Mark Denton

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.

Arterio-venous fistula buttonhole cannulation technique: a retrospective analysis of infectious complications

Background There are two main methods of accessing arterio-venous fistulas (AVFs); the ‘buttonhole’ and the ‘rope-ladder’ cannulation technique. Several small studies have hypothesized that the buttonhole technique is associated with increased rates of fistula-associated infection. This study addresses this hypothesis. Methods A retrospective review of all patients attending a large outpatient haemodialysis clinic was performed. Data were collected on the method of cannulation, infection rates, implicated microorganisms, complications of infection and time on haemodialysis. Results A total of 127 patients had received haemodialysis via an AVF: 53 via the rope-ladder technique and 74 via the buttonhole technique. Nine episodes of clinically significant bacteraemia were recorded in the buttonhole group. This equated to a rate of 0.073 bacteraemia events per 1000 AVF days. There were no episodes of bacteraemia in the rope-ladder group. Eight infections were due to methicillin-sensitive Staphylococcus aureus (MSSA); one was due to Staphylococcus epidermidis. Three patients with MSSA bacteraemia subsequently developed infective endocarditis. Five patients who developed bacteraemia events had been undergoing home haemodialysis. Conclusions This study highlights the infectious complications associated with buttonhole cannulation techniques. All organisms isolated in our cohort were known skin colonizers. The reason for the increased rates of infection is unclear. Given this high rate of often life-threatening infection, we recommend regular audit of infection rates. We currently do not recommend this technique to our patients receiving haemodialysis.

Clinical and pathologic characteristics of hereditary apolipoprotein A-I amyloidosis in Ireland.

Apolipoprotein A‐I amyloidosis is a rare, autosomal dominant disorder characterized by progressive accumulation of amyloid fibrils in tissues, leading to renal and hepatic disease. We describe the clinical manifestations and pathologic features of kidney disease in three Irish families.

Dialysis-dependent renal failure at diagnosis continues to be associated with very poor outcome in multiple myeloma.

Chang, W.J., Kim, S.J. & Kim, K. (2014) Central nervous system myeloma : a different cytogenetic profile? British Journal of Haematology, 164, 745–748. Gozzetti, A., Cerase, A., Lotti, F., Rossi, D., Palumbo, A., Petrucci, M.T., Patriarca, F., Nozzoli, C., Cavo, M., Offidani, M., Floridia, M., Berretta, S., Vallone, R., Musto, P., Lauria, F. & GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) Myeloma Working Party (2012) Extramedullary intracranial localizations of multiple myeloma and treatment with novel agents: a retrospective survey of 50 patients. Cancer, 118, 1574–1584.

Concordance of outcomes of pairs of kidneys transplanted into different recipients

Kidney transplant outcomes are influenced by donor characteristics, including age and gender. Additional donor factors, both genetic and environmental, also influence graft outcome. We aim to assess the strength of donor factors in determining kidney transplant outcomes by comparing paired kidneys from a single donor transplanted into different recipients. We conducted a retrospective cohort study of outcomes of pairs of deceased donor kidneys transplanted in our centre between 1992 and 2008. We examined the relationship within pairs for eGFR at 1 year and at 5 years post‐transplant using Spearman’s Correlation and the concordance of pairs of transplant kidneys with respect to the occurrence of acute rejection and delayed graft function (DGF). A total of 652 recipient pairs were analysed. Spearman’s correlation for eGFR was 0.36 at 1 year and 0.36 at 5 years post‐transplant. The incidence of DGF was 11%. The odds ratio of DGF occurring if the contralateral kidney had DGF was 5.99 (95% CI, 3.19–11.25). There is a significant degree of relationship within pairs of kidneys transplanted from the same donor for serum creatinine at 1 year and 5 years post‐transplant and also for the occurrence of delayed graft function.

The Irish living kidney donor program - why potential donors do not proceed to live kidney donation?

Living donation is not only a method to increase access to kidney transplantation but can also offer superior outcomes. We report the experience of the living donor (LD) program in the Republic of Ireland and explore reasons why potential donors do not proceed to live donation.

Home haemodialysis in Ireland.

BackgroundA home haemodialysis programme (HHD) was established in Ireland in 2009 following studies suggesting better outcomes and a survival advantage when compared to conventional in-centre dialysis.AimThe aim of this study was to assess the outcomes in patients commenced on the HHD programme.MethodsBaseline characteristics, standard dialysis parameters, blood pressure control, antihypertensive usage, vascular access problems, hospitalisation rates and technical issues related to dialysis were analysed.ResultsSeventeen patients were followed over a 2-year period. Time spent travelling for dialysis-related treatments was reduced with time on dialysis per week increased. There was a trend towards lower blood pressure with nine patients, either discontinuing or having a reduction in antihypertensive medications. There were eight episodes of hospitalisation with the majority of complications related to vascular access.ConclusionHome haemodialysis is a community-based therapy, offering an alternative to conventional in-centre haemodialysis in a select patient population.

Glomerular disease recurrence in second and subsequent kidney transplants.

INTRODUCTION Primary glomerular diseases such as primary focal segmental glomerular sclerosis (FSGS), IgA Nephropathy and membrano-proliferative glomerulonephritis (MPGN) may recur in renal transplants, and can potentially lead to graft failure. The rate of recurrence in second and subsequent renal transplants, following failure of the first graft due to recurrence, is unclear. METHODS A retrospective review of the Irish transplant database from 1982 to 2009 was performed. Patients were included for analysis if their first graft failed due to biopsy-confirmed recurrent glomerular disease (primary FSGS, IgA nephropathy or MPGN) and they underwent subsequent re-transplantation. RESULTS 3,330 deceased and living renal transplants were performed during the time period in question. 33 patients had a deceased donor renal transplant following recurrence of primary FSGS, IgA nephropathy or MPGN causing first graft failure. Clinically significant disease recurrence was seen in 44% of re-transplants at 10 years. Median second graft survival in this group was 9.1 years. The median graft survival was 10.5 years for all other re-transplants performed in Ireland during the same time period. CONCLUSION Clinically significant disease recurrence does not necessarily affect re-transplants following loss of the first graft to disease recurrence. Selected patients who experience first graft failure due to recurrent glomerular disease should not be precluded from receiving a second transplant.

Factors affecting eGFR 5-year post-deceased donor renal transplant: analysis and predictive model

Abstract 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.

Recurrent and De Novo Glomerulonephritis After Kidney Transplantation

Glomerulonephritis is the primary disease in over a third of patients undergoing renal transplantation. All forms of glomerulonephritis may recur histologically in the renal allograft, but the incidence and severity of clinical recurrence vary greatly according to the type of glomerular disease. Recurrence may be early post-transplant or may take many years. Glomerular diseases that recur late will increase in clinical significance as advances in immunosuppression reduce rejection-mediated graft loss and prolong transplant survival. Registry data shows that the risk of graft loss from recurrence increases with the number of follow-up years, from 0.6% at the first postoperative year to 8.4% at 10 years. Recurrence was the third most frequent cause of allograft loss at 10 years, after chronic allograft failure and death with a functioning allograft. Interestingly, the use of more potent maintenance immunosuppressive agents or more potent induction agents such as alemtuzumab do not appear to reduce recurrence rates. De novo glomerulonephritis may also occur in renal transplants. This chapter reviews the incidence, clinical features, treatment, and impact on renal transplant survival of the major forms of de novo and recurrent glomerular disease.