calculated retrospectively for each donor/recipient pair transplanted between 2005 and 2015 at a single Australian center. Logistic regression analyses were conducted to determine the association between the number of eplet mismatches, dnDSA, and acute rejection. The cohort comprised 59 children (aged 0-18years) who received their first kidney allograft and were followed for median (interquartile range) 4.5 (± 2.6) years. Overall, 32% (19/59) developed dnDSA (class I 3% (2/59), class II 14% (8/59), 15% class I and II (9/59)), and 24% (14/59) developed biopsy-proven acute rejection. Every unit increase in class I and II eplet mismatches corresponded to an increase in risk of class I (odds ratio (OR) 1.22, 95% CI 1.07-1.39, p < 0.01) and class II (OR 1.06, 95% CI 1.01-1.11, p = 0.02) dnDSA development. Compared with recipients without dnDSA, class I and II dnDSA were associated with direction of effect towards increased risk of acute cellular rejection (class I: OR 5.87, 95% CI 0.99-34.94, p = 0.05; class II: OR 12.00, 95% CI 1.25-115.36, p = 0.03) and acute antibody-mediated rejection (class I: OR 25.67, 95% CI 3.54-186.10, p < 0.01; class II: OR 9.71, 95% CI 1.64-57.72, p = 0.01). Increasing numbers of HLA class I or II eplet mismatches were associated with the development of dnDSA. Children who developed dnDSA were also more likely to develop acute rejection compared with children without dnDSA.

Immunosuppression in Kidney Transplantation

Immunosuppressive therapy in renal transplantation is divided into two phases as induction and maintenance therapy. Induction therapy is an intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, induction immunosuppressive strategies utilized by kidney transplant centers fall in one of the two categories. One approach relies upon high doses of conventional immunosuppressive agents, while the other uses antibodies directed against T-cell antigens with lower doses of conventional agents. Maintenance immunosuppressive therapy is administered to almost all kidney transplant recipients to help prevent acute rejection and the loss of renal allograft. Although an adequate level of immunosuppression is required to dampen the immune response, the level of chronic immunosuppression is decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy; these risks directly correlate with the degree of overall immunosuppression. However, the optimal maintenance immunosuppressive therapy in kidney transplantation is not established. The major immunosuppressive agents that are available in various combination regimens are glucocorticoids (primarilyoral prednisone), azathioprine, mycophenolate mofetil (MMF), enteric-coated mycophenolate sodium (EC-MPS), cyclosporine (unmodified or modified [micro emulsion] form), tacrolimus, everolimus, rapamycin (sirolimus), and belatacept.

The value of high-resolution HLA in the perioperative period of non-sensitized lung transplant recipients.

The importance of HLA antigen matching is widely recognized and accepted worldwide. With the improvement of diagnostic methods, recent studies have shown that eplet mismatched for organ transplantation is essential. In the field of lung transplantation, eplet mismatch (MM) is closely related to chronic rejection after lung transplantation. To further investigate the relationship between early graft failure and acute rejection, we performed high-resolution HLA analysis on 59 patients in our center. We conduct high-resolution HLA matching and Donor specific antibody (DSA) monitoring on 59 lung transplantation donors and recipients from April 1, 2018, to June 30, 2019. Baseline data were collected composed of both recipient characteristics and transplant-related features. Clinical outcomes were primary graft dysfunction (PGD) and acute rejection (AR). Overall, for these 59 patients, HLA antigen mismatch is 7.19±1.61, eplet mismatch is 8.31±1.75 (P=0.0005). As the number of mismatch sites increases, the severity of PGD increased significantly, especially when presented both eplet mismatch and HLA-DQ mismatch. In this group of patients, 2 cases of antibody-mediated rejection (AMR) occurred after transplantation, eplet MM 9 (HLA-DQ MM 2) and eplet MM 5 (HLA-DQ MM1). Both patients developed DSA after operation, and they are DQB1 06:01 and C07:02, respectively. There were 9 cases of death during the perioperative period. Five of them died of severe PGD, and 4 died of severe infection. All these 9 patients were with high-level eplet MM and HLA-DQ MM. Perioperative PGD and AR closely related to HLA mismatches, especially eplet and HLA-DQ MM. It might be noteworthy to do complementary detection of eplet matching and DSA in lung transplant donors and recipients, to predict the risk of early PGD and acute rejection after lung transplantation.

Nuclear factor of activated T cells as potential pharmacodynamic biomarker for the risk of acute and subclinical rejection in de novo liver recipients.

Nuclear factor of activated T cell-regulated gene expression (NFAT-RGE) has been proposed as a pharmacodynamic biomarker for tacrolimus (Tac) and cyclosporine (CsA). Our aim was to evaluate the role of NFAT-RGE in modulating intralymphocytary IL-2 and IFN-γ expression and its clinical utility as an early non-invasive predictive biomarker for the risk of acute rejection (AR) and infection in de novo liver transplant (LT) recipients. Fifty-six LT recipients treated with Tac or CsA [with and without mycophenolate mofetil (MMF)] were included: 30 free of rejection or infection, 11 rejectors (T cell-mediated acute rejection), 5 with subclinical rejection (SCR) and 10 with cytomegalovirus (CMV) infection. Within the first 3months after transplantation, NFAT-RGE of IL-2, IFN-γ and GM-CSF and intralymphocytary synthesis of IL-2 and IFN-γ were evaluated by real-time PCR and flow cytometry respectively. A significant increase in NFAT-RGE was observed in patients who experienced TCMAR (75% [42-100%]) or SCR (41% [18-78%]) compared with patients without rejection or infection (14% [2-23%]). Positive correlations between the %NFAT-RGE-IFN and both the %CD8CD69IFN-γ and %CD4CD69IFN-γ and between the %NFAT-RGE-IL2 and the %CD8CD69IL2 were observed. NFAT-RGE was significantly lower in CMV+ patients than in non-infected patients. Finally, an inverse correlation between the Tac or CsA concentration and inhibition of NFAT-RGE were observed. Sequential post-transplantation NFAT-RGE monitoring combined with intralymphocytary IL-2 and IFN-γ before transplantation and at the first and third month post-transplantation may be key predictive and diagnostic biomarkers for the risk of TCMAR and SCR and better guide CNi therapy in LT patients.

The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis.

Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Efficacy of anti-T-lymphocyte globulin-Fresenius as an induction agent in deceased-donor renal transplantation: A cohort study.

Anti-T-lymphocyte globulin (ATG) is frequently used in the induction regimen of renal transplantation, but its dose has not been standardized. In the present study, the efficacy of different ATG-Fresenius (ATG-F) doses was assessed in recipients of renal transplantation. A total of 131 adult recipients of renal transplantation who received ATG-F induction between August 2015 and July 2018 were included. The incidence of biopsy-confirmed acute rejection, graft function, as well as graft and patient survival within 12 months post-transplant, was assessed, and adverse events, including hematologic and infection-associated side effects, were compared between patients receiving a cumulative ATG-F dose of <7 or ≥7 mg/kg. The incidence of biopsy-confirmed acute rejection was similar between patients receiving cumulative doses of <7 and ≥7 mg/kg (7.5 vs. 4.7%, P=0.766). The incidence of infection within 12 months was lower in the ATG-F <7 mg/kg group compared with that in the ≥7 mg/kg group (26.9 vs. 50.0%, P=0.006), but the incidence of pneumonia did not differ between the ATG-F <7 and ≥7 mg/kg groups (10.4 vs. 20.3%, P=0.117). The incidence of urinary infection was higher in the ≥7 mg/kg group than in the <7 mg/kg group (20.4 vs. 7.46%, P=0.033), while the extent and duration of anemia and lymphopenia was similar between groups. There was no difference in graft function, delayed graft function, as well as overall and graft survival between the groups. In conclusion, a moderate reduction in the cumulative ATG-F dose was not associated with an increased risk of acute rejection, while the risk of infection was reduced. Optimization of the ATG-F dose for induction may facilitate the reduction of the risk of infection without compromising the induction efficacy in renal transplant recipients.

Variable Benefits of Antibody Induction by Kidney Allograft Type

BackgroundKidneys from acute renal failure (ARF), expanded criteria donors (ECD), and donation after cardiac death (DCD) donors are often discarded due to concerns for delayed graft function (DGF) and graft failure. Induction immunosuppression may be used to minimize these risks, but practices vary widely. Furthermore, little is known regarding national outcomes of transplant recipients receiving induction immunosuppression for receipt of high-risk kidneys. Materials and methodsUsing a center-level retrospective study, deceased donor transplants (115,485) from the Scientific Registry of Transplant Recipients from January 2003 to June 2016 were evaluated. Patients who received induction immunosuppression, including lymphocyte immune globulin, muromonab CD-3, IL-1 receptor antagonist, anti-thymocyte globulin, daclizumab, basiliximab, alemtuzumab, and rituximab, were included. Associations of center-level induction use with acute rejection in the first post-transplant year, graft failure, and patient mortality were evaluated using multivariable Cox and logistic regression. ResultsAmong all kidneys, increasing percentage of center-level induction was associated with lower risk of graft failure, acute rejection, and patient mortality. In recipients of ARF kidneys, the beneficial association of induction on graft failure and acute rejection was greater than in those that received non-ARF kidneys. Marginally greater benefit of induction was seen for acute rejection in ECD compared to standard criteria donor (SCD) recipients and for graft failure in DCD compared to donors after brain death (DBD). No benefit of induction was detected for patient and graft survival in ECD recipients, acute rejection in DCD recipients, and patient survival in DGF recipients. No difference in the benefit of induction was detected in any other comparisons. ConclusionsWhile seemingly beneficial for recipients of all kidneys, induction has more robust associations with lower graft failure and acute rejection probability for recipients of ARF kidneys. Given the lack of observed benefit for ECD recipients, induction policies should be carefully considered in these patients.

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Renal Transplant Outcomes in Spousal and Living-Related Donors in Malaysia

Studies have shown that a compatible human leukocyte antigen (HLA) match can confer a favourable effect on graft outcomes. We examined the outcomes of HLA matching in renal transplant donors in Malaysia. A total of 140 patients who had compatible ABO blood type with negative T-cell lymphocytotoxicity crossmatch were included in the study and 25% of them were spousal transplant donors. No remarkable differences in acute rejection rate, graft survival, patient survival and serum creatinine level were observed between the spousal and living-related donor groups. The spousal donor group had a higher degree of HLA mismatch than the living-related donor group. HLA-A mismatch was associated with increased rejection risk at 6 months (odds ratio [OR], 2.75; P = 0.04), 1 year (OR, 2.54; P = 0.03) and 3 years (OR, 3.69; P = 0.001). It was also observed in the deleterious effects of HLA-B and HLA-DQ loci when the number of antigen mismatches increased. The risk was 7 times higher in patients with ≥1 mismatch at HLA-A, HLA-B and HLA-DR loci than those who did not have a mismatch at these loci at 6 months (P = 0.01), 1 year (P = 0.03) and 3 years (P = 0.003). A good match for HLA-A, HLA-B, HLA-DR and HLA-DQ can prevent acute rejection risk in renal transplant patients. Consequently, spousal donor transplants could be a safe intervention in renal patients.

Maladie rénale chronique et immunosénescence prématurée : données et perspectives

Immune senescence is associated with age-related diseases (i.e. infectious disease, cardiovascular diseases and cancers). Chronic kidney disease patients die prematurely when compared with general population, because of a higher occurrence of infections, cardiovascular events and cancer. These diseases are commonly observed in the elderly population and frequently associated with immune senescence. Indeed, chronic kidney disease causes a premature aging of the T lymphocyte compartment, widely related to a decrease in thymic function, a phenomenon that plays a key role in the onset of age-related diseases in chronic kidney disease patients. The degree of immune senescence also influences patients’ outcome after renal transplantation, particularly the risk of acute rejection and infections. Partial reversion of pre-transplant immune senescence is observed for some renal transplant patients. In conclusion, to reduce the increasing incidence of morbidity and mortality of chronic kidney disease patients, a better knowledge of uremia-induced immune senescence would help to pave the way to build clinical studies and promote innovative therapeutic approaches. We believe that therapeutic reversion and immune senescence prevention approaches will be part of the management of chronic kidney disease patients in the future.

Systematic review and meta-analysis of asymptomatic bacteriuria after renal transplantation: incidence, risk of complications, and treatment outcomes.

Routine treatment for asymptomatic bacteriuria (ASB) after renal transplantation (RT) represents nowadays a controversial topic, being unknown its impact on the overall prognosis of the transplanted patient. Studies published during 1970-2019 that evaluated the benefit of treating ASB after RT regarding the risk of renal complications were included. The primary outcome was to assess whether the treatment is associated with a lower risk of symptomatic urinary tract infection (UTI) or an improved renal function at the end of the follow-up period. The secondary outcome was the risk of acute graft rejection (AGR). A meta-analysis with a random-effect model was performed. Heterogeneity was assessed with the I2 measure. Fifteen studies were included. The incidence of ASB in the first month and the first year after RT was 22% and 30%, respectively. ASB was not correlated to AGR (OR 1.18; 95% CI, 0.78-1.79). Eight studies compared the outcomes of ASB treatment, finding no benefit of treating regarding the risk of symptomatic UTI (OR 1.08; 95% CI, 0.63-1.84; I2 =35%) or the change in renal function (mean difference in serum creatinine concentration-0.03mg/dL,95% CI-0.15-0.10; I2 =53%). Asymptomatic bacteriuria represents a frequent finding after RT, highlighting the need for appropriate management of this condition. Considering that its treatment did not decrease the risk of the studied complications, antibiotic therapy should start to be questioned, as it has been related to higher rates of antimicrobial resistance and high economic costs.

Assessment of rejection risk following subtherapeutic calcineurin inhibitor levels after pediatric heart transplantation.

CNIs are the mainstay of immunosuppressive therapy after pediatric HTx. While regular laboratory surveillance is performed to ensure blood levels are within targeted range, the risk of acute rejection associated with subtherapeutic CNI levels has never been quantified. This is a retrospective single-center review of 8413 CNI trough levels in 138 pediatric HTx recipients who survived >1year after HTx. Subtherapeutic CNI levels were defined as <50% of the lower limit of target range. The risk of acute, late (>12months post-transplant) rejection following recipients' subtherapeutic CNI levels was assessed using time-varying multivariable Cox proportional hazards analysis. We found that 79 of 138 recipients (57%) had at least one subtherapeutic CNI level on routine surveillance laboratories during a mean follow-up of 5.5±3.6years. Following an episode of subtherapeutic levels, 17 recipients (22%) had biopsy-proven rejection within the next 3months; the majority (9/17) within the first 2weeks. After presenting with subtherapeutic CNI levels, recipients incurred a 6.1 times increased risk of acute rejection in the following 3months (HR=6.11 [2.41, 15.51], P=<.001). Age at HTx, HLA sensitization, or positive crossmatch were not associated with acute late rejection, but rejection in the first post-transplant year was (HR 2.61 [1.27, 5.35], P=.009). Thus, maintaining therapeutic CNI levels is the most important factor in preventing acute rejectionin recipients who are >12months after pediatric HTx. Recipients who present with subtherapeutic CNI levels on surveillance monitoring are 6.1 times more likely to develop rejection in the following 3months.

Blood proteome profiling using aptamer-based technology for rejection biomarker discovery in transplantation

Face transplantation is a promising solution for patients with devastating facial injuries who lack other satisfactory treatment options. At the same time, this type of transplantation is accompanied with high risks of acute transplant rejection. The limitations of traditional skin biopsy and the need to frequently monitor the condition of face transplant call for less invasive biomarkers to better diagnose and treat acute rejection. Discovery of peripheral serum proteins accurately reflecting the transplant status would represent a reasonable solution to meet this demand. However, to date, there is no clinical data available to address the feasibility of this approach. In this study, we used the next generation aptamer-based SOMAscan proteomics platform to profile 1305 proteins of peripheral blood serum in twenty-four samples taken from 6 patients during no-rejection, nonsevere rejection, and severe rejection episodes. Also, we provide a detailed description of biosample processing and all steps to generate and analyze the SOMAscan dataset with hope it will assist in performing biomarker discovery in other transplantation centers using this platform.

A Single-Nucleotide Polymorphism (rs1131243) of the Transforming Growth Factor Beta Signaling Pathway Contributes to Risk of Acute Rejection in Chinese Renal Transplant Recipients.

BackgroundAcute rejection (AR) is a common complication of kidney transplantation. The transforming growth factor beta (TGF-β) signaling pathway has been observed to be involved in several cellular functions. Our study aimed to investigate the correlations between single-nucleotide polymorphisms (SNPs) in TGF-β-related genes and the risk of AR in renal transplant recipients.Material/MethodsThis retrospective, single-center study included 200 Chinese renal transplant recipients. All exons, exon/intron boundaries, and flanking regions of the TGF-β signaling pathway were detected by targeting sequencing (TS) based on next-generation sequencing technology. Tagger SNPs and haplotypes were identified after adjustment. A general linear model (GLM) was used to explore the confounding effect of clinical variables. Five adjusted inheritance models were utilized to investigate the influence of SNPs on AR, and Banff score was applied to evaluate the effect of related SNPs on pathological changes.ResultsA total of 188 SNPs on TGF-β genes were detected. Analysis of adjustment led to identification of 31 tagger SNPs and 10 haplotype blocks. After the analysis of a general linear model and 5 sirolimus-adjusted multiple inheritance models, 1 of the SNPs – rs1131243 on the TGF-βR3 gene – was observed to be significantly associated with the occurrence of AR. Based on Banff score, no significant association was observed between SNPs and pathological changes.ConclusionsIn this study, we observed that the SNP rs1131243 on the TGF-βR3 gene was significantly associated with the occurrence of AR in Chinese renal transplant recipients.

Outcome of Liver Transplant Patients With Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies.

After liver transplantation (LT), the role of preformed donor-specific anti-human leukocyteantigen antibodies (pDSAs) remains incompletely understood. We conducted a retrospective, case-control analysis to determine the impact of pDSAs after LT in 3 French transplant centers (Bordeaux, Lyon, and Toulouse). Among the 1788 LTs performed during the study period, 142 (7.9%) had at least 1 pDSA. The patient survival rate was not different between patients who received an LT with pDSAs and the matched-control group. A liver biopsy was performed 1year after transplantation in 87 recipients. The metavir fibrosis score did not differ between both groups (1±0.8 versus 0±0.8; P=0.80). However, undergoing a retransplantation (hazard ratio [HR]=2.6, 95% confidence interval [CI], 1.02-6.77; P=0.05) and receiving induction therapy with polyclonal antibodies (HR=2.5; 95% CI, 1.33-4.74; P=0.01) were associated with a higher risk of mortality. Nonetheless, high mean fluorescence intensity (MFI) donor-specific antibodies (ie, >10,000 with One Lambda assay or >5000 with Immucor assay) were associated with an increased risk of acute rejection (HR=2.0; 95% CI, 1.12-3.49; P=0.02). Acute antibody-mediated rejection was diagnosed in 10 patients: 8 recipients were alive 34 (1-125) months after rejection. The use of polyclonal antibodies or rituximab as an induction therapy did not reduce the risk of acute rejection, but it increased the risk of infectious complications. In conclusion, high MFI pDSAs increase the risk of graft rejection after LT, but they do not reduce medium-term and longterm patient survival. The use of a T or B cell-depleting agent did not reduce the risk of acute rejection.

Costimulation Blockade in Kidney Transplant Recipients.

Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.

Fat soluble vitamins deficiency in pediatric chronic liver disease: The impact of liver transplantation

BackgroundChildren affected with chronic liver disease are at risk for fat-soluble vitamins (FSV) deficiency, in this scenario the role of liver transplant has been only partially explored. AimsThis study aimed to evaluate the prevalence of FSV deficiency in a cohort of paediatric patients awaiting liver transplant, analyze relationships between plasma vitamin concentrations and risk of acute rejections and liver fibrosis and assess the impact of the transplant on vitamin status. Methods166 children candidates for liver transplant were retrospectively evaluated. Vitamin concentrations were measured before and 12 months after transplantation. ResultsBefore transplant vitamin A, vitamin E and vitamin D deficiency was found in 66.6%, 40.6% and 36.3% of patients, respectively. 12 months after surgery, the prevalence of deficiency decreased to 29,5% and 2,6% for vitamin A and E while remained the same for vitamin D (36.3%). No association was found between vitamin status and the risk of acute rejections or the severity of liver fibrosis. ConclusionLiver transplant was effective to improve vitamin A and E, but it did not affect vitamin D. A consensus is needed to define optimal nutritional management of these patients in order to prevent deficiencies.

Polymorphisms in vasoactive eicosanoid genes of kidney donors affect biopsy scores and clinical outcomes in renal transplantation.

Cytochrome P450 (CYP) enzymes metabolize arachidonic acid to vasoactive eicosanoids such as epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), whilst soluble epoxide hydrolase, encoded by the EPHX2 gene, is in charge of EETs degradation. We aimed to analyze the influence of common, functional polymorphisms in four genes of the donor on the renal biopsy scores independently assigned by pathologists. Additionally, we examined whether this score or the presence of these SNPs were independent risk factors of clinical outcomes in the first year after grafting. A cohort of 119 recipients and their corresponding 85 deceased donors were included in the study. Donors were genotyped for the CYP4F2 V433M, CYP2C8*3, CYP2J2*7, EPHX2 3’UTR A>G, EPHX2 K55R and EPHX2 R287Q polymorphisms. The association of the donors’ SNPs with the biopsy scores and clinical outcomes was retrospectively evaluated by multivariate regression analysis. The CYP2C8*3 polymorphism in the donor was significantly associated with higher scores assigned to pretransplant biopsies [OR = 3.35 (1.03–10.93), p = 0.045]. In turn, higher scores were related to an increased risk of acute rejection [OR = 5.28 (1.32–21.13), p = 0.019] and worse glomerular filtration rate (eGFR) (45.68±16.05 vs. 53.04±16.93 ml/min in patients whose grafts had lower scores, p = 0.010) one year after transplant. Patients whose donors carried the CYP4F2 433M variant showed lower eGFR values (48.96±16.89 vs. 55.94±18.62 ml/min in non-carriers, p = 0.038) and higher risk of acute rejection [OR = 6.18 (1.03–37.21), p = 0.047]. The CYP2J2*7 SNP in the donor was associated with elevated risk of delayed graft function [OR = 25.68 (1.52–43.53), p = 0.025]. Our results taken together suggest that donor genetic variability may be used as a predictor of tissue damage in the graft as well as to predict clinical outcomes and graft function in the recipient.

Comparison of low-dose and standard-dose mycophenolate mofetil in kidney transplant patients with delayed graft function

Objective To investigate the effects of different doses of mycophenolate mofetil (MMF) in delayed graft function (DGF) patients in the early stage after kidney transplantation. Methods This one-year, single-center retrospective study was designed to compare complications such as infection and rejection of different doses of MMF in DGF patients in the early stage after kidney transplantation. The DGF patients were divided into two groups according to their oral MMF dose: a standard-dose group (SMDGF, n=17) and a low-dose group (LMDGF, n=16). Thirty non-DGF recipients (NDGF) were selected as a control group during this period. Results The results showed that the glomerulosclerosis rate was an independent risk factor for infection in DGF patients [odds ratio (OR): 0.37; 95% confidence interval (CI): 0.19-0.73; P<0.01]. The infection rate was significantly higher in the SMDGF group than in the NDGF group (58.8% vs. 26.7%, χ2=4.748, P<0.05) and in the LMDGF group (18.8% vs. 58.8%, χ2=5.544, P<0.05). The mycophenolic acid area under curve of the low-dose MMF regimen was within the therapeutic window. The low-dose MMF regimen did not increase the risk of acute rejection in DGF patients. Conclusion For patients with DGF, low-dose MMF reduces the infection rate, while the risk of acute rejection does not increase. Key words: Delayed graft function; Mycophenolate mofetil; Renal biopsy; Kidney transplantation

552 Exploring the Role of Gastrointestinal Motility and Non-Acid Reflux in Lung Transplant Prognosis and Risk of Acute Rejection

INTRODUCTION: Lung transplant patients are at risk of developing acute rejection leading to bronchiolitis obliterans syndrome (BOS). Lung transplant patients are also known to have and/or develop gastroesophageal reflux. Acid gastroesophageal reflux has been correlated with risk of acute rejection and consequently BOS. There is however a paucity of data correlating non-acid reflux with risk of acute rejection. Our study investigated the role of non-acid reflux with lung transplant rejection. METHODS: 131 lung transplant recipients who had post-transplant evaluation between 2012 and 2019 were studied. A total of 64 lung transplant recipients had at least 3 months of post-transplant follow up consisting of 24 hour impedance pH testing, and high-resolution manometry (HREM). Patient characteristics were summarized with counts and percentages, means and SD, or medians and interquartile ranges (IQR) as appropriate to scale and distribution. The characteristics of those with and without rejection diagnoses was compared with Fisher's exact test for categorical variables and the Wilcoxon rank sum test for quantitative variables. Analyses were conducted in the open source R software environment. RESULTS: 60 of 64 patients (94%) were alive at one-year post- lung transplant. The majority of patients had bilateral transplants and were Caucasian males with average age of 59 years. At one year there were 12 deaths. Patients with a diagnosis of acute rejection were less likely to exhibit gastroparesis (1% vs. 9%) and abnormal pH (28% vs. 45%). Acute rejection patients were more likely to exhibit GERD (53% vs. 45%), more non-acid episodes (median 19 vs. 15.5), higher reported symptom association (51% vs. 41%), on impedance pH; abnormal UES (56% vs. 45%), and abnormal body (86% vs. 77%) on HREM (Table 1). However, no differences were statistically significant (all P &gt; .18), and conclusions cannot be generalized. CONCLUSION: Patients undergoing lung transplantation were found to have a high incidence of abnormal gastroesophageal motility studies, including both acid and non-acid reflux. Developing a protocolized pre- and post- transplant motility evaluation process for lung transplant patients may help identify those at greatest risk for acute rejection. Continued evaluation post-transplantation to establish therapeutic interventions in both acid and non-acid reflux patients to prevent lung transplant rejection appears warranted.