Search

Introduction: Coronary artery disease (CAD) accounts for half of all deaths in patients with end stage kidney disease (ESKD) after renal transplantation. In these patients, 'angiographically' significant CAD may be asymptomatic. Identification of these patients, with subsequent revascularisation, may reduce adverse cardiovascular events in the peritransplant and post-transplant periods. Objective(s): We aimed to evaluate the effectiveness of diagnostic (>=85% maximum age-predicted heart rate) dobutamine stress cardiac magnetic resonance (DSCMR) imaging in identifying 'angiographically' significant CAD in asymptomatic renal transplant candidates. Method(s): Over a five year period, 62 asymptomatic, high-risk patients with ESKD were referred to this program by their nephrologists as part of pre-renal transplant assessment. All had at least one traditional cardiovascular risk factor. 58 (94%) were on renal replacement therapy. Of the 62 enrolled patients, 43 (69%) had both a diagnostic DSCMR and an invasive coronary angiogram (ICA). DSCMR reporters were blinded to results of ICA and vice-versa. 19 patients (31%) were excluded from the analysis due to non-diagnostic DSCMR scans, with the most common reasons being insufficient augmentation in heart rate with dobutamine stress (in 8 patients) and claustrophobia (in 5 patients). Significant CAD was defined on ICA as a coronary stenosis of >= 70%. Result(s): Of the 43 included patients, 12 (28%) had significant CAD, and all had evidence of inducible myocardial ischaemia on DSCMR. 3 (7.0%) patients had false positive DSCMR scans. There were no false negative scans. Of the 19 patients with non-diagnostic DSCMR scans, 7 (37%) subjects had significant CAD. In this cohort studied with a diagnostic DSCMR: sensitivity = 100%, specificity = 90%, positive predictive value = 80%, negative predictive value = 100%. 26 patients have undergone successful transplantation and 8 patients have died, all without transplantation). Conclusion(s

Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine. Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the seven-year risk of incident cancer and other graft outcomes among a subgroup of recipients who had participated in the A2309 study using adjusted Cox proportional hazard models. Of 95 recipients, 66 were randomized to everolimus (1.5 mg or 3 mg) with reduced cyclosporine and 29 received mycophenolate sodium and standard exposure cyclosporine. Compared to mycophenolate sodium and standard exposure cyclosporine, everolimus treatment was associated with unadjusted hazard ratios of 0.28 (95% confidence interval 0.11-0.74), 0.39 (0.16-0.98) and 0.41 (0.23-0.71), respectively for nonmelanoma skin cancer, non-skin cancers and any cancers. Interestingly, the adjusted hazard ratios were 0.34 (0.13-0.91), 0.35 (0.09-1.25) and 0.32 (0.15-0.71), respectively. There was no association between treatment groups and rejection, graft loss or death. Compared to standard-exposure cyclosporine, everolimus with reduced exposure to cyclosporine may be associated with a reduced risk of cancer, particularly for non-melanoma skin cancer. Thus, if confirmed in larger patient cohorts, de novo use of everolimus with reduced exposure to calcineurin inhibitors may enable a reduction in cancer burden after transplantation.Copyright © 2017 International Society of Nephrology

This was a systematic review of randomized controlled trials comparing delayed conversion of mammalian target of rapamycin inhibitors (mTORi) for calcineurin inhibitors (CNIs) versus CNI continuation in kidney transplantation. Databases (2000-2012) and conference abstracts (2009-2012) were searched giving a total of 29 trials. Outcomes analyzed included GFR, graft loss, rejection and adverse events and were expressed as weighted mean differences (WMDs) or as risk ratios (RRs). Patients converted to mTORi up to 1 year posttransplant in intention-to-treat analysis had higher GFR compared with those remaining on CNI (WMD 0.28 mL/min/1.73 m2, 95% confidence interval [CI] 0.21-0.36; I2 = 68%, p < 0.001). Stratifying trials by time posttransplant or type of mTORi did not change the overall heterogeneity. For on-treatment population, mTORi was associated with higher GFR (14.21 mL/min/1.73 m 2, 10.34-18.08; I2 = 0%, p = 0.970) 2-5 years posttransplant. The risk of rejection at 1 year was higher in mTORi trials (RR 1.72, 1.34-2.22; I2 = 12%, p = 0.330). Discontinuation secondary to adverse events was more common in patients on mTORi, whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi. Conversion from CNI to mTORi is associated with short-term improvements in GFR in a number of studies but longer-term follow-up data of graft and patient survival are required. This systematic review shows that conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitor after kidney transplantation is associated with short-term improvement in graft function despite a higher risk of early rejection. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Background: Coronary artery disease (CAD) accounts for half of all deaths in patients with end stage kidney disease (ESKD) who have undergone renal transplantation. In patients with ESKD, "angiographically" significant CAD may be asymptomatic. Identification of these patients, with subsequent revascularisation, may reduce the prevalence of adverse cardiovascular events in the peri-transplant and post-transplant period. We aimed to evaluate the effectiveness of diagnostic (>85% maximum age-predicted heart rate) dobutamine stress cardiac magnetic resonance (DSCMR) imaging in identifying "angiographically" significant CAD in asymptomatic patients. Method(s): Over a five year period, 62 high-risk patients were referred to this program by the nephrology team. All of these subjects had an invasive coronary angiogram (ICA). These subjects had ESKD and were being considered for renal transplantation. 42 (68%) were male. All had at least one traditional cardiovascular risk factor. 58 (94%) were on renal replacement therapy. Of the 62 enrolled patients, 43 (69%) had a diagnostic DSCMR followed by an ICA. ICA reporters were blinded to results of DSCMR and viceversa. 19 patients (31%) were excluded from the analysis due to nondiagnostic DSCMR scans. The most common reasons for a nondiagnostic DSCMR included insufficient augmentation in heart rate with dobutamine stress (in 8 patients) and claustrophobia (in 5 patients). Significant CAD was defined on ICA as a coronary stenosis of >= 70%. Result(s): Of the 43 included patients, 12 (28%) had significant CAD, and all of these patients had evidence of inducible myocardial ischaemia on DSCMR. 3 (7.0%) patients had false positive DSCMR scans. There were no false negative scans. Of the 19 patients with non-diagnostic CMR scans, 7 patients had significant CAD on ICA. In this cohort studied with a diagnostic DSCMR: sensitivity = 100%, specificity = 90%, positive predictive value = 80%, negative predictive value = 100%. Over this period

Introduction: A collaborative group of eight Transplant Units in Australia defined a protocol for ABOi kidney transplants in an attempt to standardise therapy and collect prospective data. Method(s): Forty-two ABOi transplants were performed. Blood group titres were predominantly measured by gelcard (alternative method used in 5 cases) and the protocol allowed for Glycorex columns or plasma-exchange to reduce titres to <1:8. All but 2 recipients received Rituximab pre-transplantation, all commenced Mycophenolate and received IVIG 0.5g/kg pre transplant, with Tacrolimus based maintenance immunosuppression. Result(s): Baseline ABO titres ranged from 1:1024 to 1:1. At median follow-up of 14 months (range 1-36), patient survival was 95%, death censored graft survival was 93% and median creatinine was 121umol/l (range 82-175). There were 4 episodes of cellular rejection plus 4 cases of antibody mediated rejection (AbMR), one of which caused graft loss. One graft was lost to chronic transplant glomerulopathy and one to thrombosis, neither of these were thought to relate to ABOi AbMR. There were two deaths from pulmonary Aspergillosis, in males aged 67 and 73 at month 2 and 3 respectively. Other significant complications included haemorrhage requiring transfusion, BK nephropathy (n=2), Mycobacterium haemophilum cellulitis and pulmonary Cryptococcus and Streptococcus pneumonia. Conclusion(s): Our uncontrolled series of ABOi transplants was associated with an increased incidence of graft loss and serious infections compared to routine kidney transplantation. Components of the protocol may be implicated in some of these outcomes which highlights the need for controlled data.

We report 6-month results of renal allograft recipients enrolled in seven Australian centers as part of a worldwide, multicenter, randomized, open-label, concentration-controlled trial comparing standard tacrolimus (sTAC) with reduced tacrolimus (rTAC) both with sirolimus (SRL) and steroids. Patients were randomized 1:1 to either rTAC (n = 33) with a target maintenance concentration of SRL of 8 to 15 ng/mL and TAC of 3 to 7 ng/mL, or sTAC (n = 31) with SRL target of 5 to 10 ng/mL and TAC of 8 to 12 ng/mL. Antibody induction was prohibited. Adult recipients of a first or second cadaveric or non-HLA-identical living donor renal graft were eligible for enrollment. Recipients with a panel-reactive antibody level of >50% and recipients of regrafts who had lost their first graft from rejection within the first 6 months were ineligible. The groups were compared for graft function, incidence of rejection, and patient and graft survival at 6 months. There were no differences in demographics. There were 30% and 29% discontinuations in the rTAC and sTAC groups mainly due to adverse events in the first month. The 6-month patient and graft survival by intention-to-treat analysis was 94% and 91% for rTAC and 100% and 97% for sTAC (P = NS), respectively. Incidence and severity of biopsy-proven acute rejection was not different between the two groups, being 21% for rTAC and 19% for sTAC. The mean serum creatinine was 121 mumol/L and 148 mumol/L for rTAC and sTAC groups (P = .09), respectively. Glomerular filtration rate (GFR) was 68 mL/min and 62 mL/min (P = .23), respectively. Adverse events, infections, and antihypertensive and antilipidemic agent usage were similar. Of interest is that the overall incidence of thrombotic microangiopathy was 14%. These results support the safety and efficacy of SRL + TAC. Reduced TAC is associated with a trend toward improved renal function.

The association between pretransplant dialysis modality and transplant outcomes remains inconsistent. The aim of this study is to address the association between alteration in dialysis modality and post-transplant outcomes. Using Australia and New Zealand Dialysis and Transplant Registry, primary live- and deceased-donor renal transplant recipients (RTR) between 1997 and 2009 were examined. Pre-emptive and multiple-organ transplants were excluded. The association between initial and pretransplant dialysis modality and transplant outcomes were examined. Of the 6701 RTR, 18.6% were initiated-maintained on peritoneal dialysis pretransplant (PD-PD), 9.2% were initiated on PD, but maintained on haemodialysis (HD) pretransplant (PD-HD), 63.3% were HD-HD and 8.9% were HD-PD. PD-HD [odds ratio(OR)1.44, 95% CI 1.21,1.72] and HD-HD (OR1.25, 95% CI 1.12,1.41) were associated with a significantly greater risk of slow graft function compared with the overall mean of the groups, whereas a change in initial dialysis modality from HD to pretransplant PD was associated with higher risk of overall graft failure [hazard ratio(HR)1.19, 95% CI 1.04,1.36) and recipient death (HR1.34, 95% CI 1.13,1.59). Our registry analysis suggest that dialysis modality pretransplant may affect transplant outcomes and future studies evaluating patient selection, choice of modality and/or potential interventions in the pre and post-transplant period may have a beneficial effect on post-transplant outcomes. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

The latest Caring for Australians with Renal Impairment (CARI) guideline detailing renal transplant care, developed as a local modification of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. © 2011 Asian Pacific Society of Nephrology.

Background: Recurrent glomerulonephritis is a known cause of renal allograft loss; however, the incidence of this complication is poorly defined. We determined the incidence, timing, and relative importance of allograft loss due to the recurrence of glomerulonephritis. Method(s): A total of 1505 patients with biopsy-proved glomerulonephritis received a primary renal transplant in Australia from 1988 through 1997. Recurrence was confirmed by renal biopsy. The Kaplan-Meier method was used to estimate the 10-year incidence of allograft failure due to recurrent glomerulonephritis, and this incidence was compared with the incidence of acute rejection, chronic rejection, and death with a functioning allograft. Characteristics of the recipients and donors were examined as potential predictors of recurrence. Result(s): Allograft loss due to the recurrence of glomerulonephritis occurred in 52 recipients, with a 10-year incidence of 8.4 percent (95 percent confidence interval, 5.9 to 12.0). The type of glomerulonephritis, the sex of the recipient, and the peak level of panel reactive antibodies were independent predictors of the risk of recurrence. Recurrence was the third most frequent cause of allograft loss at 10 years, after chronic rejection and death with a functioning allograft. Despite the effect of recurrence, the overall 10-year incidence of allograft loss was similar among transplant recipients with biopsy-proved glomerulonephritis and among those with other causes of renal failure (45.4 percent [95 percent confidence interval, 40.9 to 50.2] vs. 45.8 percent [95 percent confidence interval, 42.3 to 49.3], 49.31, P=0.09). Conclusion(s): Recurrence is an important cause of allograft loss for those with renal failure due to glomerulonephritis. No risk factors for recurrence were identified that warrant altering the approach to transplantation. However, accurate estimates of risk can now be provided to potential recipients of renal allografts. Copyright © 2002 Massachu