Journal Of Transplantation[JOURNAL]
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200 papers
Intermediate-Term Outcomes of Dual Adult versus Single-Kidney Transplantation: Evolution of a Surgical Technique.
Islam AK, Knight RJ, Mayer WA … +8 more , Hollander AB, Patel S, Teeter LD, Graviss EA, Saharia A, Podder H, Asham EH, Gaber AO
J Transplant · 2016 · PMID 27478630 · Full text
Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compa...
Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.
Effectively Screening for Coronary Artery Disease in Patients Undergoing Orthotopic Liver Transplant Evaluation.
Lee BC, Li F, Hanje AJ … +3 more , Mumtaz K, Boudoulas KD, Lilly SM
J Transplant · 2016 · PMID 27418975 · Full text
Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this...
Coronary artery disease (CAD) is prevalent in patients with end-stage liver disease and associated with poor outcomes when undergoing orthotopic liver transplantation (OLT); however, noninvasive screening for CAD in this population is less sensitive. In an attempt to identify redundancy, we reviewed our experience among patients undergoing CAD screening as part of their OLT evaluation between May 2009 and February 2014. Demographic, clinical, and procedural characteristics were analyzed. Of the total number of screened patients (n = 132), initial screening was more common via stress testing (n = 100; 75.8%) than coronary angiography (n = 32; 24.2%). Most with initial stress testing underwent angiography (n = 52; 39.4%). Among those undergoing angiography, CAD was common (n = 31; 23.5%). Across the entire cohort the number of traditional risk factors was linearly associated with CAD, and those with two or more risk factors were found to have CAD by angiography 50% of the time (OR 1.92; CI 1.07-3.44, p = 0.026). Our data supports that CAD is prevalent among pre-OLT patients, especially among those with 2 or more risk factors. Moreover, we identified a lack of uniformity in practice and the need for evidence-based and standardized screening protocols.
Current Treatment Approaches to HCC with a Special Consideration to Transplantation.
Bhardwaj N, Perera MT, Silva MA
J Transplant · 2016 · PMID 27413539 · Full text
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients.
Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation.
El Moghazy W, Kashkoush S, Meeberg G … +1 more , Kneteman N
J Transplant · 2016 · PMID 27403337 · Full text
Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods...
Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC.
Liver Transplantation for Hepatocellular Carcinoma: A Single Center Resume Overlooking Four Decades of Experience.
Emmanouilidis N, Peters R, Ringe BP … +7 more , Güner Z, Ramackers W, Bektas H, Lehner F, Manns M, Klempnauer J, Schrem H
J Transplant · 2016 · PMID 27057348 · Full text
Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 19...
Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included. Predictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and χ (2)-tests where appropriate. Results. HCCR was the single strongest hazard for survival (exp(B) = 10.156). Hazards for HCCR were tumor staging beyond the histologic MILAN (exp(B) = 3.645), bilateral tumor spreading (exp(B) = 14.505), tumor grading beyond G2 (exp(B) = 8.668), and vascular infiltration of small or large vessels (exp(B) = 11.612, exp(B) = 18.324, resp.). Grading beyond G2 (exp(B) = 10.498) as well as small and large vascular infiltrations (exp(B) = 13.337, exp(B) = 16.737, resp.) was associated with higher hazard ratios for long-term survival as compared to liver transplantation beyond histological MILAN (exp(B) = 4.533). Tumor dedifferentiation significantly correlated with vascular infiltration (χ (2) p = 0.006) and intrahepatic tumor spreading (χ (2) p = 0.016). Conclusion. LT enables survival from HCC. HCC dedifferentiation is associated with vascular infiltration and intrahepatic tumor spreading and is a strong hazard for HCCR and survival. Pretransplant tumor staging should include grading by biopsy, because grading is a reliable and easily accessible predictor of HCCR and survival. Detection of dedifferentiation should speed up the allocation process.
Lung Transplantation in Patients with High Lung Allocation Scores in the US: Evidence for the Need to Evaluate Score Specific Outcomes.
Hayanga JA, Lira A, Vlahu T … +5 more , Yang J, Aboagye JK, Hayanga HK, Luketich JD, D'Cunha J
J Transplant · 2015 · PMID 26798504 · Full text
Objective. The lung allocation score (LAS) resulted in a lung transplantation (LT) selection process guided by clinical acuity. We sought to evaluate the relationship between LAS and outcomes. Methods. We analyzed Scient...
Objective. The lung allocation score (LAS) resulted in a lung transplantation (LT) selection process guided by clinical acuity. We sought to evaluate the relationship between LAS and outcomes. Methods. We analyzed Scientific Registry of Transplant Recipient (SRTR) data pertaining to recipients between 2005 and 2012. We stratified them into quartiles based on LAS and compared survival and predictors of mortality. Results. We identified 10,304 consecutive patients, comprising 2,576 in each LAS quartile (quartile 1 (26.3-35.5), quartile 2 (35.6-39.3), quartile 3 (39.4-48.6), and quartile 4 (48.7-95.7)). Survival after 30 days (96.9% versus 96.8% versus 96.0% versus 94.8%), 90 days (94.6% versus 93.7% versus 93.3% versus 90.9%), 1 year (87.2% versus 85.0% versus 84.8% versus 80.9%), and 5 years (55.4% versus 54.5% versus 52.5% versus 48.8%) was higher in the lower groups. There was a significantly higher 5-year mortality in the highest LAS group (HR 1.13, p = 0.030, HR 1.17, p = 0.01, and HR 1.17, p = 0.02) comparing quartiles 2, 3, and 4, respectively, to quartile 1. Conclusion. Overall, outcomes in recipients with higher LAS are worse than those in patients with lower LAS. These data should inform more individualized evidence-based discussion during pretransplant counseling.
Risk Factors Associated with Increased Morbidity in Living Liver Donation.
Candido HL, da Fonseca EA, Feier FH … +8 more , Pugliese R, Benavides MA, Silva ED, Gordon K, de Abreu MG, Canet J, Chapchap P, Neto JS
J Transplant · 2015 · PMID 26788361 · Full text
Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. Thi...
Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., p < 0.001). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p = 0.008), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p = 0.012), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p = 0.004) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors.
Plasma Exchange for the Recurrence of Primary Focal Segmental Glomerulosclerosis in Adult Renal Transplant Recipients: A Meta-Analysis.
Vlachopanos G, Georgalis A, Gakiopoulou H
J Transplant · 2015 · PMID 26697207 · Full text
Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria is not uncommon and has detrimental consequences on renal allograft survival. A putative circ...
Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria is not uncommon and has detrimental consequences on renal allograft survival. A putative circulating permeability factor has been implicated in the pathogenesis leading to widespread use of plasma exchange (PLEX). We reviewed published studies to assess the role of PLEX on treatment of rFSGS in adults. Methods. Eligible manuscripts compared PLEX or variants with conventional care for inducing proteinuria remission (PR) in rFSGS and were identified through MEDLINE and reference lists. Data were abstracted in parallel by two reviewers. Results. We detected 6 nonrandomized studies with 117 cases enrolled. In a random effects model, the pooled risk ratio for the composite endpoint of partial or complete PR was 0,38 in favour of PLEX (95% CI: 0,23-0,61). No statistical heterogeneity was observed among included studies (I (2) = 0%, p = 0,42). On average, 9-26 PLEX sessions were performed to achieve PR. Renal allograft loss due to recurrence was lower (range: 0%-67%) in patients treated with PLEX. Conclusion. Notwithstanding the inherent limitations of small, observational trials, PLEX appears to be effective for PR in rFSGS. Additional research is needed to further elucidate its optimal use and impact on long-term allograft survival.
Psychosocial Status of Liver Transplant Candidates in Iran and Its Correlation with Health-Related Quality of Life and Depression and Anxiety.
Banihashemi M, Hafezi M, Nasiri-Toosi M … +6 more , Jafarian A, Abbasi MR, Arbabi M, Abdi M, Khavarian M, Nejatisafa AA
J Transplant · 2015 · PMID 26649189 · Full text
Objectives. The study was aimed at providing a psychosocial profile for Iranian liver transplant candidates referred to an established liver transplantation program. Material and Methods. Patients assessed for liver tran...
Objectives. The study was aimed at providing a psychosocial profile for Iranian liver transplant candidates referred to an established liver transplantation program. Material and Methods. Patients assessed for liver transplant candidacy in Imam Khomeini Hospital (Tehran, Iran) between March 2013 and September 2014 were included. The following battery of tests were administered: Psychosocial Assessment of Candidates for Transplant (PACT), the Short-Form health survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). Results. Psychosocial assessment in 205 liver transplant candidates revealed significant impairments in several SF-36 domains; social functioning was the least and physical functioning was the most impaired domains. The prevalence of cases with probable anxiety and depressive disorders, according to HADS, was 13.8% and 5.6%, respectively. According to PACT, 24.3% of the assessed individuals were considered good or excellent candidates. In 11.2%, transplantation seemed poor candidate due to at least one major psychosocial or lifestyle risk factor. Poor candidate quality was associated with impaired health-related quality of life and higher scores on anxiety and depression scales (p < 0.05). Conclusions. Transplant programs could implement specific intervention programs based on normative databases to address the psychosocial issues in patients in order to improve patient care, quality of life, and transplant outcomes.
Influence of Deceased Donor and Pretransplant Recipient Parameters on Early Overall Kidney Graft-Survival in Germany.
Fischer-Fröhlich CL, Kutschmann M, Feindt J … +6 more , Schmidtmann I, Kirste G, Frühauf NR, Wirges U, Rahmel A, Schleicher C
J Transplant · 2015 · PMID 26539298 · Full text
Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-su...
Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 4411, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013-1.027] per year), donor size (0.985 [0.977-0.993] per cm), donor's creatinine at admission (1.002 [1.001-1.004] per µmol/L), donor treatment with catecholamine (0.757 [0.635-0.901]), and reduced graft-quality at procurement (1.549 [1.217-1.973]), as well as recipient age (1.012 [1.003-1.021] per year), actual panel reactive antibodies (1.007 [1.002-1.011] per percent), retransplantation (1.850 [1.484-2.306]), recipient's cardiovascular comorbidity (1.436 [1.212-1.701]), and use of IL2-receptor antibodies for induction (0.741 [0.619-0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care.
Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome.
Chaumont M, Racapé J, Broeders N … +9 more , El Mountahi F, Massart A, Baudoux T, Hougardy JM, Mikhalsky D, Hamade A, Le Moine A, Abramowicz D, Vereerstraeten P
J Transplant · 2015 · PMID 26448870 · Full text
Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined...
Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2-2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6-3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0-5.4]). Area under the curve of the ROC curve (0.77 [0.74-0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001). Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.
Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation.
Poldervaart RA, Laging M, Royaards T … +6 more , Kal-van Gestel JA, van Agteren M, de Klerk M, Zuidema W, Betjes MG, Roodnat JI
J Transplant · 2015 · PMID 26421181 · Full text
Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteris...
Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients (n = 101) were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (P < 0.001). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (P < 0.001). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate.
Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya.
Kubo MN, Kayima JK, Were AJ … +2 more , McLigeyo SO, Ogola EN
J Transplant · 2015 · PMID 26257920 · Full text
Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipi...
Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4-9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2-65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1-19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6-73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population.
Boceprevir-Based Triple Antiviral Therapy for Chronic Hepatitis C Virus Infection in Kidney-Transplant Candidates.
Mehawej M, Rostaing L, Alric L … +3 more , Del Bello A, Izopet J, Kamar N
J Transplant · 2015 · PMID 26257919 · Full text
Background. There are few data on the combination of (pegylated-) interferon- (Peg-IFN-) α, ribavirin, and first-generation direct-acting antiviral agents (DAAs). Our aim was to describe the efficacy and safety of Peg-IF...
Background. There are few data on the combination of (pegylated-) interferon- (Peg-IFN-) α, ribavirin, and first-generation direct-acting antiviral agents (DAAs). Our aim was to describe the efficacy and safety of Peg-IFN-α, ribavirin, and boceprevir in hemodialysis patients. Patients. Six hemodialysis patients, chronically infected by genotype-1 HCV, were given Peg-IFN-α (135 µg/week), ribavirin (200 mg/d), and boceprevir (2400 mg/d) for 48 weeks. Results. At initiation of antiviral therapy, median viral concentration was 5.68 (3.78-6.55) log IU/mL. HCV RNA was undetectable in four of the six patients at week 4 and in all patients at week 24. A breakthrough was observed in two patients between weeks 24 and 48, and a third patient stopped antiviral therapy between weeks 24 and 48 because of severe peripheral neuropathy. At week 48, HCV RNA was undetectable in three patients. Of these, two patients relapsed within a month after antiviral therapy was stopped. Hence, only one patient had a sustained virological response; he was a previous partial responder. Overall, anemia was the main side effect. Conclusion. A triple antiviral therapy based on Peg-IFN-α, ribavirin, and boceprevir is not optimal at treating hemodialysis patients with chronic HCV infection. Studies using new-generation drugs are required in this setting.
Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity.
Cosner D, Zeng X, Zhang PL
J Transplant · 2015 · PMID 26199736 · Full text
Tacrolimus (FK506) is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis i...
Tacrolimus (FK506) is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1) is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.
MicroRNAs in Kidney Transplantation: Living up to Their Expectations?
van den Akker EK, Dor FJ, IJzermans JN … +1 more , de Bruin RW
J Transplant · 2015 · PMID 26078872 · Full text
Since the discovery of microRNAs, ample research has been conducted to elucidate their involvement in an array of (patho)physiological conditions. Ischemia reperfusion injury is a major problem in kidney transplantation...
Since the discovery of microRNAs, ample research has been conducted to elucidate their involvement in an array of (patho)physiological conditions. Ischemia reperfusion injury is a major problem in kidney transplantation and its mechanism is still not fully known, nor is there an effective therapy. Furthermore, no biomarker is available to specifically measure (ischemic) damage after kidney transplantation or predict transplantation outcome. In this review, we summarize studies conducted on microRNAs in renal ischemia reperfusion injury and kidney transplantation. Although the number of publications on miRNAs in different areas of nephrology is increasing every year, only a limited number of reports that address the role of miRNAs in relation to ischemia reperfusion injury or kidney transplantation are available. All reports up to June 2014 on microRNAs in renal IRI, kidney transplantation, and renal allograft status were included. Design of the studies was highly variable and there was limited overlap between microRNAs found in these reports. No single microRNA expression pattern could be found, although multiple microRNAs involved in the immune response seem to be altered after ischemia reperfusion injury and kidney transplantation. Although there is a growing interest in microRNA research in kidney transplantation aiming to identify biomarkers and therapeutical targets, to date, no specific microRNA has been demonstrated to be applicable as either one, mostly because of lack of specificity. More systematical research is needed to determine whether microRNAs can be applied as biomarker, therapeutic target, or therapeutic agent in kidney transplantation.
Breakdown in the organ donation process and its effect on organ availability.
Razdan M, Degenholtz HB, Kahn JM … +1 more , Driessen J
J Transplant · 2015 · PMID 25949819 · Full text
Background. This study examines the effect of breakdown in the organ donation process on the availability of transplantable organs. A process breakdown is defined as a deviation from the organ donation protocol that may...
Background. This study examines the effect of breakdown in the organ donation process on the availability of transplantable organs. A process breakdown is defined as a deviation from the organ donation protocol that may jeopardize organ recovery. Methods. A retrospective analysis of donation-eligible decedents was conducted using data from an independent organ procurement organization. Adjusted effect of process breakdown on organs transplanted from an eligible decedent was examined using multivariable zero-inflated Poisson regression. Results. An eligible decedent is four times more likely to become an organ donor when there is no process breakdown (adjusted OR: 4.01; 95% CI: 1.6838, 9.6414; P < 0.01) even after controlling for the decedent's age, gender, race, and whether or not a decedent had joined the state donor registry. However once the eligible decedent becomes a donor, whether or not there was a process breakdown does not affect the number of transplantable organs yielded. Overall, for every process breakdown occurring in the care of an eligible decedent, one less organ is available for transplant. Decedent's age is a strong predictor of likelihood of donation and the number of organs transplanted from a donor. Conclusion. Eliminating breakdowns in the donation process can potentially increase the number of organs available for transplant but some organs will still be lost.
The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte globulin induction in liver transplant recipients that develop acute kidney injury in the early postoperative period.
Duhart BT, Ally WA, Krauss AG … +4 more , Hudson JQ, Eason JD, Rao V, Vanatta JM
J Transplant · 2015 · PMID 25861462 · Full text
Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We i...
Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was significantly (P < 0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P < 0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.
A Nationwide Assessment of the Burden of Urinary Tract Infection among Renal Transplant Recipients.
Becerra BJ, Becerra MB, Safdar N
J Transplant · 2015 · PMID 25810918 · Full text
Objective. Evaluate the prevalence and outcomes of urinary tract infection (UTI) among renal transplant recipients. Methods. A secondary analysis of the Nationwide Inpatient Sample 2009-2011 was conducted. Survey-weighte...
Objective. Evaluate the prevalence and outcomes of urinary tract infection (UTI) among renal transplant recipients. Methods. A secondary analysis of the Nationwide Inpatient Sample 2009-2011 was conducted. Survey-weighted multivariable regression analyses were used to examine the impact of UTI on transplant complications, total charges, and length of stay. Results. A total of 1,044 renal transplant recipients, representing a population estimate of 49,862, were included in the study. UTI was most common in transplant recipients with hypertension (53%) and prevalence was noted to be 28.2 and 65.9 cases per 1,000 for men and women, respectively. UTI increased the likelihood of transplant complications (182% for men, 169% for women). Total charges were 28% higher among men as compared to 22% among women with UTI. Such infection also increased the length of stay by 87% among men and 74% among women. Discussion. UTI in renal transplant recipients was associated with prolonged length of stay, total charges, and increased odds of transplant complications. Interventions to prevent UTI among such patients should be a priority area for future research and practice.
Risk-adjusted analysis of relevant outcome drivers for patients after more than two kidney transplants.
Kousoulas L, Vondran FW, Syryca P … +3 more , Klempnauer J, Schrem H, Lehner F
J Transplant · 2015 · PMID 25722883 · Full text
Renal transplantation is the treatment of choice for patients suffering end-stage renal disease, but as the long-term renal allograft survival is limited, most transplant recipients will face graft loss and will be consi...
Renal transplantation is the treatment of choice for patients suffering end-stage renal disease, but as the long-term renal allograft survival is limited, most transplant recipients will face graft loss and will be considered for a retransplantation. The goal of this study was to evaluate the patient and graft survival of the 61 renal transplant recipients after second or subsequent renal transplantation, transplanted in our institution between 1990 and 2010, and to identify risk factors related to inferior outcomes. Actuarial patient survival was 98.3%, 94.8%, and 88.2% after one, three, and five years, respectively. Actuarial graft survival was 86.8%, 80%, and 78.1% after one, three, and five years, respectively. Risk-adjusted analysis revealed that only age at the time of last transplantation had a significant influence on patient survival, whereas graft survival was influenced by multiple immunological and surgical factors, such as the number of HLA mismatches, the type of immunosuppression, the number of surgical complications, need of reoperation, primary graft nonfunction, and acute rejection episodes. In conclusion, third and subsequent renal transplantation constitute a valid therapeutic option, but inferior outcomes should be expected among elderly patients, hyperimmunized recipients, and recipients with multiple operations at the site of last renal transplantation.
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