Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.

Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Randomized clinical trial to determine the effectiveness of CO-oximetry and anti-smoking brief advice in a cohort of kidney transplant patients who smoke.

Background: measure the efficacy of exhaled carbon monoxide (CO) measurement plus brief advisory sessions to reduce smoking exposure and smoking behaviour in kidney transplant recipients. Methods: Randomized, controlled, open-label clinical trial at a Spanish hospital.Smoking kidney transplant recipients giving their consent to participate were randomized to control (brief advice, n=63) or intervention group (brief advisory session plus measuring exhaled CO, n=59). Measurements: Sociodemographic characteristics, cardiovascular risk factors, treatment, rejection episodes, infections, self-reported smoking, drug use, level of dependence and motivation to stop smoking (Fagerström's and Richmond's test) and stage of change (Prochaska and DiClemente's Stages). Efficacy was assessed at 3, 6, 9 and 12 months as: cotinine test, CO levels in exhaled air, nicotine dependence, motivational stages of change, motivation to stop smoking, pattern of tobacco use and smoking cessation rates. Logistic regression models were computed. Results: At 12 months of follow-up, differences were found in exhaled CO between the intervention and control group(6.1±6.8vs.10.2±9.7ppm;p=0.028). Carboxyhemoglobin levels were lower in the intervention group as well as the positive cotinine test (1.2±1.2%vs.2.0±2.4%;p=0.039),(53.4%vs.74.2%). At 12 months, intervention reduces the probability of a positive urine test by 28%. Conclusions: Co-oximetry is a clinically relevant intervention for reduction of tobacco exposure in kidney transplant recipients.

Trasplante renal de donante vivo ABO incompatible. Estudio de 48 pacientes tras desensibilización / ABO-incompatible living-donor kidney transplantation: Study of 48 patients after desensitisation

ANTECEDENTES: El trasplante renal de donante vivo ABO incompatible era considerado una contraindicación absoluta. Desde hace años, se realiza con buenos resultados. OBJETIVO: Nuestro objetivo es mostrar los resultados de este tipo de trasplante realizado en nuestro hospital. MÉTODOS: Estudiamos 48 pacientes con una edad media de 50,9 ± 10,9 años. Seguimiento 44,6 ± 30,9 meses. Acondicionamiento: rituximab 375mg/m2, tacrolimus, micofenolato mofetilo o micofenolato sódico, prednisona, plasmaféresis/inmunoadsorción e inmunoglobulina intravenosa. Títulos de isoaglutininas aceptados para trasplantar: IgG e IgM inferiores a 1:8. RESULTADOS: Isoaglutininas preproceso: IgG 1:124 ± 1:140, IgM 1:77 ± 1:55. Tras 6 ± 3 sesiones, la IgG descendió a < 1:8 en 47 pacientes, a<1:16 en uno; la IgM fue < 1:8 en todos. Veinticuatro pacientes (50%) presentaron hematoma, 7 reintervención (14,6%) y 29 (60%) necesitaron transfusión. Al quinto año presentaron rechazo agudo 5 pacientes (8,7%), CMV 9 (19,7%), viremia BK 5 (12,4%), diabetes postrasplante 10 (23,4%), linfocele 3 (6,4%). La supervivencia del paciente fue del 97,1% al quinto año y la del injerto, del 95,7% al año y del 93% al quinto año. Pérdida de injerto: trombosis (n = 1), rechazo mixto (n = 1) y exitus (n=2). La creatinina al año y a los 3 años fue de 1,4 ± 0,4 mg/dl y de 1,3 ± 0.3 mg/dl al quinto año. La proteinuria al año, a los 3 y a los 5 fue de 0,2 ± 0,2 g/24 h. CONCLUSIONES: El trasplante renal de donante vivo ABO incompatible tras acondicionamiento con rituximab, plasmaféresis/inmunoadsorción e inmunoglobulinas es una opción válida y ofrece excelentes resultados de supervivencia, con una baja incidencia de rechazo agudo sin aumento de complicaciones infecciosas. Se evidencia una mayor tendencia al sangrado postoperatorio

BACKGROUND: ABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes. OBJECTIVE: Our aim was to show the results obtained with this technique in our hospital. METHODS: Forty-eight patients with a mean age of 50.9 ± 10.9 years were included. Follow-up was 44.6 ± 30.9 months. Conditioning: rituximab 375 mg/m2, tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titres for transplantation: < 1:8. RESULTS: Pre-process IgG titre 1:124 ± 1:140, IgM titre 1:77 ± 1:55. After 6 ± 3 sessions, IgG decreased to < 1:8 in 47 patients and to < 1:16 in one. IgM was < 1:8 in all cases. Twenty-four patients (50%) had haematoma, 7 re-intervention (14.6%), 29 (60%) required transfusion. At 5 years, acute rejection had occurred in 5 cases (8.7%), CMV infection in 9 (19.7%), BK viraemia in 5 (12.4%), post-transplant diabetes in 10 (23.4%) and lymphocele in 3 (6.4%). Patient survival was 97.1% at 5 years and graft survival 95.7% at one year and 93% at 5 years. Causes of graft loss: thrombosis (n = 1); mixed rejection (n = 1); and death (n = 2). Serum creatinine levels were 1.4 ± 0.4 mg/dl at one and 3 years and 1.3 ± 0.3 mg/dl at 5 years. Proteinuria was 0.2 ± 0.2 g/24 h at one, 3 and 5 years. CONCLUSIONS: ABO-incompatible living-donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes. There is a low incidence of acute rejection and no increase in infectious complications. An increased tendency for postoperative bleeding was found

ABO-incompatible living-donor kidney transplantation: Study of 48 patients after desensitisation. / Trasplante renal de donante vivo ABO incompatible. Estudio de 48 pacientes tras desensibilización.

BACKGROUND: ABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes. OBJECTIVE: Our aim was to show the results obtained with this technique in our hospital. METHODS: Forty-eight patients with a mean age of 50.9±10.9 years were included. Follow-up was 44.6±30.9 months. Conditioning: rituximab 375mg/m2, tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titres for transplantation:<1:8. RESULTS: Pre-process IgG titre 1:124±1:140, IgM titre 1:77±1:55. After 6±3 sessions, IgG decreased to<1:8 in 47 patients and to<1:16 in one. IgM was<1:8 in all cases. Twenty-four patients (50%) had haematoma, 7 re-intervention (14.6%), 29 (60%) required transfusion. At 5 years, acute rejection had occurred in 5 cases (8.7%), CMV infection in 9 (19.7%), BK viraemia in 5 (12.4%), post-transplant diabetes in 10 (23.4%) and lymphocele in 3 (6.4%). Patient survival was 97.1% at 5 years and graft survival 95.7% at one year and 93% at 5 years. Causes of graft loss: thrombosis (n=1); mixed rejection (n=1); and death (n=2). Serum creatinine levels were 1.4±0.4mg/dl at one and 3 years and 1.3±0.3mg/dl at 5 years. Proteinuria was 0.2±0.2g/24h at one, 3 and 5 years. CONCLUSIONS: ABO-incompatible living-donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes. There is a low incidence of acute rejection and no increase in infectious complications. An increased tendency for postoperative bleeding was found.

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

BACKGROUND: The 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. METHODS: An 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). RESULTS: The 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. CONCLUSIONS: This 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 randomized clinical trial to determine the effectiveness of CO-oximetry and anti-smoking brief advice in a cohort of kidney transplant patients who smoke: study protocol for a randomized controlled trial.

BACKGROUND: The cardiovascular risk in renal transplant patients is increased in patients who continue to smoke after transplantation. The aim of the study is to measure the effectiveness of exhaled carbon monoxide (CO) measurement plus brief advisory sessions, in comparison to brief advice, to reduce smoking exposure and smoking behavior in kidney transplant recipients who smoke. The effectiveness will be measured by: (1) abandonment of smoking, (2) increase in motivation to stop smoking, and (3) reduction in the number of cigarettes smoked per day. DESIGN: a randomized, controlled, open clinical trial with blinded evaluation. SCOPE: A Coruña Hospital (Spain), reference to renal transplantation in the period 2012-2015. INCLUSION CRITERIA: renal transplant patients who smoke in the precontemplation, contemplation or preparation stages according to the Prochaska and DiClemente's Stages of Change model, and who give their consent to participate. EXCLUSION CRITERIA: smokers attempting to stop smoking, patients with terminal illness or mental disability that prevents them from participating. RANDOMIZATION: patients will be randomized to the control group (brief advisory session) or the intervention group (brief advisory session plus measuring exhaled CO). The sample target size is n = 112, with 56 patients in each group. Allowing for up to 10 % loss to follow-up, this would provide 80 % power to detect a 13 % difference in attempting to give up smoking outcomes at a two-tailed significance level of 5 %. MEASUREMENTS: sociodemographic characteristics, cardiovascular risk factors, treatment, rejection episodes, infections, self-reported smoking habit, drug use, level of dependence (the Fagerström test), stage of change (Prochaska and DiClemente's Stages of Change model), and motivation to giving up smoking (the Richmond test). RESPONSE: the effectiveness will be evaluated every 3, 6, 9 and 12 months as: pattern of tobacco use (self-reported tobacco use), smoking cessation rates, carbon monoxide (CO) levels in exhaled air measured by CO-oximetry, urinary cotinine tests, nicotine dependence (Fagerström test), motivational stages of change (Prochaska and DiClemente's stages) and motivation to stop smoking (the Richmond test). ANALYSIS: descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. ETHICS: informed consent of the patients and Ethical Review Board was obtained (code 2011/061). DISCUSSION: Tobacco is a modifiable risk factor that increase the risk of morbidity and mortality in kidney transplant recipients. If effectiveness of CO-oximetry is confirmed to reduce tobacco exposure, we would have an intervention that is easy to use, low cost and with great implications about cardiovascular risk prevention in these patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16615772 . EudraCT number: 2015-002009-12.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Incidence of cardiovascular events after kidney transplantation and cardiovascular risk scores: study protocol.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of death after renal transplantation. Not only conventional CVD risk factors, but also transplant-specific risk factors can influence the development of CVD in kidney transplant recipients. The main objective of this study will be to determine the incidence of post-transplant CVD after renal transplantation and related factors. A secondary objective will be to examine the ability of standard cardiovascular risk scores (Framingham, REGICOR, SCORE, and DORICA) to predict post-transplantation cardiovascular events in renal transplant recipients, and to develop a new score for predicting the risk of CVD after kidney transplantation. METHODS/DESIGN: Observational prospective cohort study of all kidney transplant recipients in the A Coruna Hospital (Spain) in the period 1981-2008 (2059 transplants corresponding to 1794 patients). The variables included will be: donor and recipient characteristics, chronic kidney disease-related risk factors, pre-transplant and post-transplant cardiovascular risk factors, routine biochemistry, and immunosuppressive, antihypertensive and lipid-lowering treatment. The events studied in the follow-up will be: patient and graft survival, acute rejection episodes and cardiovascular events (myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances and peripheral vascular disease). Four cardiovascular risk scores were calculated at the time of transplantation: the Framingham score, the European Systematic Coronary Risk Evaluation (SCORE) equation, and the REGICOR (Registre Gironi del COR (Gerona Heart Registry)), and DORICA (Dyslipidemia, Obesity, and Cardiovascular Risk) functions. The cumulative incidence of cardiovascular events will be analyzed by competing risk survival methods. The clinical relevance of different variables will be calculated using the ARR (Absolute Risk Reduction), RRR (Relative Risk Reduction) and NNT (Number Needed to Treat). The ability of different cardiovascular risk scores to predict cardiovascular events will be analyzed by using the c index and the area under ROC curves. Based on the competing risks analysis, a nomogram to predict the probability of cardiovascular events after kidney transplantation will be developed. DISCUSSION: This study will make it possible to determine the post-transplant incidence of cardiovascular events in a large cohort of renal transplant recipients in Spain, to confirm the relationship between traditional and transplant-specific cardiovascular risk factors and CVD, and to develop a score to predict the risk of CVD in these patients.

Association of bladder adenocarcinoma and BK virus infection in a pancreatico-renal transplant recipient.

Viral infection has been related to post-transplantation tumour development, particularly Epstein-Barr virus, human papillomavirus, hepatitis B and C viruses, and herpes virus 8. Recently, BK virus (BKV) has emerged as an important cause of tumour formation in solid organ transplant recipients. BKV oncogenic potential relates to the ability to inactivate the functions of tumour suppression proteins p53 and pRB family, and induction of chromosomal aberrations. We report a case of urinary bladder adenocarcinoma in a pancreatico-renal transplant recipient which was diagnosed 2 years after BKV infection. Immunohistochemical staining for SV-40 was positive in neoplastic cells but negative in non-neoplastic cells.

Validity and reliability of the SF-36 questionnaire in patients on the waiting list for a kidney transplant and transplant patients.

BACKGROUND/AIMS: The aim of this study is to explore the validity and reliability of the health-related quality of life SF-36 questionnaire in patients undergoing renal replacement therapy. METHODS: A multicenter descriptive transversal study was carried out in Galicia, Spain, with patients undergoing renal replacement therapy. The tool used to measure the health-related quality of life was the authorized Spanish version of the 'SF-36' generic health questionnaire. The internal consistency of this survey was determined by means of interscale correlations and Cronbach's alpha statistic. Validity was examined with a principal component exploratory factor analysis with Varimax rotation. RESULTS: A total of 213 patients waiting for a kidney transplant and 72 recipients with a functioning renal transplant were studied. All the interscale correlations were positive and significant. The overall statistical value for Cronbach's alpha was equal to 0.91 (95% CI: 0.91-0.94) and in all domains this value ranged from 0.7 to 0.92. The factor analysis identified 8 factors that explain 66.6% of the variance, 5 of which consisted of the same structure as 5 factors (domains) of the theoretical model. CONCLUSION: The SF-36 questionnaire is also a reliable and valid tool when used to measure the quality of life of patients undergoing renal replacement therapy.