Trends in adult post-kidney transplant immunosuppressive use in Australia, 1991-2005

Aim: Kidney transplant outcomes have improved over the past 15 years, partly due to improvements in immunosuppression. We used data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry to examine trends in immunosuppressive use post transplant. Methods: All adult (recipient age 16+ years) kidney‐only transplants performed in Australia from April 1991 to December 2005 were followed to graft loss or December 2005. Immunosuppressive use at induction, 1, 3 and 5 years post transplant were analysed by transplant cohort. Results: Calcineurin‐inhibitors (CNI) were used in most recipients for induction and maintenance immunosuppression, with increasing tacrolimus use. Induction cyclosporin dose increased since 2001 (from 5.8 to 7.9 mg/kg per day), but maintenance cyclosporin and tacrolimus dose decreased (from 3.8 to 3.0 mg/kg per day cyclosporin at 1 year post transplant). CNI‐free induction increased since 2002 (from 1.4% to 8.4%), while CNI‐free maintenance increased throughout the study period. Mycophenolates were the predominant antimetabolite used. Steroid‐free maintenance decreased (from 22.7% to 8.7% at 1 year post transplant), as did median prednisolone doses (from 0.12 to 0.09 mg/kg per day at 1 year post transplant). Sirolimus or everolimus are increasingly used for CNI‐sparing rather than as antimetabolites substitutes. OKT3 or antithymocyte globulin induction decreased, while anti‐CD25 antibody usage increased from 9.5% to 57.1% since 2000. Conclusion: There is a trend to more potent induction immunosuppression with tacrolimus, mycophenolates and anti‐CD‐25 antibodies, but with CNI avoidance or minimization during maintenance phase. While steroid avoidance/cessation decreased, maintenance steroid dose has also decreased. Anti‐CD25 antibodies are now used in >50% of recipients.     

Trends in Incidence of ESKD in People With Type 1 and Type 2 Diabetes in Australia, 2002-2013

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Interleukin‐2 receptor antibody does not reduce rejection risk in low immunological risk or tacrolimus‐treated intermediate immunological risk renal transplant recipients

Aim: The use of interleukin‐2 receptor antibody (IL‐2Ra) induction has been associated with reduced rejection rates in renal transplant recipients. However, the effect of IL‐2Ra induction on graft and patient outcomes in renal transplant recipients with differing immunological risk remains unclear. Methods: Using Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients in Australia between 1995 and 2005 were included. Recipients were stratified into low immunological risk (primary grafts with ≤2 human leucocyte antigen (HLA)‐mismatches and panel‐reactive antibody (PRA) < 10%) or intermediate immunological risk (subsequent grafts or >2 HLA‐mismatches or PRA > 25%) recipients. Recipients receiving T‐cell depletive induction therapy or steroid and/or calcineurin‐free inhibitor regimens were excluded. Outcomes analysed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 5 years, graft and patient survival. Results: 218 of 1220 (18%) low‐risk and 883 of 3204 (28%) intermediate‐risk recipients received IL‐2Ra. In intermediate‐risk recipients, IL‐2Ra induction was associated with a 26% reduction in the incidence of acute rejection; but this benefit was restricted only to recipients initiated on cyclosporine‐based immunosuppressive regimens. In contrast, the use of IL‐2Ra in low‐risk recipients was not associated with reduced rejection risk. There was no association between IL‐2Ra induction and other graft or patient outcomes in both low‐ and intermediate‐risk recipients. Conclusion: This registry analysis suggests that IL‐2Ra induction may be associated with a reduction in rejection risk in cyclosporine‐treated intermediate immunological risk recipients, but not in low‐risk renal transplant recipients.     

Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients

Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys. The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable. Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined. The association between the number of HLA mismatches and HLA-loci mismatches and outcomes were examined. Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches. Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models. HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants. Increasing HLA-AB and HLA-DR mismatches were associated with a greater risk of acute rejection, graft failure, death-censored graft failure, and/or death. There was no consistent association between initial immunosuppressive regimen and outcomes. Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era.     

A review of utility-based allocation strategies to maximize graft years of deceased donor kidneys

With the continuing shortage of deceased donor kidneys coupled with a growing number of older potential recipients, there has been a greater acceptance of using older donor kidneys, including increased utility of expanded criteria donor (ECD) kidneys. In this review, we will look at the impact of using ECD kidneys on graft and patient survival, and to identify modifiable factors that may improve transplant outcomes in recipients receiving ECD kidneys. In addition, we will discuss whether the implementation of utility-based allocation strategies to maximize graft outcomes is an appropriate way forward to provide a better balance between utility and equity in the distribution of deceased donor kidneys.     

Atrial fibrillation in haemodialysis patients: Do the guidelines for anticoagulation apply?

AIM: Atrial fibrillation (AF) is common in haemodialysis patients, but the risks and benefits of anticoagulation in this group are not well characterized. We investigated the prevalence of AF, its associated risk factors, and the incidence of stroke and haemorrhage in a cohort of haemodialysis patients. METHODS: We retrospectively reviewed 155 patients undergoing maintenance haemodialysis on 1 April 2003 (age 56.9 +/- 13.5 years; men 62.6%; mean duration of haemodialysis 39.3 +/- 37.5 months). Patients with paroxysmal or permanent AF were identified, and baseline clinical and echocardiographic data were obtained. The incidence of cerebrovascular accidents, major haemorrhage and all-cause mortality was assessed during the 26 month average follow-up period. RESULTS: AF was present in 25.8% of patients, paroxysmal in 18.1%, and permanent in 7.7%. Patients with AF were more likely to be older (64.2 +/- 9.4 vs 54.4 +/- 13.8 years; P < 0.005), have underlying ischaemic heart disease or congestive heart failure, and have a lower serum albumin (P < 0.05 for all). Only 12.5% of AF patients were anticoagulated, although 47.5% had contraindications to warfarin. Cerebrovascular events occurred in 5.2% of all patients (30.4 episodes/1000 patient-years), and major haemorrhage in 20.0% (106.4 episodes/1000 patient-years). All-cause mortality was 29.7%. The endpoints for the AF group did not significantly differ from the non-AF group. CONCLUSION: AF is common in haemodialysis patients. The incidence of major haemorrhage was over three times that of cerebrovascular accidents. Guideline recommendations for anticoagulation in AF in the general population may not be appropriate for the haemodialysis population.     

Severe vesicoureteral reflux and chronic renal failure: a condition peculiar to male gender? Data from the ItalKid Project

Primary vesicoureteral reflux (VUR), one of the principal causes of chronic renal failure (CRF), occurs as a result of two distinct and sex-related mechanisms: congenital renal hypoplasia, which is prevalent in males, and acquired renal scarring in females. We used data from the ItalKid Project, a prospective population-based CRF registry of patients undergoing conservative treatment, to evaluate the gender distribution and severity of primary VUR, the age at diagnosis, and the diagnostic and therapeutic methods adopted in children with CRF. The prevalence of males (77.5%), the severity of VUR (grade IV-V), and the early age at diagnosis (18% prenatally) seem to suggest that congenital renal damage is the major cause of pediatric CRF.