Patrick O’Kelly

C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome

BACKGROUND AND OBJECTIVES The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. RESULTS Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. CONCLUSIONS Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression

Aims:  To investigate the expression of matrix metalloproteinase (MMP)‐2, MMP‐9, and tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 in non‐melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors.

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.

Renal allograft loss in the first post‐operative month: causes and consequences

Phelan PJ, O’Kelly P, Tarazi M, Tarazi N, Salehmohamed MR, Little DM, Magee C, Conlon PJ. Renal allograft loss in the first post‐operative month: causes and consequences.

Analysis of waiting times on Irish renal transplant list

Phelan PJ, O’Kelly P, O’Neill D, Little D, Hickey D, Keogan M, Walshe J, Magee C, Conlon PJ. Analysis of waiting times on Irish renal transplant list.
Clin Transplant 2010: 24: 381–385.

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.

An assessment of the long-term health outcome of renal transplant recipients in Ireland

BackgroundRenal transplantation remains the preferred method of renal replacement therapy in terms of patient survival, quality of life and cost. However, patients have a high risk of complications ranging from rejection episodes, infection and cancer, amongst others.Aims and methodsIn this study, we sought to determine the long-term health outcomes and preventive health measures undertaken for the 1,536 living renal transplant patients in Ireland using a self-reported questionnaire. Outcomes were divided into categories, namely, general health information, allograft-related information, immunosuppression-related complications and preventive health measures.ResultsThe results demonstrate a high rate of cardiovascular, neoplastic and infectious complications in our transplant patients. Moreover, preventive health measures are often not undertaken by patients and lifestyle choices can be poor.ConclusionsThis study highlights the work needed by the transplantation community to improve patient education, adjust immunosuppression where necessary and aggressively manage patient risk factors.

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

AbstractBackground 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. Aim To examine the outcome of renal transplantation in patients with hepatitis C. Methods 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. Results 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. Conclusion 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.

Outcomes of Renal Transplantation in Patients With Bipolar Affective Disorder and Schizophrenia: A National Retrospective Cohort Study

BACKGROUND Patients with severe psychiatric disorders such as schizophrenia and bipolar affective disorder (BPAD) have in the past been excluded from organ transplantation programs based on their psychiatric illness. However, there is little data on the outcomes of renal transplantation in these patients and little evidence to support such exclusion. METHODS We reviewed the database of the Irish National Renal Transplant Programme and identified all patients with a history of BPAD or schizophrenia who had received a transplant over a 28-year period. Data were collected for the following outcomes: patient survival, graft survival, graft function, length of hospitalization for transplantation, and frequency of acute rejection episodes. The control group was the general transplant group, that is, all patients without these psychiatric disorders and who had received a renal transplant during the relevant time period. RESULTS Between January 1, 1986, and December 31, 2013, 3000 renal transplants were performed at our center. Of the transplant recipients, 0.5% (n = 15) had a diagnosis of BPAD and 0.2% (n = 6) had schizophrenia. No significant differences were found between the BPAD or schizophrenia group and the general renal transplant group in relation to patient survival, graft survival, and graft function. In addition, length of hospital admission for transplantation and frequency of acute rejection episodes were comparable among the 3 groups. CONCLUSIONS Although consideration of psychiatric comorbidity is an important part of pretransplant assessment and selection, patients should not be discriminated against based on a diagnosis of BPAD or schizophrenia as there is no evidence that this negatively affects transplant outcomes.

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.