Search

Pre-emptive kidney transplantation is the recommended strategy for patients with end-stage renal failure in all guidelines [Kidney Disease: Improving Global Outcomes (KDIGO), The Australian and New Zealand Dialysis and Transplantation Registry (ANZDATA), European Renal Best Practice Guideline (ERBP), British Transplant Society (BTS)]. This recommendation is intuitive and based on few older studies with considerable limitations. In addition, there is conflicting evidence as to whether the duration of dialysis vintage impacts on graft and patient survival after transplantation. The objective of this structured review was to critically review the published evidence on dialysis vintage and outcomes by including the most recent papers on that topic. We searched Medline using keywords for kidney transplantation, pre-emptive, dialysis vintage and relevant outcomes, and found 14 eligible cohort studies. The best evidence was found for pre-emptive transplantation, which was found to be associated with a lower risk of actual graft loss (including death as event) compared with non-pre-emptive transplantation. When only patients were considered that have been registered pre-emptively but then received or did not receive a pre-emptive transplant, the association with functional graft survival (excluding death as event) was only marginal. Dialysis vintage had a graded association with patient survival in most of the studies, but an unclear estimate with functional graft survival. Older studies also found an association of dialysis vintage with death-censored graft survival, but this association is likely confounded by selection and the competing risk of death and was no longer observed in recent eras, i.e. in transplants performed in the last decade. In summary, the recommendation for pre-emptive kidney transplantation for optimal patient and graft survival remains valid even in recent periods but the association of dialysis vintage after dialysis initiation with death-censored graft survival is less clear. The association of dialysis vintage with mortality after transplantation depends on the median duration of dialysis of the wait-listed population as well as acceptance rates for transplantation, and may thus be country specific. Nevertheless, it is reasonable to advocate pre-emptive kidney transplantation in all age groups. What remains unsolved is the selection issues since the reasons for longer waiting time on dialysis are difficult to capture in retrospective observational studies, and lead time as well as immortal time bias may have confounded the mortality data. [ABSTRACT FROM AUTHOR]

Background Mycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure. Methods A multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 ('IMPACT' study). Results Of the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20–132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0–65.9) mg*h/L versus pantoprazole: 43.8 (35.6–53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5–49.2) mg*h/L versus pantoprazole: 45.9 (35.5–59.3) mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group. Conclusions The co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations. [ABSTRACT FROM AUTHOR]

Background Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death. Methods This study included new adult PD patients in Australia and New Zealand (ANZ; 1990–2010) or Scotland (2000–08) followed until 2012. Age, time on PD, primary renal disease, gender, data set and diabetic status were evaluated as predictors at the start of PD, then at 3 and 5 years after starting PD using flexible parametric competing risks models. Results In 17 396 patients (16 162 ANZ, 1234 Scotland), EPS was observed in 99 (0.57%) patients, less frequently in ANZ patients (n  = 65; 0.4%) than in Scottish patients (n  = 34; 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1 Kaplan–Meier = 0.0126, cumulative incidence function = 0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74–0.79) and this improved at 3 and 5 years after starting PD (C-statistic = 0.81–0.92). Conclusions EPS risk estimates are lower when calculated using competing risk of death analyses. A patient's estimated risk of EPS is country-specific and can be predicted using age, primary renal disease and duration of PD. [ABSTRACT FROM AUTHOR]

Background A number of peritoneal dialysis (PD) systems are available but there have been few studies comparing them. The aim of this study was to examine technique failure and patient survival between different PD company systems. Methods The study included all patients who commenced PD between 1995 and 2014 in Australia and New Zealand. Groups were compared according to the initial PD company system that they received. The primary outcome was a composite of PD technique failure and death. Results A total of 16 575 patients commenced PD using systems manufactured by Baxter [ n  = 13 438 (81%)], Fresenius Medical Care [ n  = 2848 (17%)] or Gambro [ n  = 289 (2%)]. Of these, 11 870 (72%) developed technique failure, including 5421 (33%) who died. The median time to technique failure or death for all patients was 625 [interquartile range (IQR) 318–1114] days: 629.5 (IQR 321–1121) days with Baxter, 620.5 (IQR 311–1069) days with Fresenius Medical Care and 538 (IQR 272–1001) days with Gambro systems (P = 0.023). There was a statistically significant increase in technique failure or mortality rates in patients on Gambro {adjusted incidence rate ratio [IRR] 1.46 [95% confidence interval (CI) 1.33–1.62]} and Fresenius [adjusted IRR 1.10 (95% CI 1.01–1.19)] systems compared with Baxter systems. No difference in patient survival was observed between the three PD systems. Conclusions PD systems manufactured by different companies may be associated with important differences in PD technique survival. This needs to be confirmed with adequately powered, prospective randomized controlled clinical trials. [ABSTRACT FROM AUTHOR]

Background It is unclear if haemodiafiltration improves patient survival compared with standard haemodialysis. Observational studies have tended to show benefit with haemodiafiltration, while meta-analyses have not provided definitive proof of superiority. Methods Using data from the Australia and New Zealand Dialysis and Transplant Registry, this binational inception cohort study compared all adult patients who commenced haemodialysis in Australia and New Zealand between 2000 and 2014. The primary outcome was all-cause mortality. Cardiovascular mortality was the secondary outcome. Outcomes were measured from the first haemodialysis treatment and were examined using multivariable Cox regression analyses. Patients were censored at permanent discontinuation of haemodialysis or at 31 December 2014. Analyses were stratified by country. Results The study included 26 961 patients (4110 haemodiafiltration, 22 851 standard haemodialysis; 22 774 Australia, 4187 New Zealand) with a median follow-up of 5.31 (interquartile range 2.87–8.36) years. Median age was 62 years, 61% were male, 71% were Caucasian. Compared with standard haemodialysis, haemodiafiltration was associated with a significantly lower risk of all-cause mortality [adjusted hazard ratio (HR) for Australia 0.79, 95% confidence interval (95% CI) 0.72–0.87; adjusted HR for New Zealand 0.88, 95% CI 0.78–1.00]. In Australian patients, there was also an association between haemodiafiltration and reduced cardiovascular mortality (adjusted HR 0.78, 95% CI 0.64–0.95). Conclusion Haemodiafiltration was associated with superior survival across patient subgroups of age, sex and comorbidity. [ABSTRACT FROM AUTHOR]

Background. Donor and recipient age in kidney transplantation are known to affect graft and patient survival. In deceased- donor (DD) transplantation, donor and recipient age matching are being increasingly accepted as part of the kidney allocation programme. The aims of this study are to evaluate the effect of donor and recipient age on transplant outcomes and to determine the effect of changing existing allocation criteria to allocation based on age matching of donors and recipients on total graft years of function. Methods. Using the Australia and New Zealand Dialysis and Transplant Registry, all DD kidney transplant recipients in Australia and New Zealand between 1991 and 2006 were analysed (n = 4616). Outcomes analysed were overall graft failure, death with functioning graft and serum creatinine. We calculated the mean time to graft loss ('years of graft function') for donor and recipient age cutoffs as 60 and 55 years, respectively, over up to 16 years follow-up. We then examined the gain in graft years if allolder kidneys were allocated to older recipients. Results. Older donors were associated with higher risk of overall graft failure [adjusted hazard ratio (HR) = 1.79, 95% confidence interval (95% CI) = 1.45, 2.21 and HR = 1.29, 95% CI = 1.09, 1.53, respectively] at 1-8 years posttransplant and higher serum creatinine at 1 and 5 years posttransplant (mean differences 32.74 μmol/L, 95% CI 27.60, 37.89 and 38.17 μmol/L, 95% CI 27.58, 48.77, respectively). Overall, young and old recipients with young donor kidneys have an additional two to three mean graft years compared to those receiving older donor kidneys. Conclusion. Donor and recipient age matching is an effective method of organ allocation to improve total graft years. [ABSTRACT FROM AUTHOR]