One-year Post-transplantation Research Articles

Kidney Transplantation and Cellular Immunity Dynamics: Immune Cell Alterations and Association with Clinical and Laboratory Parameters.

Background/Objectives: The purpose of this study was to evaluate numerical changes in immune cells after successful kidney transplantation and associate their recovery with clinical and laboratory factors. Methods: In 112 kidney transplant recipients, we performed flow cytometry to evaluate counts of CD4+, CD8+, and regulatory T cells (Tregs), as well as natural killer (NK) cells, before kidney transplantation (T0) and three (T3), six (T6), and twelve (T12) months later. The results were associated with the recipient's age, cold ischemia time (CIT), the type of donor, dialysis method and vintage, and graft function in one year. Results: Total and CD8+ T cell counts increased gradually one year post transplantation in comparison with pre-transplantation levels, whereas the number of CD4+ T cells and Tregs increased, and the number of NK cells decreased in the first three months and remained stable thereafter. The recipient's age was negatively correlated with total, CD4+, and Treg counts at T12, whereas CIT affected only total and CD4+ T cell count. Moreover, recipients receiving kidneys from living donors presented better recovery of all T cell subsets at T12 in comparison with recipients receiving kidneys from cadaveric donors. Patients on peritoneal dialysis had increased numbers of total and CD8+ T cells, as well as NK cells. Finally, estimated glomerular filtration rate was positively correlated with Treg level and potentially CD4+ T cells one-year post transplantation. Conclusions: Successful kidney transplantation results in the recovery of most T cell subsets. Lower recipient age and better graft function contribute to increased T cell counts, whereas donor type and dialysis modality are the most important modifiable factors for optimal immune recovery.

#2132 Recipient outcomes after laparoscopic versus open living donor nephrectomy: a propensity score-matched cohort study

Abstract Background and Aims Kidney transplantation is the optimal treatment for end-stage renal disease. To meet the growing demand for kidney allografts and to ensure the well-being of donors, laparoscopic nephrectomy has been adopted leading to superior donor outcomes. However, data on recipient outcomes of laparoscopically retrieved grafts are underreported. The aim of the study is to estimate the impact of laparoscopic compared to open living donor nephrectomy (LDN, ODN) on recipient outcomes in the first-year post-transplant. Method This was an observational cohort study of primary data on 396 recipients who had undergone living kidney transplantation from January 2011 to December 2021 at the Clinic of Nephrology and Renal Transplantation of ‘Laiko’ hospital. Since October 2018 laparoscopic surgery has supplanted ODN in the reporting center. Graft function, the risk of adverse events, patient and graft survival within the first-year post-transplantation, were evaluated. A propensity score analysis was applied (2:1 nearest-neighbor matching, with a caliper width of 0.05). As a robustness check, the analysis was rerun on the sub-groups of low and high immunological risk patients. Results After propensity score matching, 389 patients were analyzed. One-year post-transplantation, renal function (−0.074 mg/dl, p: 0.063) patient (99.44% vs 100%, p: 0.27) and graft (99.43% vs 100%, p: 0.13) survival were statistically equal among LDN and ODN recipients. Laparoscopically retrieved grafts demonstrated statistically higher risk of delayed graft function (10.1%, p: 0.032) and higher risk for transfusion (12.9%, p:0.022). The risk for acute rejection, surgical complications and infections (Fig. 1), as well as the length of hospital stay did not differ between the two groups. Kidney function at one year was similar in LDN and ODN patients, regardless of the immunological risk. Low immunological risk patients demonstrated comparable risk of adverse events in the first post-transplant year. High-immunological risk patients after LDN after LDN exhibited greater risk for reoperation (16%, p: 0.0078) urologic complications (19.6%, p: 0.042) and bacterial infections (7.1%, p: 0.027) compared to ODN recipients during the first year after transplantation. Conclusion The results indicate that one-year post-transplantation, renal function, patient and graft survival are equivalent among recipients of allografts procured either laparoscopically or by open surgery, with similar risk of adverse events.

#650 Predictive value of LKDPI on recipient's renal function one year after kidney transplantation: single-centre experience

Abstract Background and Aims The selection of the appropriate living kidney donor can be challenging, given the absence of a definitive method to determine the quality of the renal graft. This decision requires a delicate balance, weighing the recipient's benefits while prioritizing the safety of the donor. Recently, a tool known as the Living Kidney Donor Profile Index (LKDPI) was proposed to assess living donor kidneys, based on various donor characteristics, so as to predict the probability of recipient's graft loss; however, the validation of its effectiveness still needs to be proven. Method We evaluated retrospectively 147 stable living kidney donors, who donated between 01/2021 and 11/2023 and are currently attending the Living Donor Clinic of our Department. Our study aimed to assess the impact of the LKDPI on the recipient's estimated renal glomerular filtration rate (eGFR) (measured by the CKD-EPI) one-year posttransplant. Additionally, dialysis vintage, cause of CKD, comorbidities and medication were also determined in all recipients. Results The study comprised 147 stable kidney recipients (KTR), each with their respective living donor. Of these, 96 (65.3%) were males, with a mean age 44.02 ± 13.96 years and a mean dialysis vintage of 1.8 ± 2.3 years. In parallel, living kidney donors were predominantly females (70.7%), with a mean age of 59.08 ± 10.36 years and a mean eGFR prior to donation of 95 ± 13.11 ml/min/1.73 m². Furthermore, 20.1% of kidney transplantations were ABO incompatible and the mean LKDPI score was 34.6 ± 25.9%. Data analysis revealed a statistically significant negative correlation between LKDPI and the recipient's GFR one year after transplantation (p < 0.0001), suggesting that higher LKDPI scores were associated with lower renal function in recipients. In a post hoc analysis, KTRs who were on CKD stage 1, one-year post-transplantation, demonstrated no statistical difference in LKDPI values, compared to stage 2 (p = 0.35). Meanwhile recipients on stage 3 exhibited comparable LKDPI values to those on stage 4 (p = 0.821). The main statistical discrepancy was particularly evident between CKD stage 2 and 3, as recipients with a LKDPI surpassing 25.6, experienced a transition from stage 2 to stage 3 within the first year following transplantation (p < 0.0001). In addition, after multivariate analysis there were no correlations between KTR's eGFR and age difference between donor and recipient or recipient's smoking history or medication. Last, dialysis vintage or the number of previous transplantations did not affect recipient's kidney function. Conclusion LKDPI seems to be a promising tool for predicting the outcome of kidney transplantation, concerning the renal function of KTR particularly at the end of the first-year post-transplant However, it needs to be thoroughly evaluated before being considered as a decision-making factor in living kidney transplantations.

#623 One-year outcome of kidney transplant recipients harbouring complement regulatory gene mutation

Abstract Background and Aims Thrombotic Microangiopathy (TMA) is associated with genetic abnormalities in complement regulatory pathways. The impact of complement regulatory gene (CRG) mutation on post-transplant TMA in Indian kidney transplant recipients (KTR) is unknown. This study was conducted to ascertain an association between post-transplant renal limited TMA and the risk of graft failure in KTRs harbouring mutations in genes encoding complement-regulatory proteins. Method A Single Centre, Prospective Cohort Study was undertaken to assess the incidence of post-transplant renal limited TMA in KTRs with mutations in genes encoding complement regulatory proteins. Patients enrolled over one year were followed up for one-year post-transplantation. Genetic testing was performed with MLPA and Clinical exome sequencing. Results 138 KTRs with a mean age of 36.39 ± 12.39 years were enrolled. CRG mutation was seen in 96/138 (69.6%) KTRs. Duplication of the CFHR gene (n = 72) was most prevalent followed by mutations in CFH (n = 6), CFI (n = 2), MCP (n = 2), and DGKE (n = 1). Mutations in CFB, C3, and THBD genes were not detected. The Incidence of Post transplant renal limited TMA in KTRs with CRG mutations is 9.37% (9/96). Mutation related to aHUS was seen in 9 out of 11 patients who developed TMA. There was no significant difference in eGFR of patients with or without CRG mutation at the end of 1 year. Conclusion The prevalence of CRG mutation in KTRs is high and the majority of patients with post-transplant de novo TMA had CRG mutations. The graft functions at the end of 1 year were similar in patients with or without CRG gene mutation. This study suggests that the presence of CRG mutation should not preclude the option of Kidney transplantation in a patient with ESRD.

Experience with Epstein barr virus and Cytomegalovirus infection in pediatric liver transplant recipients: A 2014–2017 study

IntroductionThis study presents our experience with Epstein Barr virus (EBV) and Cytomegalovirus (CMV) infections in the pediatric liver transplant population and their potential association with the development of the post-transplant lymphoproliferative syndrome (PTLD). Patients and methodsThis retrospective descriptive study covers the period from 2014 to 2017 and includes pediatric liver transplanted recipients who underwent viral load monitoring for EVB and CMV during the first-year post-transplant. ResultsA total of 89 patients were included in the study, with a median age of 0.68 years (RIQ 0.31–0.96) (10.8 months RIQ 8.4–25.2). The most common underlying pathology leading to transplantation was biliary atresia, observed in 55 (61.6 %) cases. Regarding EBV viral loads, values exceeding 10,000 copies/ml were observed in 9 (8 %) patients at 3 months, 33 (29.3 %) at 6 months, 31 (27.6 %) at 9 months and 25 (22.3 %) at 12 months post-transplantation. The probability of developing EBV infection within one-year post-transplantation was 81.3 %, while the probability of CMV infection was 29 %. A total of 8 (8.9 %) biopsy-confirmed graft rejections occurred, only 1 was EBV and CMV-negative. The likelihood of graft rejection in patients with EBV infection was 21.5 %, and for CMV it was 20.8 %. Importantly, only one case of PTLD was documented during 12 months follow-up. ConclusionCharacterizing this pediatric liver transplant population and monitoring EBV and CMV viral loads enables timely interventions, potentially reducing the risk of PTLD and graft rejection.

Biochemical Clusters as Substitutes of Bone Biopsies in Kidney Transplant Patients.

Bone and mineral metabolism abnormalities are frequent in kidney transplant recipients and have been associated with cardiovascular morbidity. The primary aim of this study was to analyse the association between routine clinically available biochemical evaluation, non-routine histomorphometric bone evaluation, and vascular disease in kidney transplanted patients. A cross-sectional analysis was performed on 69 patients, 1-year after kidney transplantation. Laboratory analysis, radiography of hands and pelvis, bone biopsy, bone densitometry, and coronary CT were performed. One-year post-transplantation, nearly one-third of the patients presented with hypercalcemia, 16% had hypophosphatemia, 39.3% had iPTH levels > 150pg/mL, 20.3% had BALP levels > 40 U/L, and 26.1% had hypovitaminosis D. Evaluation of extraosseous calcifications revealed low Adragão and Agatston scores. We divided patients into three clusters, according to laboratory results routinely used in clinical practice: hypercalcemia and hyperparathyroidism (Cluster1); hypercalcemia and high BALP levels (Cluster2); hypophosphatemia and vitamin D deficiency (Cluster 3). Patients in clusters 1 and 2 had higher cortical porosity (p = 0.001) and osteoid measurements, although there was no difference in the presence of abnormal mineralization, or low volume. Patients in cluster 2 had a higher BFR/BS (half of the patients in cluster 2 had high bone turnover), and most patients in cluster 1 had low or normal bone turnover. Cluster 3 has no differences in volume, or turnover, but 60% of the patients presented with pre-osteomalacia. All three clusters were associated with high vascular calcifications scores. Vascular calcifications scores were not related to higher bone mineral density. Instead, an association was found between a higher Adragão score and the presence of osteoporosis at the femoral neck (p = 0.008). In conclusion, inferring bone TMV by daily clinical biochemical analysis can be misleading, and bone biopsy is important for assessing both bone turnover and mineralization after kidney transplantation, although hypophosphatemia combined with vitamin D deficiency is associated with abnormal mineralization. The presence of hypercalcemia with high levels of PTH or high levels of BALP, or hypophosphatemia and vitamin D deficiency should remind us to screen vascular calcification status of patients.Clinical Research: ClinicalTrials.gov ID NCT02751099.

Relation between global longitudinal strain and acute rejection in pediatric patients within the first-year post heart transplant

BackgroundAcute rejection leading to graft dysfunction remains a major cause of morbidity and mortality. In adults, assessment of global longitudinal strain (GLS) using speckle tracking echocardiography (STE) has been used as an early marker for graft dysfunction. Studies evaluating GLS in a sizable pediatric transplant population are scarce. ObjectivesWe sought to determine association between GLS and acute rejection within first-year post-transplantation in pediatric patients. MethodsPatients 0 to 18 years old who received heart transplants (HT) at Cleveland Clinic Children's Hospital after April 2013 were identified. Clinical data was collected from pre-transplant evaluation and post-transplant surveillance endomyocardial biopsy (EMB) visit from time of transplantation to one-year post-transplantation. Left ventricular (LV) GLS was measured retrospectively using vendor independent software. Significant rejection was defined by escalation in immunosuppression therapy due to pathology or clinical diagnosis. Trends of GLS were compared between patients with (Group 1) and without (Group 2) rejection, controlled for age. At the visit of rejection diagnosis, GLS rejection measurements were compared to the range of “normal”, non-rejection measurements. ResultsTwenty-seven patients met inclusion criteria. Eight patients (29.6 %) had at least one clinically significant rejection episode. There was no significant difference in GLS at the first endomyocardial biopsy visit between groups. At last biopsy visit, subjects with rejection had significantly worse GLS (p ≤ 0.001). In a mixed effect model, average global, 3-chamber, and 4-chamber systolic strain had significant interaction of group and time (p = 0.016, 0.033, 0.003, respectively). Systolic strain in those views significantly worsened over time in rejection group while remaining stable in non-rejection group. GLS of subjects with rejection were worse and out of the range of “normal” by the time of the third EMB visit. ConclusionsThere was a trend toward worse GLS in those who developed acute rejection within first year post-transplant compared to those without rejection.

Discovery of Biomarkers Related to Interstitial Fibrosis and Tubular Atrophy among Kidney Transplant Recipients by mRNA-Sequencing.

Interstitial fibrosis and tubular atrophy (IF/TA) after kidney transplantation causes a chronic deterioration of graft function. IF/TA can be diagnosed by means of a graft biopsy, which is a necessity as non-invasive diagnostic methods are unavailable. In this study, we identified IF/TA-related differentially expressed genes (DEGs) through next-generation sequencing using peripheral blood mononuclear cells. Blood samples from kidney transplant recipients undergoing standard immunosuppressive therapy (tacrolimus/mycophenolate mofetil or mycophenolate sodium/steroid) and diagnosed as IF/TA (n = 41) or normal (controls; n = 41) at their one-year protocol biopsy were recruited between January of 2020 and August of 2020. DEGs were derived through mRNA sequencing and validated by means of a quantitative real-time polymerase chain reaction. We identified 34 DEGs related to IF/TA. ADAMTS2, PLIN5, CLDN9, and KCNJ15 demonstrated a log2(fold change) of >1.5 and an area under the receiver operating characteristic curve (AUC) value of >0.6, with ADAMTS2 showing the largest AUC value and expression levels, which were 3.5-fold higher in the IF/TA group relative to that observed in the control group. We identified and validated DEGs related to IF/TA progression at one-year post-transplantation. Specifically, we identified ADAMTS2 as a potential IF/TA biomarker.

Cyclophosphamide with cyclosporine A for graft-versus-host disease prophylaxis in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation from human leucocyte antigen-matched donors

BackgroundGraft-versus-host disease (GVHD) is one of the most severe complications in patients with acute myeloid leukemia (AML) who underwent allogenic hematopoietic stem cell transplantation (HSCT). This study addressed the effectiveness and safety outcomes of high dose post-transplant cyclophosphamide (PT-CY) followed by cyclosporine A (CSA) as a GVHD prophylaxis protocol. Patients and MethodsFrom January 2019 to March 2021, AML patients who underwent HSCT, and received high-dose PT-CY followed by CSA were prospectively recruited, assessed, and followed up for one-year post-transplantation (PT). The cumulative incidences of both acute GVHD (aGVHD) at 100 days PT, and chronic GVHD (cGVHD) at one-year PT were assessed. ResultsThis study included 52 patients. The cumulative incidence (95% CIs) of aGVHD was 2.3% (0.3 – 15.4%), while the cumulative incidence of cGVHD was 23.2% (12.2–41.5%). The cumulative incidence of relapse and non-relapse mortality were 15.6%, and 7.9%, respectively. The median duration to reach neutrophil and platelet engraftment was 17 and 13 days, respectively. The overall, progression-free, and GVHD-free/relapse-free survival rates (95% CIs) were 89.6% (76.6 – 95.6%), 77.7% (62.1–87.5%), and 58.2% (41.6 – 71.7%) respectively. The cumulative incidences of the main transplant-related complications were; neutropenic sepsis (48.3%), cytomegalovirus reactivation (21.7%), pneumonia (13.8%), hemorrhagic cystitis (17.8%), septic shock (4.9%), and CSA toxicity (48.9%). ConclusionPT-CY followed by CSA was associated with low cumulative incidences of both aGVHD and cGVHD without increase in either the relapse or transplant-related complications; so, considered as a promising protocol to be widely applied in the settings of HLA-matched donors.

2105. Early-onset and Late-onset BK Polyomavirus-associated Nephropathy: A 10-year Retrospective Analysis

Abstract Background Polyomavirus-associated nephropathy (BKVAN) is one of the serious causes of allograft dysfunction and allograft loss in kidney transplant (KT) patients. Most of the patients were diagnosed with BKVAN within the first year after transplantation but some more cases of BKVAN occur later. A study focused on the differentiation between early and late-onset BKVAN is needed. Methods We conducted a retrospective cohort study among KT recipients at Ramathibodi Hospital between January 2010 – December 2020. The incidence of early-onset (diagnosed within 1 year) and late-onset (diagnosed after 1 year) BKVAN, as well as composite kidney allograft outcomes, were compared. Results From 1032 KT recipients, 645 (62.5%) were screened for BK viral infection. BKVAN was diagnosed in 83 (12.8%) patients. Of those, 46 (55.4%) and 37 (44.6%) were diagnosed with early-onset and late-onset BKVAN, respectively. Composite kidney allograft outcomes of GFR decline≥ 40% from baseline, graft loss or death were greater in early-onset BKVAN compared to late-onset BKVAN (7.5 vs 5.52 per 1000 person-months; hazard ratio 0.47; 95%CI, 0.23-0.95; P=0.037). In multivariate analysis, female gender and living-related kidney transplantation (LRKT) were independently associated with late-onset BKVAN compared to early-onset BKVAN. The more advanced the BKVAN diagnosis, the worse the allograft outcome occurs, even with optimizing immunosuppressive drugs and adjunctive therapy. Conclusion BKVAN could occur later after one-year post-transplantation, although relatively better composite kidney outcomes were observed compared to early-onset BKVAN. Female individuals who underwent living-related KT should be considered for BK virus preemptive monitoring beyond one year to detect this late-onset BK virus infection. Disclosures All Authors: No reported disclosures.

Post-Transplantation Anemia and Risk of Death Following Lung Transplantation

Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated. We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models. A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P=0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P=0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07). Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.

242.8: The Impact of Dialysis Vintage on Cardiovascular Risk Factors And the Findings of Cardiovascular Screening Work Up of Renal Transplant Candidates

Methods: In a single center retrospective chart-review study, we reviewed the outcomes renal transplant recipients who underwent renal transplant from January 2017 to May 2020. We divided the group based on their dialysis vintage, less than 3 years versus more than 3 years. We collected the data about the patients’ demographics, cardiovascular risk factor, dialysis modality, pre-transplant work-up images, and the changes in cardiovascular risk factors in the first post-transplantation year. Results: We included 278 patients, 109 patients in the longer vintage group and 169 patients in the shorter vintage group. The mean age 43.8±16.1 and 164 patients (59%) were male. The mean dialysis vintage in the shorter group was 1± 0.1 year, and 5.7± 2.7 years in the longer vintage group, p <0.001. The most common comorbidities were hypertension (76%), followed by diabetes mellitus (41.7%), and were present in similar proportions of both groups. Compared to the shorter dialysis vintage group, those who had longer dialysis vintage were more likely to have a deceased kidney donor (36.7% vs 8.9%, p <0.001), receive hemodialysis (88.1% vs 76%; p=0.006), predominantly through an arteriovenous fistula (55% vs 20.7%; p <0.001). The results of pretransplant work up including cardiac stress test, calcium scoring, coronary angiogram, cardiac ejection fraction, left ventricular hypertrophy, wall motion abnormalities and the degree of calcifications of pelvic arteries on pelvic Ct scan did not differ between the two groups. In the first post-transplantation year, patients in the longer vintage group were more likely to have reduction in their systolic blood pressure (-7.1±20.7 mmHg vs -1.6±17.5; p=0.027) and were at a higher risk of developing persistent hyperparathyroidism, defined as parathyroid hormone (iPTH) greater than 25.5 pmol/l at one year post transplantation, (27% vs 18%, p=0.003). However, patients in the shorter vintage group were more likely to have post-transplant weight gain (6.8±8.8 kg vs 4.7±; p=0.039). Post transplantation diabetes (PTDM) and morbid obesity at one-year post-transplantation were similar between the two groups. Conclusions: Our study showed that patients with dialysis vintage up to 3 years were not different in their baseline traditional risk factors, cardiovascular pre-transplant work up, nor the changes post renal transplant. This suggest that the increase of mortality related to dialysis vintage might be related to other factors such as uremia, electrolytes shifts and/ or infections. Further studies with longer follow up are needed to investigate if dialysis vintage longer than three years would affect the pre-transplant cardiovascular risk factors or the findings of pre-transplant cardiovascular imagings.

P8.082: Incidence and Associated Factors With Uncontrolled Hypertension at 12- Months Post-renal Transplantation

Background: Uncontrolled hypertension (HTN) after renal transplantation is not uncommon. However, our center has not studied its incidence and risk factors post kidney transplantation before. Method: A single-center retrospective study of the renal transplant recipients who underwent kidney transplantation between January 2017 to May 2020 with12 months of follow-up. The goal target of hypertension treatment during this retrospective study was <140/90 mmHg as per the published guidelines at that time. We divided patients according to their blood pressure (BP) control at 12 months post kidney transplantation into two groups: controlled BP (≤140/90) and uncontrolled BP(> 140/90). We studied the association between the patients’ demographics and baseline cardiovascular risk factors and uncontrolled HTN 12 months post kidney transplantation. We also studied the association between pretransplant (baseline) cardiovascular imagings and uncontrolled HTN at 12 months. These tests included:(ejection fraction, wall motion abnormalities on echo, calcium scoring, perfusion stress test, cardiac angiogram, and the degree of calcifications on CT of pelvic arteries). Additionally, we studied the changes seen during the first 12 months post kidney transplantation. These included: creatinine change, rejection, weight change, A1C change, post-transplant diabetes, LDL change, PTH change from baseline, and persistent hyperthyroidism. Results: A total of 254 renal transplant recipients were included. 74% were ≥ 30 years, 58% were men, and 80% were living-donor kidney recipients. Preemptive transplantation was 10.1%, PD: 11.5% and HD: 78.4%. At one year, 76 (29.9%) of the patients did not attain the BP goal of 140/90. SBP decreased from baseline to 12 months by -7.2±18.6 mmHg in the group with controlled BP and whereas it increased by 3.5±16.9 mmHg in the group with uncontrolled BP. (P:<0.001). DBP decreased from baseline to 12 months by -4.1±12 mmHg in the group with controlled BP, whereas it increased by 2±13.7 mmHg in the group with uncontrolled BP (P<0.001). Among characteristics and baseline cardiovascular risk factors, factors associated with uncontrolled HTN included age (47 VS 41 years, P:0.008) and DM (P:0.012). Whereas gender, dialysis vintage, preemptive transplantation, type of dialysis (hemodialysis VS peritoneal dialysis), type of transplant (living donor kidney transplant VS deceased donor kidney transplant), and smoking were not different among the two groups. None of the pre-transplant (baseline) cardiovascular imaging findings were associated with having uncontrolled BP >140/90 at 12 months. Similarly, there was no association between uncontrolled HTN and creatinine change from baseline, rejection, weight change, A1C change, post-transplant diabetes, LDL change, PTH change from baseline, and persistent hyperthyroidism. However, higher BMI at 12 months was associated with a higher incidence of uncontrolled HTN (BMI 27.2±5.9 vs. 29.2±5.4, P: 0.013). Multivariate analysis showed that the predictors of uncontrolled blood pressure (>149/90 mmHg) included a higher creatinine (OR=1.016, CI=1.004-1.028. p=0.01) and smoking (OR=3.58, CI=1.001-12.8. p=0.05). Conclusion: At one-year post renal transplantation, about one-third (29.9%) of the renal transplant recipients had uncontrolled hypertension despite multiple BP medications. SBP and DBP significantly trended up from baseline after transplantation in those with uncontrolled hypertension. In contrast, SBP and DBP significantly decreased from baseline after transplantation in those with controlled hypertension. This interesting finding requires further confirmation by a controlled prospective study.

Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial

BackgroundType-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients.MethodsAfter receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation.ResultsThe results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices.ConclusionsTaken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes.Trial registration: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) (https://en.irct.ir/trial/23256) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). (https://clinicaltrials.gov/ct2/show/NCT04078308).

Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Organ Transplantation.

Organ transplantation is the most preferred treatment option for end-stage organ diseases; however, allograft rejection is the major hurdle in successful long-term transplant survival. In spite of developing better HLA matching and more effective immunosuppressive regimen, one-year graft survival has been increased by nearly 90% and the incidence of acute rejection by one-year post-transplantation has been decreased by 12.2% in the last decades, chronic allograft rejection has remained as one of the major obstacles to the long-lasting survival of the transplanted allograft. Therefore, seemingly preventing the allograft rejection and inducing immunological tolerance against transplanted allografts is one of the primary goals in transplantation research to enable long-lasting graft survival. Various mechanisms such as long noncoding RNAs (lncRNAs) have been proposed that induce immune tolerance by modulating the gene expression and regulating innate and adaptive immune responses during transplantation. Besides, because of involvement in regulating epigenetic, transcriptional, and post-translational mechanisms, lncRNAs could affect allograft status. Therefore, these molecules could be considered as the potential targets for prediction, prognosis, diagnosis, and treatment of graft rejection. It is suggested that the noninvasive predictive biomarkers hold promise to overcome the current limitations of conventional tissue biopsy in the diagnosis of rejection. Hence, this review aims to provide a comprehensive overview of lncRNAs and their function to facilitate diagnosis, prognosis, and prediction of the risk of graft rejection, and the suggestive therapeutic choices after transplantation.

Renal recipients\u2019 knowledge and self-efficacy during first year after implementing an evidence based educational intervention as routine care at the transplantation clinic

BackgroundFollowing an implementation plan based on dynamic dialogue between researchers and clinicians, this study implemented an evidence-based patient education program (tested in an RCT) into routine care at a clinical transplant center. The aim of this study was to investigate renal recipients’ knowledge and self-efficacy during first year the after the intervention was provided in an everyday life setting.MethodsThe study has a longitudinal design. The sample consisted of 196 renal recipients. Measurement points were 5 days (baseline), 2 months (T1), 6 months (T2), and one-year post transplantation (T3). Outcome measures were post-transplant knowledge, self-efficacy, and self-perceived general health.ResultsNo statistically significant changes were found from baseline to T1, T2, and T3. Participants’ levels of knowledge and self-efficacy were high prior to the education program and did not change throughout the first year post transplantation.ConclusionRenal recipients self-efficacy and insight in post-transplant aspects seem to be more robust when admitted to the hospital for transplantation compared to baseline observations in the RCT study. This may explain why the implemented educational intervention did not lead to the same positive increase in outcome measures as in the RCT. This study supports that replicating clinical interventions in real-life settings may provide different results compared to results from RCT’s. In order to gain a complete picture of the impacts of an implemented intervention, it is vital also to evaluate results after implementing findings from RCT-studies into everyday practice.

A high concentration of TGF-β correlates with opportunistic infection in liver and kidney transplantation

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients.Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB.Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations.TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.

POS-119 Factors That Influence Delayed Graft Function in Kidney Transplants: A Single-Center Paired Kidney Analysis

Delayed graft function (DGF) is an early complication of kidney transplant which imposes several clinical factors related to donor, recipient and organ transplantation procedures. The aim of our study is to evaluate the risk factors of delayed graft function (DGF) and its impact on renal transplantation. We conducted a retrospective study consisting of 86 subjects who underwent kidney transplantation from 2010 to 2019. DFG was defined as requirement for dialysis within the first week after transplantation. DGF occurred in 7 of the 86 (8.1%) kidney transplant-recipients divided into 5 men and 2 women with a mean age of 42.4 +- 11.3 years. The causal nephropathy was mainly glomerular in 3 patients. patients received grafts from deceased donor in 4 cases. the dialysis duration was >12 months in all cases. 6 patients received immunosuppressant induction treatment based on anti-thymocyte globulin (4 patients) and basiliximab (2 patients). Mean warm and cold ischemic time was respectively at 35,33+-17 minutes and 21+-5.7 hours. At one-year post transplantation, the survival graft and patient rate was at 85.7%. Risk factors idenditified for DFG were: recipient age (p=0,05), hypertensive history (p=0,024), body mass index of recipient (p=0,027), deceased donor (p=0,000), living-related kidney transplantation donors (p=0,002), anti thymocyte globulin for induction therapy (p= 0,006) Understanding risk factors of DFG will help into the management of kidney transplantation and improve the outcomes by reducing this factors as much as possible.

Myocardial structural and functional changes in patients with liver cirrhosis awaiting liver transplantation: a comprehensive cardiovascular magnetic resonance and echocardiographic study

BackgroundCardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation.MethodsThis study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19).ResultsCMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: − 24.2 ± 2.7% in cirrhosis vs − 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from − 24.9 ± 2.4% to − 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001).ConclusionsMyocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Profiles of B-cell subsets in immunologically stable renal allograft recipients and end-stage renal disease patients

BackgroundPost-transplantation pharmacotherapies typically employ combinations of immunosuppressive agents that have been designed for targeted inhibition of T-cells and T-cell subsets. Studies of acute and chronic effects of clinically employed immunosuppressive agents on B-cells and B-cell subsets are significantly fewer in number and warrant further investigation. Accordingly, the goal of the present cross-sectional study is to functionally evaluate differences of B-cell subsets in patients with end-stage renal disease (ESRD) and immunologically stable renal transplant patients. Patients and methodsOf 103 patients who underwent renal transplantation, 73 patients were immunologically stable without rejection or infection. Among them, 34 patients were one-year post-transplantation, and 39 patients were five-year post-transplantation. The study also included 35 ESRD patients and 36 healthy volunteers. Flow cytometry identified B-cell subsets in the study groups. ResultsRenal allograft recipients had reduced percentages of total B-cells (CD19+) and regulatory B-cells (Breg) (CD38highCD27 + CD24+) compared with healthy controls. The percentage of transitional B-cells (IgM + CD38highCD24high) and marginal zone (MZ) B-cells (IgD-CD27+) was reduced in transplant recipients compared with patients with ESRD and healthy volunteers. The highest percentage of plasma cells (PCs) (CD38highCD27 + CD24-) was in patients with ESRD. In five-year post-transplantation group, CD38lowCD21- B-cells increased when compared with the other groups. Healthy volunteers and patients with ESRD had fewer unswitched memory (UM) B-cells (IgM + IgD + CD38lowCD27+), and increased isotype switched memory (ISM) B-cells (IgM-IgD-CD38lowCD27+). There was no difference in the percentage of naïve B-cells (IgD + CD27-) among diverse groups. ConclusionsThe percentages of the total, transitional, Breg, PCs, MZ, and UM B-cell subsets in immunologically stable renal allograft recipients were significantly different from healthy controls. However, B-cell subsets in patients with ESRD were minimally different with immunologically stable renal allograft recipients.