Search

Solid organ transplantation is associated with increased risk of non-melanoma skin cancer. Studies with short follow up times have suggested a reduced occurrence of these cancers in recipients treated with mammalian target of rapamycin inhibitors as maintenance immunosuppression. We aimed to describe the occurrence of skin cancers in renal and liver transplant recipients switched from calcineurin inhibitor to sirolimus-based regimes. We performed a retrospective study of sirolimus conversion within the Irish national kidney and liver transplant programs. These data were linked with the National Cancer Registry Ireland to determine the incidence of NMSC among these recipients. The incidence rate ratio (IRR) for post versus pre-conversion NMSC rates are referred in this study as an effect size with [95% confidence interval]. Of 4,536 kidney transplants and 574 liver transplants functioning on the 1 January 1994 or transplanted between 1 January 1994 and 01 January 1994 and 01 January 2015, 85 kidney and 88 liver transplant recipients were transitioned to sirolimus-based immunosuppression. In renal transplants, the rate of NMSC was 131 per 1000 patient years pre-switch to sirolimus, and 68 per 1000 patient years post switch, with adjusted effect size of 0.48 [0.31 − 0.74] (p =.001) following the switch. For liver transplant recipients, the rate of NMSC was 64 per 1,000 patient years pre-switch and 30 per 1,000 patient years post switch, with an adjusted effect size of 0.49 [0.22 − 1.09] (p.081). Kidney transplant recipients were followed up for a median 3.4 years. Liver transplants were followed for a median 6.6 years. In this study, the conversion of maintenance immunosuppression from calcineurin inhibitors to mTOR inhibitors for clinical indications did appear to reduce the incidence of NMSC in kidney and liver transplant recipients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Transient ST-segment depression measured on ambulatory ECG monitors has been described as representing silent ischemia. Patients who demonstrate silent ischemia have been reported to show increased mortality compared to patients without silent ischemia. We undertook this study to determine if the correction of anemia in End Stage Renal Disease (ESRD) patients from(± = standard deviation) 30 ± 3 to 42 ± 3 with the use of Epoetin alfa would result in decreased silent ischemia in patients with clinically evident ischemic heart disease or congestive heart failure. METHODS: Thirty one ESRD patients with congestive heart failure or patients with clinically-evident ischemic heart disease were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42 ± 3% and patients in Group B were maintained with a hematocrit of 30 ± 3% throughout the course of the study. All patients had a 24 hour Holter monitor recording at baseline and at 28 weeks after randomization (when they had reached their target hematocrit). Significant silent ischemia was considered to be present if patients demonstrated at least 60 seconds of ≥ 1 mm ST segment depression. RESULTS: Fifteen patients were randomized to Group A and 16 patients were randomized to Group B. The mean hematocrit increased in group A from 29.1 ± 2.4% to 40.8 ± 5.2% after 30 weeks. The mean hematocrit in Group B remained stable at 30 ± 3% throughout the course of the study. Ten patients demonstrated silent ischemia at baseline. At follow up patients in group A demonstrated a mean of 1.7 ± 4.9 minutes of ischemia compared to 1.1 ± 3.4 minutes in group B. These were not significantly different. A similar number of patients in group A and Group B required adjustments in their anti-anginal medication during the course of the study. CONCLUSION: It is possible to increase hematocrit to near... [ABSTRACT FROM AUTHOR]

Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPARα, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation. [ABSTRACT FROM AUTHOR]

Aim: Long-term survival of renal allografts has improved over the last 20 years. However, less is known about current expectations for long-term allograft function as determined by estimated glomerular filtration rate (eGFR). The aim of this study was to investigate factors which affect graft function at 5 years' post-renal transplantation. The statistically significant factors were then used to construct a predictive model for expected eGFR at five years' post-transplant. Methods: We retrospectively reviewed all adult patients who received a renal transplant in the Republic of Ireland between 1990 and 2004. Data collected included era of transplantation (1990-1994, 1995-1999, 2000-2004), donor and recipient age and gender, number of human leucocyte antigen mismatches, cold ischemia time (CIT), number of prior renal transplants, immunosuppressive regimen used and acute rejection episodes. Estimated GFR was calculated at 5 years after transplantation from patient data using the Modified Diet in Renal Disease (MDRD) equation. Consecutive sampling was used to divide the study population into two equal unbiased groups of 489 patients. The first group (derivation cohort) was used to construct a predictive model for eGFR five years' post-transplantation, the second (validation cohort) to test this model. Results: Nine hundred and seventy eight patients were analyzed. The median age at transplantation was 43 years (range 18-78) and 620 (63.4%) were male. One hundred and seventy five patients (17.9%) had received a prior renal transplant. Improved eGFR at five years' post-transplantation was associated with tacrolimus-based combination immunosuppression, younger donor age, male recipient, absence of cytomegalovirus disease and absence of acute rejection episodes as independently significant factors ( p < 0.05). The predictive model developed using these factors showed good correlation between predicted and actual median eGFR at five years. The model explained 20% of eGFR variability. The validation model findings were consistent with the derivation model (21% variability of eGFR explained by model using same covariates on new data). Conclusion: The predictive model we have developed shows good correlation between predicted and actual median eGFR at five years' post-transplant. Applications of this model include comparison of current and future therapy options such as new immunosuppressive regimens. [ABSTRACT FROM AUTHOR]

Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO®®, was given at a dose of 40 µµg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU//mL == patient immune, (2) a titer level 10--99 mIU//mL == give a booster dose and recheck level 2 months later, and (3) 0 ££ 10 mIU//mL == repeat vaccination course using a different vaccine, Engerix-B®®. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40%% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64%% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82%% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin ( p == 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients. [ABSTRACT FROM AUTHOR]

Secondary hyperparathyroidism and abnormal calcium/phosphate balance are common complications of ESRD and significant cardiovascular risk factors. It has also been demonstrated that malnourished dialysis patients have a much higher mortality than well-nourished patients. There is a lack of research looking at combined mortality with altered mineral metabolism and a low serum albumin. Using our renal database, we analyzed outcomes on 1,007 chronic dialysis patients, commencing dialysis between January 1990 and December 2004. The association between median values of serum phosphate, calcium, albumin (between three and six months post-commencement of dialysis), and long-term survival was examined. Cox proportional hazards models were used to determine the combined effects of these variables on patient outcome. The results showed that 18% of patients had serum phosphorous >1.8 mmol/L (5.5 g/dL), and the five-year survival of these patients was 48.4% compared with 58.6% for those with a serum phosphorous <1.8 mmol/L (p = 0.047). For serum albumin, 34.9% had a value <35 g/L, and this group also had a highly significant risk of increased mortality (p < 0.001). When combined with corrected calcium, 40.9% of patients reached all three target levels and had the greatest long-term survival (five-year survival of 62.5% for all three targets reached, compared to 30.7% for 0 or 1 targets reached). Poor control of calcium/phosphorous balance appears to have long-term deleterious effects on patient survival in ESRD patients. This risk of death is increased by poor serum albumin levels reflecting inadequate nutrition. [ABSTRACT FROM AUTHOR]

It is recognized that cytomegalovirus (CMV) infection in transplant recipients may lead to graft loss. Prophylaxis with acyclovir has therefore gained widespread acceptance, but the debate on whether this intervention improves long term graft survival continues. All patients who received renal grafts at the National Renal Transplant Centre, Dublin, between January 1992 and December 1999 were retrospectively analyzed. During this time period, patients who were CMV positive and/or had received grafts from CMV-positive donors were administered prophylactic oral acyclovir 800 mg thrice daily, adjusted for calculated creatinine clearance, from the first day post-transplantation. This treatment was continued for three months unless the graft failed or the patient developed CMV disease or died. Graft and patient outcomes were compared in recipients who received acyclovir with those who did not. Over the study period, 935 patients received renal transplants in our center, of whom 487 were administered acyclovir. The incidence of CMV disease was 3.3 cases per 100 patients per annum in those who required prophylaxis. Despite prophylaxis, graft outcomes were found to be significantly worse (p value < 0.001) in the group that qualified for acyclovir. We conclude that acyclovir provides incomplete protection from the negative impact of CMV on graft survival. [ABSTRACT FROM AUTHOR]

Graft survival in the autosomal dominant polycystic kidney disease (ADPKD) transplant population at our center was compared to other end stage renal disease (ESRD) transplant recipients (excluding diabetics). There were 1512 adult cadaveric renal transplants carried out at our center between 1989 and 2002. After exclusions, 1372 renal grafts were included in the study. Using Kaplan-Meier methods, patient and graft survival were determined and compared between the two groups. Mean age at transplant was significantly older for the ADPKD group of patients. The age adjusted graft survival at 5 years was 79% for ADPKD patients compared to 68% in the controls. Patient survival for ADPKD patients improved from 89% at 5 years to 95% when age adjusted. Using the Cox proportional hazards models to compare ADPKD with other causes of ESRD (including recipient age and other variables) in a multifactorial model, ADPKD was significant at the 5% level ( p = 0.036). This study demonstrates a graft and patient survival advantage in ADPKD patients when age-matched compared to other ESRD patients. [ABSTRACT FROM AUTHOR]

Background: Acute renal failure (ARF) is a frequent complication of coronary artery bypass grafting (CABG) surgery and is strongly associated with perioperative morbidity and mortality. We hypothesized that renal artery stenosis (RAS), causing occult renal ischemia, may be an important factor contributing to development of ARF after CABG surgery. Methods: Preoperative and intraoperative data on 798 consecutive adult patients undergoing CABG surgery with cardiopulmonary bypass from February 1, 1995 to February 1, 1997 (who had also undergone an abdominal aortogram for the evaluation of RAS) were recorded and entered into a computerized database. The development of ARF was defined as a rise in serum creatinine of 1 mg/dL (88.4 µmol/L) above baseline postoperatively. The association between the presence of renal artery stenosis together with preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. Results: A total of 798 patients underwent isolated coronary bypass grafting, of which 18.7% demonstrated 50% or more RAS. ARF developed in 82 patients (10.2%), of which three (0.3%) required dialysis support. The mortality for patients who developed ARF was 14% (OR 15, P'=0.0001) compared to 0.2% among those who did not develop ARF. The presence of renal artery stenosis of any severity ranging from unilateral 50% RAS to bilateral 95% RAS was not associated with the subsequent development of ARF. Conclusions: The development of ARF following CABG surgery is associated with high mortality. The presence of RAS does not appear to increase the risk for developing ARF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Since the earliest reports of the use of Epoetin alfa in hemodialysis patients, it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease (ESRD) patients not previously hypertensive. We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30 ± 3% to 42 ± 3% with the use of Epoetin alfa would result in increased blood pressure. This study was a substudy of the “Normal hematocrit Study”. MethodsThirty-one patients were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42 ± 3% and patients in Group B were maintained with a hematocrit of 30 ± 3% throughout the course of the study. All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following randomization when they had achieved their target hematocrit. Pre-dialysis systolic and diastolic BP was also recorded. ResultsThe mean hematocrit increased in Group A from 29.1 ± 2.4% to 40.8 ± 5.2% after 30 weeks. The hematocrit in Group B remained stable at 30 ± 3% throughout the course of the study. There was no difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up. Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study. ConclusionIt is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa. The increase in hematocrit from 30 ± 3% to 42 ± 3% is not associated with increased blood pressure. [ABSTRACT FROM AUTHOR]