Irish Renal Transplant Research Articles

Risk factors and long-term consequences of new-onset diabetes after renal transplantation.

New-onset diabetes after transplant (NODAT) confers risk of diabetes-related complications as well as a threat to graft function and overall patient survival. The reported incidence of NODAT varies from 14 to 37% in renal transplant recipients worldwide; however, NODAT is yet to be studied in the Irish renal transplant population. Primary aims of this project were to estimate the incidence, to determine associated risk factors and to assess the long-term consequences of NODAT on graft survival and patient survival in the Irish renal transplant population. Retrospective data collection of 415 renal transplant recipients over a 12-year period was performed to record presence of NODAT, patient characteristics and perioperative management. Preoperative screening was reviewed in a subgroup of patients to determine concordance with the International Consensus Guidelines. Statistical analysis was performed using Kaplan-Meier survival functions estimating NODAT detection over time, graft and patient survival. Risk factor association was determined using Cox proportional-hazards models. NODAT incidence was 10.2% in the first 5years of post-transplant. Risk factors for developing NODAT were recipient age and body weight. Risk of NODAT was highest in the first year of post-transplant and conferred decreased patient survival; however, it did not significantly affect graft survival. Only seven patients of a subgroup of 21 patients who developed NODAT had preoperative testing for diabetes. NODAT incidence in the Irish renal transplant population is slightly below international figures. This project has highlighted current deficits in the national transplant guidelines for the detection of NODAT and NODAT-related risk factors.

Thirty-seven-year Population-based Study of Colorectal Cancer Rates in Renal Transplant Recipients in Ireland

BackgroundRenal transplantation is associated with an increased risk of neoplasia, including colorectal cancer (CRC). Advances in surgical techniques and immunosuppressive medications have resulted in increased survival rates of both patients and grafts, but the incidence of CRC in the Irish renal transplant population is currently unknown. The aim of this study is to review the incidence of CRC in the Irish renal transplant population and compare it to the general population. MethodsA retrospective review of a prospectively maintained database of all renal transplant recipients in Ireland between January 1980 and July 2017 was performed. ResultsThirty-three out of 4230 transplant recipients (men = 20, women = 13) developed CRC subsequent to transplantation and were eligible for inclusion in the series. The mean age at transplantation was 51.5 years, with patients developing CRC on average 10.9 years post-transplantation; 6.1% (n = 2/33) had stage IV disease at diagnosis. The majority of patients (87.8%) had a pathologic T stage of T3/T4 and 45.5% had involvement of locoregional lymph nodes (N1/N2); 42.4% also had a mucinous component at histopathologic assessment. The incidence of CRC was higher in the transplant population compared to the general population. ConclusionThis is the first population-based assessment of CRC development in the Irish renal transplant population. Our data suggest that Irish transplant recipients have an increased risk of being diagnosed with a more advanced tumor than the general population, with most being diagnosed almost a decade after transplantation. This highlights the need for increased awareness among patients and clinicians and the potential need for coordinated lifelong surveillance of this patient population to ensure early detection and treatment.

Posttransplant Lymphoproliferative Disorders in Irish Renal Transplant Recipients: Insights From a National Observational Study.

Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients. Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population. We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified. We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.

Outcomes of kidney transplantation in Alport syndrome compared with other forms of renal disease

Introduction: Alport syndrome is an inherited renal disease characterized by hematuria, renal failure, hearing loss and a lamellated glomerular basement membrane. Patients with Alport syndrome who undergo renal transplantation have been shown to have patient and graft survival rates similar to or better than those of patients with other renal diseases.Methods: In this national case series, based in Beaumont Hospital Dublin, we studied the cohort of patients who underwent renal transplantation over the past 33 years, recorded prospectively in the Irish Renal Transplant Registry, and categorized them according to the presence or absence of Alport syndrome. The main outcomes assessed were patient and renal allograft survival.Results: Fifty-one patients diagnosed with Alport syndrome in Beaumont Hospital received 62 transplants between 1982 and 2014. The comparison group of non-Alport patients comprised 3430 patients for 3865 transplants. Twenty-year Alport patient survival rate was 70.2%, compared to 44.8% for patients with other renal diseases (p = .01). Factors associated with patient survival included younger age at transplantation as well as differences in recipient sex, donor age, cold ischemia time, and episodes of acute rejection. Twenty-year graft survival was 46.8% for patients with Alport syndrome compared to 30.2% for those with non-Alport disease (p = .11).Conclusions: Adjusting for baseline differences between the groups, patients with end-stage kidney disease (ESKD) due to Alport syndrome have similar patient and graft survival to those with other causes of ESKD. This indicates that early diagnosis and management can lead to favorable outcomes for this patient cohort.

Transplant Outcomes in Patients with Idiopathic Membranous Nephropathy

Background. The natural history of idiopathic membranous nephropathy and recurrent disease in transplants is variable. We performed a retrospective cohort study of renal transplant recipients with a primary diagnosis of idiopathic membranous nephropathy. We aimed to establish patterns of disease recurrence and to identify factors associated with disease recurrence. Methods. We accessed the Irish renal transplant database to identify patients with biopsy-proven idiopathic membranous nephropathy in receipt of a renal transplant between 1982 and 2010. A detailed medical chart review was performed in all cases, and a senior renal histopathologist reviewed all histology specimens. Results. The outcomes of 32 patients, in receipt of 36 grafts, are reported. There was a male preponderance (n = 29). Significant graft dysfunction, directly attributable to recurrent disease, was evident in 31% of cases at 10 years. There was no significant association between time on dialysis, HLA mismatch, occurrence of rejection, and the development of recurrent membranous disease. One patient was retransplanted twice; all three grafts were lost to aggressive recurrent membranous disease. Conclusions. It remains difficult to identify those that will develop recurrent membranous nephropathy. Almost one third of patients in this cohort developed clinically significant recurrent disease at 10 years.

Twenty-Year Survivors of Kidney Transplantation

There have been few studies of patients with renal allografts functioning for more than 20 years. We sought to identify clinical factors associated with ultra long-term (>20 year) renal allograft survival and to describe the clinical features of these patients. We performed a retrospective analysis of the Irish Renal Transplant Database and included 1174 transplants in 1002 patients. There were 255 (21.74%) patients with graft function for 20 years or more. Multivariate analysis identified recipient age (HR 1.01, CI 1.01-1.02), gender (male HR 1.25, CI 1.08-1.45), acute rejection (HR 1.26, CI 1.09-1.45) and transplant type (living related donor vs. deceased donor) (HR 0.52, CI 0.40-0.66) as significantly associated with long-term graft loss. Median serum creatinine was 115 μmol/L. The 5-year graft survival in 20-year survivors was 74.7%. The mean age at death was 62.7 years (±10.6). The most common causes of death were cardiovascular disease and malignancy. The two major causes of graft loss were death (with function) and interstitial fibrosis/tubular atrophy. Comorbidities included skin cancer (36.1%), coronary heart disease (17.3%) and other malignancies (14.5%). This study identifies factors associated with long-term allograft survival and a high rate of morbidity and early mortality in long-term transplant recipients.

Analysis of waiting times on Irish renal transplant list

A number of recipient variables have been identified which influence waiting list times for a renal allograft. The aim of this study was to evaluate these factors in the Irish population. We examined patients accepted onto the transplant list from January 1, 2000 until December 31, 2005. Inclusion criteria were adults listed for kidney only, deceased donor transplants. We included patients previously transplanted. Patients were censored, but still included in the analysis, if they died while on the list, permanently withdrew from the list or if they were not transplanted at the time of the study. There were a total of 984 patients accepted onto the waiting list during the study period, of which 745 of these were transplanted. Factors significantly associated with longer waiting times included age above 50 yr, blood group O and high peak panel reactive antibodies level. Gender and patient body mass index were not associated with longer waiting times. We have identified factors associated with a longer waiting time on the Irish cadaveric renal transplant list. This information can help our patients make informed decisions regarding likely waiting times and the merits of living related transplantation.

MDRD-Estimated GFR at One Year Post-Renal Transplant Is a Predictor of Long-Term Graft Function

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr1yr) and MDRD estimated glomerular filtration rate measured at one year (eGFRMDRD1yr) as predictors of graft survival.Data on 1,110 patients who received a renal transplant between 1989 and 2005 were extracted from the Irish Renal Transplant Registry. The study group was divided into quartiles of patient numbers according to SCr1yr and eGFRMDRD1yr. Kaplan-Meier estimates of the primary end-point graft survival were constructed for each quartile.Additionally, a Cox Regression restricted cubic spline model was performed for both eGFRMDRD1yr and SCr1yr. Both overall graft outcome and outcome censored for death with a functioning graft (CDWFG) were used as endpoints. Cox regression analysis was performed along with tests for the proportionality assumption to compare the predictive value of eGFRMDRD1yrand SCr1yr.Both eGFRMDRD1yr and SCr1yr were independently associated with long-term renal transplant survival. eGFRMDRD1yr and SCr1yr had similarly strong associations with long-term outcome when the quartile variables were compared using the Bayesian Information Criterion method. The Cox regression restricted cubic spline modeling demonstrated that an eGFRMDRD1yr value < 27 mLs/min/1.73m2 and a SCr1yr value > 229 μmol/L were associated with poor graft survival.

Impaired renal allograft, but not patient survival, in patients with antibodies to hepatitis C virus

The impact of hepatitis C virus (HCV) infection in renal transplant patients is controversial and there are no data on the outcome of renal transplantation in this sub-group of Irish patients. To examine the outcome of renal transplantation in patients with hepatitis C. We examined the outcome of first grafts from renal transplant patients with hepatitis C antibody positive and compared them to a control group. During this period, 24 HCV positive patients received 33 grafts. All were treated with standard immunosuppression. Graft survival rate was less in the HCV positive cases (p=0.0087). Graft survival at 1 year was 75% in the HCV positive group versus 85% in the HCV negative group, 40% versus 62% at 5 years and 14% compared with 40% at 10 years. Patient survival was similar in both groups (p=0.78). Patient survival at 1 year was 96% versus 94%, 87% versus 80% at 5 years and 70% in both groups at 10 years. In the Irish renal transplant population, the presence of hepatitis C antibodies, before or after transplantation is associated with worse long-term graft, but not patient survival.

Pretransplant Cardiac Investigations in the Irish Renal Transplant Population—The Effectiveness of Our Current Screening Techniques in Predicting Cardiac Events

Background. Coronary artery disease (CAD) is prevalent among endstage renal failure patients and remains the major cause of mortality following renal transplantation. Death with a functioning transplant institute remains the most common cause of kidney graft failure. In this study we attempt to evaluate the effectiveness of the clinical history and current screening techniques available in predicting posttransplant CAD and also assess the role of coronary angiography as a pretransplant screening technique. Methods. Clinical data of 190 renal transplant patients was analyzed. Any clinical history of cardiac disease and all preoperative cardiac screening data was recorded for each patient. The study endpoints were the subsequent development of myocardial infarction (MI), undergoing coronary artery bypass graft (CABG) or death. Results. Factors that were significantly associated with reaching a study end‐point included: age at transplant [Hazard Ratio (HR) 1.91, P < 0.001], history of heart failure (HR 8.22, P < 0.001), presence of CAD on coronary angiography (HR 5.55, P = 0.033), anterior Q wave on electrocardiograph {ECG} (HR 8.6, P < 0.001), carotid artery disease (HR 3.74, P = 0.030) and history of a cerebrovascular accident (HR of 4.32, P = 0.008). The screening techniques of exercise stress testing and echocardiography were not conclusive as predictive variables of outcome. Conclusion. Clinical history and ECG results are good, practical and low‐cost screening methods. In our study exercise stress testing and echocardiography were found to be of limited value. Coronary angiography is appropriate in certain high‐risk groups but not necessary as part of screening in all potential renal transplant recipients.

Pregnancy in Irish renal transplant recipients in the cyclosporine era.

The effect of renal transplantation on pregnancy in Irish women not receiving CyA has been reported previously. To examine all pregnancies occurring in Irish female renal transplant recipients since the introduction of CyA. Using a community based approach, we identified 29 pregnancies in 19 women, aged between 16 and 45, mean age 30.3 years. These pregnancies ended in four miscarriages (13%), two intra-uterine deaths (6.9%) and 23 live births (79.3%). Of these live births, 73.9% were premature (< or = 36 weeks) and 65.2% were of low birth weight (< 2500 g). Admission to the neonatal intensive care was necessary in 61%, and two babies (8.7%) died in the neonatal period. Mean gestational age was 34 weeks, and mean birth weight was 2190 g. There was no change in graft function during pregnancy, with a small rise in serum creatinine post-partum (+9.64 mumol/L). The renal graft failed in three women (15.8%) by the end of the follow-up period. Compared with the precyclosporine era, the live birth rate was higher (79.3% versus 58%) with a trend towards lower birth weight and shorter gestation. Renal transplantation with CyA use is not a contraindication to pregnancy, but it is associated with increased risk, especially when the serum creatinine is > 175 mumol/L.

Skin cancer in an Irish renal transplant population.

One hundred and forty-nine renal transplant patients attending 2 centres in Dublin were examined. Twelve patients (8.1%) were found to have cutaneous malignancy while dysplastic lesions (premalignant and/or malignant) were identified in 34 (22.8%). The prevalence of cutaneous malignancy in this study is substantially greater than that of previous Irish studies. The introduction of cyclosporin A (CyA) as a new and more effective immunosuppressive agent in renal transplantation may in part explain this increase.