Study Of Renal Transplant Recipients Research Articles

Urinary Biomarkers for Cell Cycle Arrest TIMP-2 and IGFBP7 for Prediction of Graft Function Recovery after Kidney Transplantation.

TIMP-2 and IGFBP7 have been identified and validated for the early detection of renal injury in critically ill patients, but data on recovery of allograft function after kidney transplantation (KTx) are scarce. In a prospective observational multicenter cohort study of renal transplant recipients, urinary [TIMP-2] × [IGFBP7] was evaluated daily from day 1 to 7 after KTx. Different stages of early graft function were defined: immediate graft function (IGF) (decrease ≥ 10% in serum creatinine (s-crea) within 24 h post KTx); slow graft function (SGF) (decrease in s-crea < 10% within 24 h post KTx); and delayed graft function (DGF) (any dialysis needed within the first week after KTx). A total of 186 patients were analyzed. [TIMP-2] × [IGFBP7] was significantly elevated as early as day 1 in patients with DGF compared to SGF and IGF. ROC analysis of [TIMP-2] × [IGFBP7] at day 1 post-transplant for event "Non-DGF" revealed a cut-off value of 0.9 (ng/mL)2/1000 with a sensitivity of 87% and a specificity of 71%. The positive predictive value for non-DGF was 93%. [TIMP-2] × [IGFBP7] measured at day 1 after KTx can predict early recovery of transplant function and is therefore a valuable biomarker for clinical decision making.

Renal transplants increase in size and function in keeping with compensatory renal hypertrophy.

To evaluate changes in allograft kidney length in renal transplant recipients and the relationship with estimated glomerular filtration rate (eGFR). This single-centre retrospective study of renal transplant recipients was conducted at Flinders Medical Centre (FMC) from January 2007 to June 2020. Donor and recipient details, renal allograft length from transplant ultrasounds at 0, 1, 3, 6 and 12 months were collected. The association between compensatory renal hypertrophy (CRH) and eGFR and its magnitude was analysed using multivariate multilevel mixed-effects linear regression models. A total of 183 renal transplant recipients were studied. 100 of 175 recipients (62.9%) demonstrated an increase in renal length defined as any increase in maximal longitudinal diameter on serial ultrasounds. Twenty-three recipients (13.1%) had no change in transplant length and 42 recipients (24%) had a decrease in length. The mean increase in kidney length over the first 12 months was 0.57 cm. Ninety of 156 (57.7%) recipients with a renal ultrasound within a month post-transplant demonstrated a mean increase kidney length of 0.3 cm. Multivariate analysis demonstrated that eGFR increased by 2.5 mL/min/1.73 m2 (95% CI 0.72- 4.4; p = .006) with every 1 cm increase in kidney length. Absolute changes in kidney length did not demonstrate any statistically significant correlation with eGFR in both complete case and multiple imputation analysis. An increase in transplant kidney length is common in renal transplant recipients and is associated with enhanced eGFR. However, further studies need to be performed to study the association of absolute change in kidney length and eGFR.

Spectrum of COVID-19 infections in renal transplant recipients: A single-center case series

Objective: COVID-19 infection can be mild to devastating in renal transplant recipients. We looked at the clinical course in all the renal transplant recipients who attended our hospital for COVID-19 infection. Study Design: Case series - This was a retrospective observational study of renal transplant recipients infected with varying degrees of COVID-19 infection, who sought care in our hospital. COVID-19 infection was defined as mild, moderate, or severe based on the guidelines issued by the Ministry of Health and Family Welfare, Government of India. Settings and Participants: The study included all renal transplant recipients with a functioning graft, who attended our hospital for COVID-19 infection between July 2020 and January 2022. Their data were obtained from electronic records. Results and Observations: A total of 18 renal transplant recipients sought care at our center for COVID-19 infection. There were 19 episodes of COVID infection in these 18 patients (one reinfection). Seven of these were transplanted at our center and 11 were transplanted elsewhere and were following up at our center. Of the 18 patients, 12 (66.67%) had mild infection, 2 (11.11%) had moderate COVID-19 infection, and 4 (22.22%) had severe or critical disease. Two of the severe cases died with a functioning graft, one had graft loss, and one recovered. Acute kidney injury occurred in 22.22% of cases (n = 4). The most common presenting symptom was fever (77.78%). The most common comorbidity was hypertension. The source of infection was predominantly the community (17/18 patients). The number of renal transplants during the above period at our center was 24. The infection rate and mortality rate among these patients were 29.16% (n = 7) and 42/1000 (n = 1), respectively. Limitations: The study was based on the availability of data in our electronic records. There was no standard immunosuppression protocol followed. The retrospective design and small numbers are added limitations of our study. As we included all renal transplant recipients with COVID-19 infection irrespective of the time and place of transplant, the infection rate and mortality rate could not be computed on all 18 patients using a common denominator. Conclusion: Transplant patients have a variable outcome after COVID-19 infection. There may be an inherent individual susceptibility in addition to risk factors such as immunocompromised state and diabetes.

Quantification of belatacept by liquid chromatography-tandem mass spectrometry in human plasma: Application to a pharmacokinetic study in renal transplant recipients

Therapeutic drug monitoring is the cornerstone of immunosuppressive treatment in transplantation. The immunosuppressive drugs used in kidney transplant patients are mostly comprised of biologics, including therapeutic monoclonal antibodies (mAbs) and fusion proteins. Therefore, a specific and sensitive analytical technique that can universally quantify mAbs, as well as fusion proteins, is essential for clinical pharmacokinetics studies.In this short communication, we describe the validation of a liquid chromatography tandem mass-spectrometry (LC-MS/MS) method for quantification of the fusion protein belatacept in the plasma of kidney-transplant patients. Sample preparation was based on our previously published and implementable electrospray ionization LC-MS/MS method that allows the simultaneous quantification of seven mAbs. Immunocapture was made possible by the Fc domain of belatacept and identification/quantification by the choice of MRM transitions of peptides. The temporal evolution of the belatacept concentration after intravenous infusion and inter-individual variability of trough concentrations were assessed in 17 human plasma samples.The belatacept calibration curves were linear from 1 to 200 mg.L−1 and within-day and between-day accuracy and precision fulfilled Food and Drug Administration validation criteria. Residual belatacept concentrations (n = 8) ranged from 5.1 to 15.0 mg.L−1, with a median of 8.9 mg.L−1 and an inter-individual CV of 33.0%.Our generic LC-MS/MS method allows the quantification of fusion proteins, such as belatacept, and could be used for therapeutic drug monitoring. This method provides a useful tool to study the intra-patient variability of belatacept and the association between belatacept exposure and its therapeutic effects.

342.9: Factors Associated With a Higher Need for Antihypertensive Medications at 12- Months Post Renal Transplantation

Background: Hypertension (HTN) after renal transplantation can be difficult to control and often requires multiple blood pressure (BP) medications. In this study we examined the incidence and risk factors of “difficult to treat HTN” at one year post kidney transplantation at our center. Method: A single center retrospective study of renal transplant recipients who underwent kidney transplantation between January 2017 and May 2020 with 12 months follow up. We reviewed patients’ demographics, results of pretransplant cardiovascular imaging, and the change of cardiovascular risk factors during the first-year post kidney transplantation. We divided patients according to the number of their blood pressure medications at one year into two groups; those who required none or one, and those who required two or more medications. We labeled those who required ≥2 as “difficult to treat hypertension”. The target BP during the time of this retrospective study was <140/90 mm Hg as per the published guidelines during the time of the study.1 Results: A total of 278 renal transplant recipients were included. The majority (74%) was ≥ 30 years, 58% were men and 80% were living-donor kidney recipients. Preemptive transplantation was 10.1%. PD and HD were 11.5% and 78.4%, respectively. At one year, 70.1% of the patients attained to the target BP goal. Of the total study population; (N: 105, 38%) required ≥ 2 BP medications (i.e., “difficult to treat HTN”). Factors related to a higher need for antihypertensive medications included age (50 vs. 39 years, P<0.001), prior history of hypertension (P=0.006), prior AV fistula vs. dialysis catheter (P=0.044) and diabetes mellitus (P<0.001). Dialysis vintage (including preemptive transplantation), type of dialysis (HD vs. PD), type of transplant (living donor kidney transplant vs deceased donor kidney transplant), and smoking were not different among the two groups. Patients with “difficult to treat HTN” at one year were more likely to have abnormal pre-transplant cardiovascular baseline imaging including abnormal ejection fraction <55% (P=0.044), abnormal wall motion on echocardiography (P=0.004), abnormal perfusion stress test (P<0.001), higher calcium scoring (P=0.002), abnormal cardiac catheterization (P<0.001), and a higher degree of calcifications on CT of pelvic arteries (P=0.006). Patients with “difficult to treat HTN” at one year were likely to have a higher BMI at 12 months (P=0.028) whereas rejection, change of creatinine, weight gain, persistent hyperparathyroidism or anemia at 12 months were not different among the two groups. Multivariate analysis of requiring ≥1 BP medication indicated a relation with age (aOR: 1.025, CI: 1.003-1.048, P=0.026); male vs. female (aOR: 2.413, CI 1.358-4.288, P=0.003); DM (aOR: 2.07, CI: 1.081-3.964, P=0.028); HTN (aOR 2.586, CI: 1.104-6.06, P=0.029). However, the odds ratio for BMI at 12 months was insignificant (aOR: 0.999, CI 0.948-1.053, P=0.98). Conclusion: At one year post transplantation, about two thirds of our renal transplant recipients required no or only one BP medication. Those who required more medications were more likely to be older, males, diabetic, or previously hypertensive. Recipients with abnormal baseline pre-transplant cardiovascular imaging were also more likely to require more medications. Reference:1. Taler SJ, Agarwal R, Bakris GL, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013;62.

236.8: Early Surgical Complications in Everolimus (EVR) Treated Renal Transplant Recipients

Introduction: De novo use of low dose Everolimus in combination with reduced-exposure of Tacrolimus (EVR+rTAC) is still limited by lack of evidences from long term follow-up data and by the wound healing issues reported in the early clinical experiences. For these reasons the combination of tacrolimus and mycophenolatemofetil (TAC+MMF) is more frequently adopted as immunosuppressive treatment in renal transplantation. Aim of this study was to analyze clinical safety and efficacy of once a day combination of EVR+rTAC vs standard TAC+MMF in de novo Renal Transplant Recipients (RTR). Methodology: We are reporting our preliminary data of a prospective clinical study in RTR who completed their first 5 years follow-up after renal transplantation. After randomization RTR received once a day low dose EVR (blood levels: 3 - 5 ng/ml) plus TAC (blood levels: 3 – 5 ng/ml) or standard TAC plus once a day mycophenolate mofetil (MMF+TAC) immunosuppression. Results: One hundred two renal transplant recipients entered the study and completed the 5 years follow-up. No significant differences were found between the two recipients groups EVR+rTAC (51 pts) and MMF+TAC (51 pts) in the demographic data: age, sex, BMI, time on dialysis, transplant waiting time, native renal disease, pre-transplant diabetes, ischemic heart disease. All patients received as induction low fixed dose of Thymoglobuline (50mg IV x 4 days: pre-op and on day1, 2, 3). The incidence of acute rejection was not significantly different between the two groups (EVR+rTAC: Rey 7.2% vs MMF+TAC Rey 9.4%). One year estimated GFR also was not significantly different: EVR+rTAC: eGFR 50 ml/min vs MMF+TAC: eGFR 51 ml/min). Early surgical complications (within 30 days post-op) were also not significantly different in the two groups: EVR+rTAC: 20% vs MMF+TAC: 17%. The analysis of the severity of these surgical complications according with the Clavien-Dindo classification, also found no significant differences in the grade of complications: EVR+rTAC:class1 #5, class 2 #1, class 3 #4 vs MMF+TAC: class1 #4, class 2 #0, class 3 #5. Finally, we adopted the preemptive strategy to prevent CMV infection in our RTR, by monitoring PCR-CMV-DNA without pre-emptive pharmacologic antiviral prophylaxis, in both the study groups. Our data indicate that pre-emptive CMV prophylaxis with PCR-CMV-DNA monitoring in the presence of the combination of EVE+TAC is very effective in the diagnosis of CMV reactivation up to month 6 after transplantation: EVR+rTAC, PCR-CMV-DNA positive 36% vs MMF+TAC: PCR-CMV-DNA positive 65%, p 0.003. This preemptive strategy, showing the significant inhibition of CMV replication by the mTOR inhibitor Everolimus is effective in RTR, cheaper respect to antiviral drugs and avoiding emergent CMV resistance. Conclusion: In conclusion, the immunosuppressive combination of low dose Everolimus and low dose Tacrolimus allows the same excellent clinical results of standard Tacrolimus and MMF therapy, without increasing early surgical complications, with the significant advantages of less CMV infections.

Comparison of Outcomes of Live and Deceased Donor Renal Transplantation-A Retrospective Study from a single center in South India

Background: Renal transplantation is the treatment modality of choice for patients with end-stage renal disease(ESRD). Living donors constitute the majority of the organ donor pool in India. Deceased donation program is only slowly evolving in the country. In this study, we aimed at comparing the outcome of live and deceased donor renal transplantation at our institute. Methods: This is a single-center, retrospective, observational study of renal transplant recipients from January 2010 to April 2016 conducted in a tertiary care centre in South India. The clinical profile, graft dysfunction, graft survival and patient survival rates of renal transplant recipients were analyzed. Results: Of 210 recipients, live donor renal transplant (LDRT) recipients were 176(83.80%) and deceased donor renal transplants (DDRT) were 34(16.19%). Delayed graft function was common in DDRT (64.7%) compared to LDRT (3.40%). Graft dysfunction episodes were commoner in DDRT (1.04 episodes/patient/year) compared to LDRT (0.43 episodes/patient/year). Higher rejection rate was seen in LDRT (25.56%) compared to DDRT (8.82%) with mean duration of follow up of 3.37± 1.80 years and 2.14 ± 1.12 years respectively. Modification of immunosuppression and noncompliance were the risk factors for rejection. Death censored graft survival rates at 6 months, 1 year and 5 years in LDRT were 98.9%, 97.2%, and 92.6% respectively and at 6 months, 1 year and 3.26 years in DDRT were 100%, 97%, and 94% respectively. Patient survival rates at 6 months, 1 and 5 years in LDRT were 94.3%, 91.5% and 86.4% respectively, and in DDRT patient survival rates at 6 months, 1 and 3.26 years were 91.2% 85.3% and 79.4% respectively. Though the patient survival rate was better in LDRT compared to DDRT, it did not reach statistical significance. Overall mortality rate was 14% and infection was the commonest (77.74%) cause of mortality. Mortality rates in LDRT and DDRT were 13.63% and 20.58% respectively. Conclusions: Live donors constitute the majority of the organ donor pool. DGF is commonly seen in DDRT. Rejection rate was higher in LDRT, with noncompliance and modification of immunosuppression being the risk factors. There is no difference in the patient and graft survival between LDRT and DDRT.

Quality of Life among Renal Transplant Recipients in Bahrain: A Single-Center Experience.

Although a positive effect of renal transplantation on quality of life (QOL) scores was demonstrated in numerous international studies, there are a few studies in renal transplant recipients in Arabic countries. The purpose of this study was to assess the QOL in renal transplant recipients in Bahrain. We used the standard QOL Index (QOLI) score instrument in Arabic languages. This study included 58 patients, aged 26-71 years, and 63.8% of them were males. We excluded patients below 18 years old and failed renal transplant at the time of the study. The highest QOL score was in the psychological/spiritual domain (87.4 ± 12.2), followed by the family domain (85.5 ± 13.1), the health and functioning domain (82.7 ± 13.3), and the social and economic domain (80.5 ± 13.9). There was a highly significant high positive correlation between the QOLI and each of the tested domains (P <0.001). Married participants had a significantly higher QOL score in the family domain, compared to unmarried participants (P = 0.025). The QOL scores in the health and functioning domain were significantly affected by the patient's social status, residence, and coexisting diabetes mellitus. In addition, the QOLI scores were significantly greater among patients who did their transplants in Bahrain (P = 0.045). Most of the renal transplant patients in Bahrain are satisfied with their QOL. Their QOL was also variably impacted by the different sociodemographic and clinical factors.

SUCCESSFUL CALCINEURIN-INHIBITOR-FREE IMMUNOSUPPRESSION REGIMEN WITH SIROLIMUS AND PREDNISONE IN LUNG TRANSPLANT RECIPIENTS: A CASE SERIES

SESSION TITLE: Fellows Transplantation Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: The current standard of care for immunosuppression after lung transplantation is the use of triple agents with a calcineurin inhibitor (CNI), cell cycle inhibitor (CCI), and corticosteroids (CS) with the calcineurin inhibitor (CNI) being the backbone of the regimen. However, the use of immunosuppressant drugs is frequently complicated by the development of malignancy, nephrotoxicity, cytopenias, and infection, usually requiring a reduction in immunosuppression. In cases where both CCIs and CNIs must be stopped, mTOR inhibitors are frequently used in an effort to maintain sufficient immunosuppression. A definitive role for mTOR inhibitors for immunosuppression post-lung transplant, however, remains unclear although there have been some studies in renal transplant recipients. There are challenges with transitioning to mTOR inhibitors due to concerns over wound healing in the first year, potential pulmonary toxicities, as well as the lack of data on efficacy. To our knowledge, there is no data on the outcomes of lung transplant patients maintained on dual immunosuppression with mTOR inhibitors and steroids alone. CASE PRESENTATION: We present a series of three lung transplant patients maintained on an immunosuppressant regimen of sirolimus and prednisone. All three patients remained free of acute cellular rejection and antibody-mediated rejection. Of the three patients, two remain alive and one patient died from multi-system organ failure secondary to sepsis. DISCUSSION: This small case series highlights the successful use of dual immunosuppression with mTOR inhibitors and corticosteroids in patients with contraindications to both calcineurin inhibitors and cell cycle inhibitors. CONCLUSIONS: More data is required to determine how mTOR-CS dual immunosuppression compares to traditional CCI-CNI-CS triple immunosuppression in regards to transplant rejection and the safest way to transition to this regimen when necessary. Reference #1: Ivulich S, Westall G, Dooley M, Snell G. The Evolution of Lung Transplant Immunosuppression. Drugs. 2018;78(10):965-982. doi:10.1007/s40265-018-0930-6 DISCLOSURES: No relevant relationships by Shambhu Aryal, source=Web Response No relevant relationships by Adam Cochrane, source=Web Response No relevant relationships by Margaret Fregoso, source=Web Response No relevant relationships by Vikramjit Khangoora, source=Web Response Consultant relationship with Veracyte Please note: $1001 - $5000 Added 04/03/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with United Therapeutics Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria

An Analysis of Epidemiology, Etiology, and Outcomes of Acute Pancreatitis in Renal Transplant Recipients

Background and objectivesAcute pancreatitis after renal transplantation is seldom seen yet a dreadful complication. The causes include traditional causes and immunosuppressive medications and viral infections. Classical symptoms are not always present at onset, causing delay in diagnosis. The available literature on pancreatitis in renal transplants is either as case reports or case series. Large studies with longer follow-up periods and outcome in renal transplant patients with pancreatitis are lacking. We conducted this retrospective study to analyze the incidence, clinical features, and causes of pancreatitis in our institute in post-azathioprine era. DesignWe conducted a single center retrospective study of renal transplant recipients who suffered at least 1 episode of acute pancreatitis during a period from January 2002 to September 2018. We followed International Association of Pancreatology/American Pancreatic Association evidence-based guidelines for confirming diagnosis of acute pancreatitis and included only patients who fulfilled these criteria. Once the diagnosis is confirmed we retrospectively analyzed the etiology, clinical features, management and outcomes of renal transplant recipients with pancreatitis. ResultsTwenty-six patients (men 81%; mean age 38.5 years) were included. Etiology included gallstones (19.3%), structural lesions (11.5%), viral infections (7.8%), and drugs. Clinical presentations, laboratory parameters were like pancreatitis in non-transplant patients. Graft dysfunction was noted in 20 patients (77%) and all showed either partial or complete recovery. Patient survival was high with 88% of the patients surviving the episode. ConclusionPancreatitis after renal transplantation is a rare complication with outcomes better than what has been reported in the past.

Changes in the commercial brand of tacrolimus lead to subtherapeutic trough levels and acute rejection in renal transplant recipients.

The vigilance of tacrolimus (TAC) trough levels is an essential part of renal transplant follow up. Reduced TAC trough levels and high variabilityare related to adverse outcomes.The aim of this study was to evaluate the impact of brand changes on tacrolimus (TAC) subtherapeutic (SubT) trough levels, acute rejection (AR), and kidney function. This is a prospective, observational cohort study of renal transplant recipients, between January 2016 and October 2018. Tacrolimus trough levels and brand used by the patientwere both registered at every consult. Tacrolimus values ≤3.5ng/mL were considered SubT. 445 patients were included. The median number of TAC brand changes was 2 (IQR, 1-4). Patients were grouped according to the number of brand changes: Group 1=0 (n=107), Group 2=1-4 (n=236), and Group 3=≥5 (n=102). Patients with the greatest number of brand changes had a greater proportion and number of SubT TAC trough levels (Group 1=36.4%, average 0.53; Group 2=39.8%, average 0.65, Group 3=59.8%, average 1.17, P<.001) and AR (Group 1=0.9%, Group 2=11%, Group 3=14.7%, P<.001). On multivariate analysis, SubT levels and the number of brand changes were related to AR. In Mexico, changes in TAC brand are associated with an elevated frequency of SubT levels. Brand changes and SubT levels are independently associated with acute rejection. The supply policies on TAC brands in Mexico require revision to avoid changing brands as much as possible.

A Prospective, Observational Study of Conversion From Immediate- to Prolonged-Release Tacrolimus in Renal Transplant Recipients in France: The OPALE Study.

BackgroundPotential benefits of once-daily, prolonged-release tacrolimus over the immediate-release formulation include improved adherence to immunosuppressives post transplantation. An observational study was performed to characterize real-world practice surrounding conversion from immediate- to prolonged-release tacrolimus in kidney transplant recipients.Material/MethodsWe performed a prospective, observational study of renal transplant recipients converted from immediate- to prolonged-release tacrolimus capsules. Conversion took place at the baseline visit, within the first 6 months of transplantation (early conversion group) or between 6 and 12 months of transplantation (late conversion group). Data collection was performed at routine follow-up at 6 and 12 months. Endpoints included conversion ratio from immediate- to prolonged-release tacrolimus, reasons for conversion, additional visits due to conversion, safety, and tolerability.ResultsThe analysis population comprised 591 patients. Baseline characteristics were similar between the 2 groups. The mean conversion ratio of the daily dose of tacrolimus was 0.98±0.17 in the early group and 0.99±0.09 in the late group. Time from conversion (mean ±SD) to first measurement of trough tacrolimus blood concentration was 12.1±11.6 and 27.6±26.7 days in the early and late groups, respectively. The highest number of additional visits required was 6 in the early conversion group, in 3 patients (0.7%), and 3 in the late conversion group, in 2 patients (1.6%). Conversion from immediate- to prolonged-release tacrolimus was associated with a very low rate of graft rejection.ConclusionsFavorable clinical outcomes and safety profiles were observed with conversion from immediate- to prolonged-release tacrolimus over 1 year following renal transplantation, with no marked differences between the early and late conversion groups.

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients.

Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients. CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations. The assay range was 0.9-30 mg/L with accuracy within 91%-99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 4°C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations. We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.

1505. Predictive Value of Early Post-Transplant Bacteriuria on Rates of Recurrent Urinary Tract Infections in the First Year After Renal Transplantation

BackgroundUrinary tract infection (UTI) is a common post-kidney transplant complication that has been associated with risk for allograft dysfunction. However, prior studies assessing risk factors for recurrent post-transplant UTI (rUTI) did not distinguish between asymptomatic bacteriuria and UTI. We hypothesize that early asymptomatic bacteriuria (EAB) and UTI after renal transplant are risk factors for rUTI.MethodsA single-center retrospective cohort study of renal transplant recipients at a tertiary care, academic medical center from May 1, 2010 to January 31, 2015. Data on epidemiology, comorbidities, donor cultures, number of UTIs, days of foley catheter use, and antibiotic therapy were obtained from the electronic medical record and transplant patient database. Inclusion criteria: >18 years old post kidney transplant during the study period. Exclusion criteria: rUTI prior to transplant or anatomical abnormality of native kidney(s). Definitions: Early post-transplant (EPT): <28 days after transplant. Positive culture: growth of >105 cfu/mL. UTI-(fever, dysuria, +/− allograft or suprapubic pain) + positive culture. EAB-asymptomatic bacteriuria in the EPT period. rUTI: ≥ 3 UTIs in 1 year or 2 UTIs in 6 consecutive months within the year post-transplant. UTI episodes were considered separate if occurred >3 weeks after completion of prior antibiotics. Data were analyzed by Fischer’s exact test and chi-square test.ResultsA total of 369 patients were included; 40.4% had EAB and 6% had a UTI in the EPT (eUTI). rUTI occurred in 5.7% of patients (n = 21). In the rUTI group, 8 (38.1%) had EAB, 8 (38.1%) had eUTI, and 5 (23.8%) had neither (P = 0.067). rUTI developed in 5.3% (8/149) of the EAB group vs. 36.4% (8/22) of the eUTI group (P < 0.005). No other variables were associated with rUTI. Total UTI episodes was greater with eUTI than EAB (mean 2.09 vs. 0.28, 95% CI 2.2–1.4, P < 0.005).ConclusionOnly eUTI increased the risk for rUTI. Although screening for bacteriuria is a common practice post-transplant, our data indicates that aggressive symptom screening would better predict likelihood of rUTI and in turn graft dysfunction. Future studies should address the potential benefit of prolonged prophylactic trimethoprim/sufamethoxazole in preventing rUTI.Disclosures All authors: No reported disclosures.

ANRIL as a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study.

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients. Several single-nucleotide polymorphisms (SNPs) in the ANRIL gene pathway have been associated with cardiovascular events (CE). The main objective was to ascertain whether ANRIL (rs10757278) and CARD8 (rs2043211) SNPs could mediate susceptibility to CE. This was an observational follow-up cohort study of renal transplant recipients at Bellvitge University Hospital (Barcelona) from 2000 to 2014. A total of 505 recipients were followed up until achievement of a CE. Patients who did not achieve the endpoint were followed up until graft loss, lost to follow-up or death. Survival analysis was used to ascertain association between genetic markers, clinical data, and outcome. Fifty-three patients suffered a CE after renal transplantation. Results showed a significant association between ANRIL SNP and CE. Homozygous GG for the risk allele showed higher risk for CE than A carriers for the protective allele [HR = 2.93(1.69-5.11), P < 0.0001]. This effect was maintained when it was analyzed in combination with CARD8, suggesting that CARD8 SNP could play a role in the ANRIL mechanism. However, our study does not clarify the molecular mechanism for the CARD8 SNP regulation by ANRIL. ANRIL SNP may predispose to the development of CE after successful kidney transplantation.

Skin disorders in renal transplant recipients: a retrospective study.

BackgroundImmunosuppressive therapy, which is necessary to avoid graft rejection in renal transplant recipients, presents an increased risk of several pathologies, namely infectious and neoplastic.ObjectivesTo identify the most frequent skin diseases and their clinical and demographical risk factors within a population of renal transplant recipients.MethodsA retrospective study of renal transplant recipients referred to dermatology visit and observed for the first time from January 2008 to December 2014.ResultsThe study included 197 patients, 120 men (60,9%). Mean age was 50,7 years (±13,4). 12 patients (6,1%) had previous skin cancer. Infections were the most frequent reason of referral (93/197; 44%). From the total referred, 18,3% (36/197) presented pre-cancerous lesions. Malignancy was diagnosed in 36 patients (18,3%), with 29 non-melanoma skin cancers (14,7%) and 7 Kaposi sarcomas (3,6%). Ratio of basal cell carcinoma to squamous cell carcinoma was 1,1:1. Non-melanoma skin cancer was significantly associated with older age (p = 0,002), male gender (p = 0,028), history of previous skin cancer (p = 0,002) and higher duration of immunosuppressive therapy (p<0,001).Study limitationsRetrospective study, with data from the first visit in dermatology. We didn't made classification on skin-types.ConclusionsThe great incidence of cutaneous infections and skin cancer is responsible for a significant morbidity. It is important to assure the regular dermatological follow-up of renal transplant recipients, which will promote the prevention, an early diagnosis and an efficient treatment.

A delicate balance between rejection and BK polyomavirus associated nephropathy; A retrospective cohort study in renal transplant recipients.

BackgroundThe immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN).In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied.Methods358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included.ResultsIncidence of BKPyV-viremia was not significantly different between the CsAM (n = 42/191) (22.0%) and the TacM (n = 36/167) (21.6%) group. Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03). Longitudinal data analysis showed a significant earlier decline of viral load in plasma in the CsAM group compared to the TacM group (p = 0.005).The incidence of biopsy proven acute rejection (BPAR) was significantly higher in the CsAM (19.9%) compared to the TacM (10.8%) (p = 0.02) group. Graft loss, estimated glomerular filtration rate and mortality rate did not differ in both treatment groups.ConclusionIn conclusion, this study shows that immunosuppressive treatment with Tac and MPA compared to CsA and MPA is associated with a lower incidence of BPAR, but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant.

Can the Double-J Ureteric Stent be Dispensed? A Prospective Randomized Study in Renal Transplant Recipients

Can the Double-J Ureteric Stent be Dispensed? A Prospective Randomized Study in Renal Transplant Recipients

Incidence of cardiovascular events and associated risk factors in kidney transplant patients: a competing risks survival analysis

BackgroundThe high prevalence of cardiovascular risk factors among the renal transplant population accounts for increased mortality. The aim of this study is to determine the incidence of cardiovascular events and factors associated with cardiovascular events in these patients.MethodsAn observational ambispective follow-up study of renal transplant recipients (n = 2029) in the health district of A Coruña (Spain) during the period 1981–2011 was completed. Competing risk survival analysis methods were applied to estimate the cumulative incidence of developing cardiovascular events over time and to identify which characteristics were associated with the risk of these events.Post-transplant cardiovascular events are defined as the presence of myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances, peripheral vascular disease and cardiovascular disease and death. The cause of death was identified through the medical history and death certificate using ICD9 (390–459, except: 427.5, 435, 446, 459.0).ResultsThe mean age of patients at the time of transplantation was 47.0 ± 14.2 years; 62% were male. 16.5% had suffered some cardiovascular disease prior to transplantation and 9.7% had suffered a cardiovascular event. The mean follow-up period for the patients with cardiovascular event was 3.5 ± 4.3 years. Applying competing risk methodology, it was observed that the accumulated incidence of the event was 5.0% one year after transplantation, 8.1% after five years, and 11.9% after ten years. After applying multivariate models, the variables with an independent effect for predicting cardiovascular events are: male sex, age of recipient, previous cardiovascular disorders, pre-transplant smoking and post-transplant diabetes.ConclusionsThis study makes it possible to determine in kidney transplant patients, taking into account competitive events, the incidence of post-transplant cardiovascular events and the risk factors of these events. Modifiable risk factors are identified, owing to which, changes in said factors would have a bearing of the incidence of events.

A Prospective Study of Renal Transplant Recipients: A Fall in Insulin Secretion Underpins Dysglycemia After Renal Transplantation.

BackgroundDysglycemia (encompassing impaired glucose tolerance and diabetes mellitus) arising after renal transplantation is common and confers a significant cardiovascular mortality risk. Nonetheless, the pathophysiology of posttransplant dysglycemia is not well described. The aim of this study was to prospectively and comprehensively assess glucose handling in renal transplant recipients from before to 12 months after transplantation to determine the underpinning pathophysiology.Materials and MethodsIntravenous and oral glucose tolerance testing was conducted before and at 3 and 12 months posttransplantation. An intravenous glucose tolerance test was also performed on day 7 posttransplantation. We followed up 16 transplant recipients for 3 months and 14 recipients for 12 months. Insulin secretion, resistance and a disposition index (DI (IV)), a measure of β cell responsiveness in the context of prevailing insulin resistance, were also determined.ResultsAt 12 months, 50% of renal transplant recipients had dysglycemia. Dysglycemia was associated with a dramatic fall in DI (IV) and this loss in β cell function was evident as early as 3 months posttransplantation (23.5 pretransplant; 6.4 at 3 months and 12.2 at 12 months posttransplant). Differences in the β cell response to oral glucose challenge were evident pretransplant in those destined to develop dysglycemia posttransplant (2-hour blood glucose level 5.6 mmol/L versus 6.8 mmol/L; P < 0.01).ConclusionsDysglycemia after renal transplantation is common, and the loss of insulin secretion is a major contributor. Subclinical differences in glucose handling are evident pretransplant in those destined to develop dysglycemia potentially heralding a susceptible β cell which under the stressors associated with transplantation fails.