Tacrolimus dose, blood concentrations and acute nephrotoxicity, but not CYP3A5/ABCB1 genetics, are associated with allograft tacrolimus concentrations in renal transplant recipients.

Aims: Long-term use of the immunosuppressant tacrolimus is limited by nephrotoxicity. Following renal transplantation, the risk of nephrotoxicity may be determined more by allograft than by blood tacrolimus concentrations, and thus may be affected by donor CYP3A5 and ABCB1 genetics. Little is known regarding factors that determine tacrolimus intrarenal exposure.

Effect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial.

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).

Evidence-based practice: Guidance for using everolimus in combination with low-exposure calcineurin inhibitors as initial immunosuppression in kidney transplant patients.

The mammalian target of rapamycin (mTOR) inhibitor, everolimus, in combination with reduced-exposure calcineurin inhibitor (CNI), has been demonstrated in clinical trials to have comparable efficacy in low-to-moderate immunological risk kidney transplant recipients to the Standard of Care, mycophenolic acid (MPA) in combination with standard-exposure CNI. Current treatment guidelines consider mTOR inhibitors to be a second-line therapy in the majority of cases; however, given that everolimus-based regimens are associated with a reduced rate of viral infections after transplantation, their wider use could have great benefits for kidney transplant patients. In this evidence-based practice guideline, we consider the de novo use of everolimus in kidney transplant recipients.

Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis.

Background: Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients.

Methods: To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function.

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies.

The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9.

Successful pregnancy in a recipient of an ABO-incompatible renal allograft.

Kidney transplantation restores fertility in patients with end-stage renal disease, with many successful pregnancies after kidney transplantation being reported. , there are little data regarding pregnancy in women transplanted under modern-era desensitisation protocols that utilise rituximab, plasma exchange and intravenous immunoglobulin, including ABO-incompatible transplants. Pregnancies in ABO-incompatible recipients can pose new challenges from an immunological perspective.

Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.

Background: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail.

Methods: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids.

Results: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.

Relationship between allograft cyclosporin concentrations and P-glycoprotein expression in the 1st month following renal transplantation.

The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression.

Weekend effect on early allograft outcome after kidney transplantation- a multi-centre cohort study.

Weekend surgery may be associated with a higher risk of early complications, but the effect of the timing of kidney transplant surgery on early allograft outcome remains uncertain. The aim of this study is to evaluate whether the association between weekend transplant surgery and allograft failure was modified by prevalent vascular disease. Using data from the Australia and New Zealand Dialysis and Transplant registry, we examined the association between weekend status and 90-day and 1-year allograft failure in deceased donor transplant recipients between 1994-2012.

Everolimus and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Registry-based 10-year Follow-up of 5 Randomized Trials.

Background: Data regarding the long-term efficacy of everolimus-based immunosuppression for kidney transplantation are lacking. Existing randomized controlled trials are limited by short follow-up duration which limits capacity to assess impact on graft and patient survival.

Methods: We linked individual trial participants to the Australian and New Zealand Dialysis and Transplant Registry.

De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients: A trial-based linkage study.

Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks.

Kidney transplant graft outcomes in 379 257 recipients on 3 continents.

Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow-up registry data from 1988-2014 for 379 257 recipients of first kidney-only transplants using Cox regression.

Predicting Expected Organ Donor Numbers in Australian Hospitals Outside of the Donate-Life Network Using the ANZICS Adult Patient Database.

Background: The majority of organ donations in Australia occur in the DonateLife Network of hospitals, but limited monitoring at other sites may allow donation opportunities to be missed. Our aim was to estimate expected donor numbers using routinely collected data from the Australian and New Zealand Intensive Care Society Adult Patient Database and determine whether unrecognized potential donors might exist in non-DonateLife hospitals.

Methods: All deaths at 150 Australian intensive care units (ICUs) contributing to the Australian and New Zealand Intensive Care Society Adult Patient Database were analyzed between January 2010 and December 2015.

Association Between Delayed Graft Function and Graft Loss in Donation After Cardiac Death Kidney Transplants-A Paired Kidney Registry Analysis.

Background: Delayed graft function (DGF) is an established complication after donation after cardiac death (DCD) kidney transplants, but the impact of DGF on graft outcomes is uncertain. To minimize donor variability and bias, a paired donor kidney analysis was undertaken where 1 kidney developed DGF and the other did not develop DGF using data from the Australia and New Zealand Dialysis and Transplant Registry.

Methods: Using paired DCD kidney data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between DGF, graft and patient outcomes between 1994 and 2012 using adjusted Cox regression models.

The risk of cancer in kidney transplant recipients may be reduced in those maintained on everolimus and reduced cyclosporine.

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.

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation.

Background: Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients.

Methods: The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients.

Unlabelled: Calcineurin inhibitor-associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients.

Methods: This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus.

HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients.

Background And Objectives: The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.

Maternal compared with paternal donor kidneys are associated with poorer graft outcomes after kidney transplantation.

Noninherited maternal human leukocyte antigens may be less detrimental on allograft outcomes after kidney transplantation compared with noninherited paternal antigens, but this association in the era of modern immunosuppression remains unknown. Here we determine the association between parental donor kidneys, acute rejection, and graft failure in primary live-donor parental kidney transplant recipients using data from the Australia and New Zealand Dialysis and Transplant Registry between 1997 and 2012. Of the 1139 recipients followed for a median of 7.

Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors.

Background And Objectives: The quality and age of donor organs are known to have a major effect on patient and graft outcomes, but it is uncertain whether this association is uniform for all recipients. We aimed to determine whether the use of expanded criteria deceased donor (ECD) kidneys for transplantation compared with standard criteria deceased donor (SCD) kidneys has a different association with survival in younger (age <60 years old) compared with older (age ≥60 years old) recipients.

Design, Setting, Participants, & Measurements: Using data from the Australian and New Zealand Dialysis and Transplant Registry (1997-2009), we compared the risk of all-cause mortality and death with functioning graft among younger and older recipients who had received either an SCD or an ECD kidney using the adjusted Cox proportional hazard models.

A Single Center Experience With Adult Dual Kidney Transplant.

Objectives: Our renal transplant center in South Australian has been at the forefront of dual kidney transplants in Australia. In this study, we reviewed the 17 adult dual kidney transplants performed at our center between 1998 and 2014.

Materials And Methods: We retrospectively reviewed the 17 adult dual kidney transplants performed at our center since 1998 and report data pertaining to donor demographics, preimplant function, and histology of donor kidneys, as well as postoperative outcomes of transplant recipients.

Cell-mediated and humoral acute vascular rejection and graft loss: A registry study.

Aims: Rejection of renal allografts following transplantation continues to be a major impediment to long-term graft survival. Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or acute humoral rejection (AHR) have dissimilar outcomes. The aim of this registry study was to examine the association between subtypes of AVR and graft loss.

Renal-limited thrombotic microangiopathy and acute interstitial nephritis with a single dose of quinine.

Quinine has been reported to cause acute kidney injury by various mechanisms. The response to quinine can result in a spectrum of problems ranging from isolated thrombocytopenia to thrombotic microangiopathy (TMA) to disseminated intravascular coagulation. Quinine has also been reported to cause acute interstitial nephritis (AIN).

Efficacy of everolimus with reduced-exposure cyclosporine in de novo kidney transplant patients at increased risk for efficacy events: analysis of a randomized trial.

The efficacy of de novo everolimus with reduced-exposure calcineurin inhibitor (CNI) was examined in kidney transplant subpopulations from the A2309 study that were identified to be at increased risk for efficacy events. A2309 was a 24-month, multicenter, open-label trial in which 833 de novo kidney transplant recipients were randomized to everolimus targeting 3-8 or 6-12 ng/ml with reduced-exposure cyclosporine (CsA), or mycophenolic acid (MPA) with standard-exposure CsA, all with basiliximab induction. The composite efficacy endpoint was treated biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up.