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The first living and deceased donor kidney transplants were performed in Australia in 1965. In the 56 years since, kidney transplantation has become a cornerstone of treatment for kidney failure in Australia and is performed in most capital cities. In 2019, the most recent year for which complete data are available, 1104 kidney transplants (44 per million population [pmp]) were performed, 16% growth (and an additional 4 pmp) from just 4 years prior (1). This reflects a transplantation rate of 7.1 transplants/100 dialysis-years (all patients on dialysis included in the denominator) or 11.6 transplants/100 dialysis-years (only patients on dialysis aged 15–64 years included in the denominator) (2). Of the 1104 kidney transplants performed in 2019, 22% were from living donors, including 40 patients transplanted via paired kidney exchange (3). The total number of people living with a functioning transplant in Australia was 12,815 (505 pmp) in 2019, up from 10,479 (440 pmp) in 2015, and 8510 (386 pmp) in 2010 (1). Despite annual growth in the number of transplants performed, similar increases in the number of candidates waitlisted have prevented any reduction in the size of the waitlist. In 2019 there were 1100 people active on the kidney transplant waitlist, largely unchanged from 1145 in 2014 (2). Recognizing the importance of transplantation, in 2009 the Australian government established the Organ and Tissue Authority (OTA). The OTA was charged with maximizing the rate of organ donation from deceased donors for transplantation in Australia, which lagged international best practice at that point. To do this, the OTA adopted elements of the “Spanish model,” including the optimization of hospital infrastructure such that potential donors could be more easily recognized, establishing organ donor specialists in all major intensive care units, and improving donor and family consent rates through targeted training (4). By …

Background Kaposi’s sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. Case presentation A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. Conclusion This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi’s sarcoma.

Aim Rates of simultaneous liver and kidney transplantation (SLKT) have increased, but indications for SLKT remain poorly defined. Additional data are needed to determine which patients benefit from SLKT to best direct use of scarce donor kidneys. Methods Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) database for all SLKT performed until the end of 2017. Patients were divided by pretransplant dialysis status into no dialysis before SLKT (preemptive kidney transplant) and any dialysis before SLKT (nonpreemptive). Baseline characteristics and outcomes were compared. Results Between 1989 and 2017, inclusive, 84 SLKT procedures were performed in Australia, of which 24% were preemptive. Preemptive and nonpreemptive SLKT recipients did not significantly differ in age (P = .267), sex (P = .526), or ethnicity (P = .870). Over a median follow-up time of 4.5 years, preemptively transplanted patients had a statistically equivalent risk of kidney graft failure (hazard ratio (HR) 1.83, 95% confidence interval [CI]: 0.36-12.86, P = .474) and all-cause mortality (HR 1.69, 95% CI: 0.51-5.6, P = .226) compared to nonpreemptive patients. Overall, 1- and 5-year survival rates for all SLKTs were 92% (95% CI: 86-96) and 60% (95% CI: 45-75), respectively. Conclusion Kidney graft and overall patient survival were similar between patients with preemptive kidney transplant and those who were dialysis dependent.

Background Quality-of-life is an essential outcome for clinical care. Both chronic kidney disease (CKD) and diabetes have been associated with poorer quality-of-life. The combined impact of having both diseases is less well understood. As diabetes is the most common cause of CKD, it is imperative that we deepen our understanding of their joint impact. Methods This was a prospective, longitudinal cohort study of community-based Australians aged ≥25 years who participated in the Australian Diabetes, Obesity and Lifestyle study. Quality-of-life was measured by physical component summary (PCS) and mental component summary sub-scores of the Short Form (36) Health Survey. Univariate and multivariate linear mixed effect regressions were performed. Results Of the 11 081 participants with quality-of-life measurements at baseline, 1112 had CKD, 1001 had diabetes and of these 271 had both. Of the 1112 with CKD 421 had Stage 1, 314 had Stage 2, 346 had Stage 3 and 31 had Stages 4/5. Adjusted linear mixed effect models showed baseline PCS was lower for those with both CKD and diabetes compared with either disease alone (P Conclusions The combination of CKD and diabetes has a powerful adverse impact on quality-of-life, and participants with both diseases had significantly poorer quality-of-life than those with one condition.

Background Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required. Case presentation Two patients underwent SLKT and received our centre’s standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant. Conclusions These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.

Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998-2017. Patients were transplanted preemptively (n = 1435) or after receiving up to 6 months of dialysis (n = 712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left-truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min per 1.73 m2 in the non-pre-emptive, and 9.6 mL/min per 1.73 m2 in the preemptive group. In the matched cohort (n = 1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non-pre-emptive 1.12 (95% confidence interval [CI] 0.79-1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4 mL/min per 1.73 m2 /year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.

ObjectivesDevelopment of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box (iBox) as a surrogate endpoint to the TRANSFORM Study, a large randomised controlled trial, to project individual patient long-term kidney allograft survival from 1 year to 11 years after randomisation.DesignPost-hoc analysis of a randomised open-label controlled trial.SettingMulticentre study including 186 centres in 42 countries worldwide.Participants2037 de novo kidney transplant recipients.InterventionParticipants were randomised (1:1) to receive everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolic acid with standard-exposure CNI (MPA+sCNI).Primary outcome measureThe iBox scores were computed for each participant at 1 year after randomisation using functional, immunological and histological parameters. Individual long-term death-censored allograft survival over 4, 6 and 11 years after randomisation was projected with the iBox risk-prognostication system.ResultsOverall, 940 patients receiving EVR+rCNI and 932 receiving MPA+sCNI completed the 1-year visit. iBox scores generated at 1 year yielded graft survival prediction rates of 90.9% vs 92.1%, 87.9% vs 89.5%, and 80.0% vs 82.4% in the EVR+rCNI versus MPA+sCNI arms at 4, 6, and 11 years post-randomisation, respectively (all differences below the 10% non-inferiority margin defined by study protocol). Inclusion of immunological and histological Banff diagnoses parameters in iBox scores resulted in comparable and non-inferior predicted graft survival for both treatments.ConclusionsThis proof-of-concept study provides the first application of a validated prognostication system as a surrogate endpoint in the field of transplantation. The iBox system, by projecting kidney allograft survival up to 11 years post-randomisation, confirms the non-inferiority of EVR+rCNI versus MPA+sCNI regimen. Given the current process engaged for surrogate endpoints qualification, this study illustrates the potential to fast track development of pharmaceutical agents.Trial registration numberTRANSFORM trial: NCT01950819.iBox prognostication system: NCT03474003.

Delayed graft function (DGF) after kidney transplantation is associated with inferior outcomes and higher healthcare costs. DGF is currently defined as the requirement for dialysis within seven days post-transplant; however, this definition is subjective and nonspecific. Novel biomarkers have potential to improve objectivity and enable earlier diagnosis of DGF. We reviewed the literature to describe the range of novel biomarkers previously studied to predict DGF. We identified marked heterogeneity and low reporting quality of published studies. Among the novel biomarkers, serum NGAL had the greatest potential as a biomarker to predict DGF, but requires further assessment and validation through larger scale studies of diagnostic test performance. Given inadequacies in the dialysis-based definition, coupled with the high incidence and impact of DGF, such studies should be pursued.

Background: Early chronic kidney disease (CKD) diagnosis in patients with type 2 diabetes (T2D) followed by guideline-recommended interventions are key to slowing CKD progression, but adherence to screening recommendations is suboptimal. Inside CKD models the global clinical and economic burden of CKD using country-specific, patient-level microsimulation models. We model the effects of targeted implementation of urine albumin:creatinine ratio (UACR) measurement and intervention in patients with T2D. Methods: We used the Inside CKD microsimulation to model the impact of measuring UACR during routine primary care visits with subsequent intervention in patients with T2D aged ≥45 years, versus current practice. Virtual populations were constructed using published country-specific data on demographics, CKD, T2D, comorbidities and complications. Results: Preliminary data for three countries show that in 2020-2025, measurement of UACR in patients with T2D would prevent CKD progression to stages 3b-5 in 80 000 patients in the UK, 350 000 in the US and 70 000 in Canada (Figure). Associated cost savings would be £90M, $5B and C$1.7B. More countries will be analysed. Conclusion: Preliminary data show that routine UACR measurement with subsequent intervention could potentially reduce the global burden of CKD and healthcare costs in patients with T2D, and improve outcomes. Disclosure S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen. S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca

Background: Inside CKD aims to model the future global clinical and economic burden of chronic kidney disease (CKD). Type 2 diabetes (T2D) is a leading cause of CKD, and concomitant CKD and T2D place a significant burden on healthcare systems worldwide. Methods: We used the Inside CKD country-specific, patient-level microsimulation to model global healthcare costs for patients with concomitant CKD and T2D from 2020 to 2025. We constructed virtual populations using country-specific data including demographics, prevalence of CKD (by stage), T2D and complications, and direct costs, from multiple published sources (e.g., NHANES for US; HSE for UK). Results: Preliminary results from three countries show that annual healthcare costs for patients with both CKD and T2D are expected to increase from 2020 to 2025 (US, $51.1B-95.3B; Canada, C$6.5B-11.5B; UK, £2.3B-2.7B) (Figure). Costs attributable to CKD stage 4 are expected to increase the most (US, 4-9% of overall costs; Canada, 9-13%; UK, 7-11%). Conclusion: Healthcare costs for patients with both CKD and T2D are projected to increase in the UK, US and Canada from 2020 to 2025. Later CKD stages are associated with more pronounced cost increases, likely due to both increased prevalence and greater treatment complexity. Early diagnosis and interventions to slow CKD progression are needed to reduce the economic burden of concomitant stage 3-5 CKD and T2D. Disclosure J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen . S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca

Introduction Post-transplant lymphoproliferative disorders (PTLD) are aggressive lymphomas which occur in solid organ transplant recipients and cause significant mortality. In the era of positron emission tomography (PET) staging and rituximab (R), there is limited real-world data on treatment outcomes and the incidence of graft rejection after reduction in immunosuppression (RIS) has not been well defined. We report real-world outcomes of monomorphic diffuse large B cell lymphoma (DLBCL), the commonest histological subtype of PTLD in which treatment is most likely to be standardised. Methods We conducted a multicentre retrospective study across 11 Australian tertiary referral centres. Inclusion criteria were: (1) age ≥ 18 years with history of solid organ transplant; (2) a diagnosis of monomorphic DLBCL PTLD between January 2004 and December 2017; (3) staging with PET. We examined responses based on treatment: (1) 'R-primary' was defined as patients receiving initial rituximab monotherapy followed by further rituximab monotherapy for patients in remission or R-CHOP chemotherapy for patients with persistent or progressive disease; (2) 'R-chemotherapy' was defined as patients who received rituximab-based chemotherapy at diagnosis. Response assessment was defined according to current international lymphoma criteria (complete metabolic remission (CMR) = Deauville score 1-3). We examined the incidence of clinical and biopsy-proven graft rejection during and after PTLD diagnosis (early Results 91 DLBCL patients were identified. The median follow-up of living patients was 4.7 years (range 0.5-14.5 years). Baseline characteristics for all patients are shown in Table 1. Management approaches: Reduction in immunosuppression (RIS) was used in 88% of patients and rituximab (R) +/- chemotherapy in almost all patients (98%, n=89). Rituximab monotherapy (R-primary) was the first treatment in 24 patients (35%). Of these, 20 had PET restaging after rituximab and 9 patients (45%) achieved CMR and did not require chemotherapy. CMR rate rose to 71% with the subsequent addition of R-CHOP in R-primary non-responders. For patients initially treated with R-CHOP, the CMR rate was 76%. The incidence of graft rejection was 9% for the entire duration of follow up (n=4 biopsy-proven; n=4 clinically suspected) with 3 cases occurring within one year of PTLD diagnosis (Table 2). Survival and Prognostic Factors For the entire cohort, 3-y OS and PFS were 72% and 69%, respectively. There was no significant difference in OS between patients treated with an R-primary vs R-chemotherapy approach (P=0.13). Treatment-related mortality (TRM) was 7% with no significant difference between R-primary and R-chemotherapy approach (p=0.97). Outcomes for patients without CNS involvement (n=68) were comparable to patients with CNS involvement (n=23): 3-y OS 72.5% non-CNS vs 73.1% CNS; (P=0.78) - Figure 1. In multivariate analysis, elevated LDH (HR=3.58, P=0.025 [95% CI 1.17-10.8]) and ECOG ≥2 (HR=3.46, P=0.006 [95% CI 1.43-8.33]) were identified as predictors of worse OS. End of Treatment (EoT) PET imaging A total of 60 patients (66%) had EoT PET. Reasons for not performing an EoT PET (n=31) were: 7 MRI scans for CNS disease, 2 CT scans without PET, 10 patients without imaging (6 PD, 4 TRM), 12 missing data. Achieving CMR at EoT PET was predictive of OS (3-year OS PET negative 92.9% vs PET positive 51.4%; P=0.035) and only 5% of these patients relapsed (Figure 2). Conclusions In one of the largest real-world assessments of monomorphic DLBCL PTLD in the modern era of rituximab and PET imaging our data demonstrate: (1) similar response rate, OS and TRM compared to the PTLD-1 trial (Trappe et al, 2017); (2) the safety and efficacy of an R-primary approach; (3) similar OS for patients with CNS involvement compared to those with systemic lymphoma; (4) lower incidence of graft rejection than previously reported; and (5) achieving CMR at EOT PET is predictive of OS. This demonstrates that RIS and rituximab-based treatment is safe with a low likelihood of graft rejection and effective with a high cure rate for patients achieving CMR. Disclosures Tobin: Gilead: Research Funding. Hamad:Novartis: Honoraria; Abbvie: Honoraria. Talaulikar:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Cheah:Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding; Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria. Lee:Celgene/BMS: Consultancy; Amgen: Consultancy; Janssen: Consultancy. Strasser:Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ispen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mollee:Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees.

Summary The COVID‐19 pandemic has challenged the delivery of health services. Telehealth allows delivery of care without in‐person contacts and minimizes the risk of vial transmission. We aimed to describe the perspectives of kidney transplant recipients on the benefits, challenges, and risks of telehealth. We conducted five online focus groups with 34 kidney transplant recipients who had experienced a telehealth appointment. Transcripts were thematically analyzed. We identified five themes: minimizing burden (convenient and easy, efficiency of appointments, reducing exposure to risk, limiting work disruptions, and alleviating financial burden); attuning to individual context (depending on stability of health, respect patient choice of care, and ensuring a conducive environment); protecting personal connection and trust (requires established rapport with clinicians, hampering honest conversations, diminished attentiveness without incidental interactions, reassurance of follow‐up, and missed opportunity to share lived experience); empowerment and readiness (increased responsibility for self‐management, confidence in physical assessment, mental preparedness, and forced independence); navigating technical challenges (interrupted communication, new and daunting technologies, and cognizant of patient digital literacy). Telehealth is convenient and minimizes time, financial, and overall treatment burden. Telehealth should ideally be available after the pandemic, be provided by a trusted nephrologist and supported with resources to help patients prepare for appointments., Kidney transplant recipients participated in focus groups to determine their experience with telehealth which replaced their face‐to‐face nephrology clinics during the COVID‐19 pandemic. Recipients believe that telehealth should be available after the pandemic.

Background Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. Case presentation A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1–0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. Conclusions This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.

Background: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision-making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. Methods: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During Round 2 and 3, participants re-rated the outcomes after reviewing their own score, the distribution of the respondents’ scores, and comments. We calculated the median, mean, and proportion rating 7-9 (critically important), and analyzed comments thematically. Results: 1018 participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed Round 1, and 779 (77%) completed Round 3. The top eight outcomes that met the consensus criteria in Round 3 (mean ≥7.5, median ≥8 and proportion >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin) and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to six outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified five themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. Conclusions: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation.

Recurrent glomerulonephritis after kidney transplantation is a feared complication because it is unpredictable and may have a negative impact on graft outcomes. To better understand this we collected data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry accumulated over 30 years. The incidence, risk factors, and outcomes of recurrent glomerulonephritis in transplant recipients were determined using adjusted Cox proportional hazard and competing risk modeling. A total of 6,597 recipients with biopsy-proven glomerulonephritis as the primary cause of end-stage kidney disease were followed for 51,871 person-years (median duration 7.7 years). The four most common types of glomerulonephritis were IgA nephropathy in 2501 patients, focal segmental glomerulosclerosis (FSGS) in 1403, membranous in 376, and membranoproliferative (MPGN) nephropathy in 357 patients. Among these four types, recurrence was reported in 479 of 4637 patients, and of these, 212 lost their allograft due to recurrence. Older age at transplantation (adjusted hazard ratio [per year increase] 0.96 [95% confidence interval 0.95 – 0.97]) was associated with a lower risk of recurrence. Significantly, the five-year graft survival was 30% for recipients with recurrent MPGN and 57-59% for recipients with FSGS, IgA, and membranous nephropathy. Transplant recipients with recurrent disease were twice as likely to lose their allografts compared to those without recurrence (adjusted hazard ratio 2.04 [1.81-2.31]). Thus, recurrent glomerulonephritis remains a significant cause of graft loss in transplant recipients.

AIMS Uncertainties about the role of cystatin C-based estimated glomerular filtration rate (eGFR) in the prediction of cardiovascular disease (CVD) beyond traditional CVD risk factors remain. We assessed contributions of eGFR to CVD and mortality in the general population. METHODS Using 14 year follow-up data on 9353 adults without a reported history of CVD from the Australian Diabetes, Obesity and Lifestyle study, we assessed the contributions of eGFR (assessed by cystatin C (eGFRcysC ) and serum creatinine (eGFRcr ) and albuminuria (uACR) to total and CVD mortality. RESULTS After adjusting for age, sex, CVD risk factors and uACR, compared with an eGFRcysC >90 mL/min per 1.73 m2 , eGFRcysC

Aim We aimed to describe the impact and experience of being deemed ineligible as a living kidney donor. Methods Semi-structured interviews were conducted with 27 ineligible donor candidates. Transcripts were analysed thematically. Results Seven themes were identified: deriving health and relationship benefits in the process (strengthening emotional connection, identifying problematic health conditions); devastating loss and disappointment (harbouring guilt over personal failings, shattering confidence and hope, undermining relationships with extended family and friends, disrupting home dynamics); constrained within a rigid system (denied autonomy, resorting to other avenues); acknowledging as matter of fact (accepting the clinical decision, reassured by preventing a poor outcome); reluctant to relinquish the donor identity (unable to fulfil family duty, having the donor role stolen, holding onto other opportunities to donate); uncertainty in unpredictability, inconsistency and ambiguities (frustrated by inefficiencies, questioning clinician motivation, suspended donor status, unfairness in changeable eligibility criteria, unresolved concerns and questions of own health); and abandoned in despair (lacking practical support to meet eligibility criteria, ill prepared for rejection, dismissed and discarded by the system). Conclusion Being deemed unsuitable for donation took an emotional toll on ineligible donor candidates who felt immense guilt for 'failing' the potential recipient. Ineligible donor candidates were frustrated and angry with the perceived lack of support from clinicians and rigidity of the evaluation process. Informing potential donors of available services, including psychological support, communicating the decision sensitively and with sufficient time, and full disclosure of their health status, may contribute to improved adjustment following the ineligibility decision.

Young adult onset type 2 diabetes (YT2DM) is an aggressive disease. Cross-sectional studies have shown a higher prevalence of albuminuria in YT2DM compared to age-matched young adults with T1DM (YT1DM). Whether this translates to poorer long-term renal outcomes has not been widely studied. We aimed (i) to examine progression to renal replacement therapy (RRT) and renal-related death (RRD) in our young adult population, and (ii) to examine survival on RRT for those individuals who reached end stage renal disease. We performed probabilistic linkage of prospectively collected data from the RPA Diabetes Centre eMR to the Australian National Death Index and the Australian and New Zealand Dialysis and Transplant Registry up to 31/12/2015. In our patient cohort diagnosed between the ages of 15 and 35 years, 1,248 had YT1DM and 1,534 had YT2DM. After a median (IQR) observation of 13.6 (6.9-20.7) years, 56 (4.5%) of YT1DM vs. 98 (6.4%) of YT2DM reached the combined renal end-point of RRT/RRD. Analysis of Kaplan-Meier survival curves demonstrated a greater rate of progression of renal disease in YT2DM (Log-rank p=0.003). Cox proportional hazard modelling of RRT/RRD with adjustment for gender, ethnicity and duration of diabetes exposure was undertaken. The HR (95% CI) for an adverse renal outcome in YT2DM relative to YT1DM was 2.0 (1.4-2.9), p Disclosure T. Middleton: Other Relationship; Self; AstraZeneca. S. Chadban: None. L.M. Molyneaux: None. M.I. D'Souza: None. M.I. Constantino: None. D. Yue: None. M. McGill: None. T. Wu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. S.M. Twigg: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; AstraZeneca. Research Support; Self; Abbott. Speaker's Bureau; Self; Abbott, AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. J. Wong: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; AstraZeneca, Lilly Diabetes.

Renal failure is a common feature of multiple myeloma affecting 20-55% of patients at the initial presentation and is being associated with a significant increase in morbidity and mortality. Renal transplantation for patients with multiple myeloma is rarely considered given the incurable nature of the disease, the risk of post-transplant disease progression and perceived high risk of infections. Here we report a 57-year-old man with end-stage renal failure attributed to presumed IgA nephropathy, with pre-existing stable multiple myeloma, who received a kidney transplant from a two haplotype-matched sibling. Transplantation has been successful and with excellent kidney function and stable multiple myeloma 6 years post-transplant. This case highlights the potential benefits of renal transplantation in highly selected patients with multiple myeloma.

ATHENA, published in this edition of Kidney International, is the third contemporary, multicenter, randomized, controlled trial to compare de novo use of everolimus, calcineurin inhibitor, and steroids to our current standard of care, mycophenolate, tacrolimus, and steroids, in kidney transplant recipients. This commentary highlights the strengths and significant weaknesses of ATHENA. It then seeks to distill the key messages from the 3 trials, ATHENA, TRANSFORM, and US92, and considers the role of everolimus in kidney transplantation today. Ultimately, the 3 trials demonstrate that everolimus with reduced-concentration tacrolimus and steroids provide a viable alternative to our current standard of care.

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes. ispartof: pages:1053-1068 ispartof: Kidney Int vol:94 issue:6 pages:1053-1068 ispartof: location:United States status: published

BackgroundAcute kidney injury (AKI) is predominantly a disease of low and middle-income countries. Despite this, there is a particular paucity of data regarding AKI in Africa. Most published studies were conducted prior to the most recent Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI. This prospective, observational, cohort study examines AKI amongst newly admitted acute medical inpatients in a large, urban, tertiary hospital in Harare, Zimbabwe.MethodsAll newly admitted, adult, medical patients in separate, randomly selected, 24-hour periods were included. Baseline demographic information, comorbidities, nephrotoxic medication use, and reason for admission were recorded on a standardised data capture record. A serum creatinine measurement was performed on all patients at the time of admission and again after 48 hours. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and AKI was defined using the most recent KDIGO definition as an increase in the serum creatinine of greater than 26.5μmol/L within 48 hours, with admission creatinine used as a baseline measurement.Results253 patients were included in the analysis; 137 patients (54.2%) were female; 100 patients (39.5%) had HIV infection. 36 patients (14.2%) met the KDIGO criteria for AKI during the 48-hour follow-up period. AKI was more common among males (19.8% vs 9.5%; p = 0.019). The AKI group had a higher serum creatinine at presentation than those without AKI (296.5μmol/L vs 91.0μmol/L; pConclusionsKDIGO-defined AKI was common in hospitalised patients in Sub-Saharan Africa and was predicted by male sex, a history of comorbid hypertension and a history of comorbid chronic kidney disease.

Background The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population. Methods Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n = 6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1 + transplant characteristics; Model 3: Model 2 + recipient characteristics) and compared using Harrell’s C-statistics for the outcomes of death-censored graft survival and overall graft survival. Results Both scores were strongly associated with death-censored and overall graft survival (P Conclusions The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.

Background: Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis but complications and side-effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but it is inconsistently and infrequently measured in trials. We convened a consensus workshop on establishing a core outcome measure for life participation for use in all trials in kidney transplantation. Methods: Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from eight countries participated in six facilitated breakout group discussions. Transcripts were analyzed thematically. Results: Four themes were identified. Returning to normality conveyed the patients’ goals to fulfill their given roles (i.e. in their family, work, and community) and re-establish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of ‘life’ explicitly acknowledged life participation as a subjective concept that could refer to different activities (e.g. employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations post-transplant (e.g. due to complications and side-effects) distinguished between experiences in the first year post-transplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. Conclusions: A feasible and validated core outcome measure for life participation is needed so critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision-making and care of recipients.

Background and objectives Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. Design, setting, participants, & measurements Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. Results Across 14 groups, 123 donors aged 27–78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0–1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. Conclusions Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings.

Background Ensuring donor wellbeing warrants ongoing monitoring after living kidney donation. However, there is considerable variability in donor follow-up processes, including information provided to donors regarding self-care. Loss to follow-up is common, suggesting that the aims and benefits of monitoring and follow-up may not be apparent. We aimed to describe the experiences and expectations of living kidney donors regarding follow-up and self-care after donation. Methods Participants from 3 transplant centers in Australia and Canada participated in 14 focus groups (n = 123). Transcripts were analyzed thematically. Results We identified 4 themes: lacking identification as a patient (invincibility and confidence in health, immediate return to normality, avoid burdening specialty services, redundancy of specialist attention, unnecessary travel), empowerment for health (self-preservation for devastating consequences, self-advocacy and education, needing lifestyle advice, tracking own results), safety net and reassurance (availability of psychosocial support, confidence in kidney-focused care, continuity and rapport, and access to waitlist priority), and neglect and inattention (unrecognized ongoing debilitations, primary focus on recipient, hospital abandonment, overlooking individual priorities, disconnected from system, coping with dual roles, and lacking support for financial consequences). Conclusions Living kidney donors who felt well and confident about their health regarded specialist follow-up as largely unnecessary. However, some felt they did not receive adequate medical attention, were prematurely detached from the health system, or held unresolved anxieties about the consequences of their decision to donate. Ongoing access to healthcare, psychosocial support, and education may reassure donors that any risks to their health are minimized.

Diabetes mellitus is now the most common cause of new cases of end-stage kidney disease treated with kidney replacement therapy in Australia. In addition to the approximately 5000 Australians receiving maintenance dialysis or living with a kidney transplant as a consequence of diabetes, many die from untreated end-stage kidney disease due to diabetes (DM-ESKD) each year. For every Australian receiving renal replacement therapy due to diabetes, at least 50 others have earlier stages of diabetic kidney disease (DKD). Based on projected increases in type 2 diabetes prevalence, the size of this underlying population with DKD will potentially exceed half a million by 2025. In addition to the risk of developing DM-ESKD, this population is at increased risk of premature cardiovascular morbidity and all-cause mortality. Higher rates of hospitalization, use of specialist services and prescription drugs mean that those with DKD also incur significantly greater health care costs compared with those with diabetes or chronic kidney disease alone. However, in contrast to the increasing prevalence of diabetes and early stages of DKD, recent trends in the incidence of DM-ESKD suggest that better management in the earlier stages of DKD has been successful in slowing rates of disease progression. Simultaneous improvements in use of renin-angiotensin inhibitors and improved glycaemic and blood pressure control are likely to be largely responsible for this trend. Primary prevention, maximizing early detection of DKD and optimal management of diabetes and kidney disease hold great potential to attenuate the future health burden attributable to DKD in Australia.

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that carries a high morbidity and mortality. The 'two hit theory' suggests that long term deterioration of the peritoneum combined with intraperitoneal inflammation is needed in the pathogenesis of EPS. For unclear reasons, post transplantation EPS is being increasingly reported in patients previously on PD. To date, there is no proven effective therapy with an absence of randomised controlled trials. Individual case reports and small case series have reported on the use of tamoxifen and corticosteroids for medical management of EPS. The use of everolimus has been reported in a single case, and never in the setting of renal transplantation. Here, we present the first case of post-transplant encapsulating peritoneal sclerosis treated successfully with a combination of everolimus, tamoxifen, low dose corticosteroid and surgery.

Background and objectivesMany donors and recipients report an improved bond posttransplantation; however, unexpected conflicts and tension may also occur. Insights into the lived experiences of the donor–recipient relationship can inform strategies for interventions and support. We aimed to describe donor and recipient expectations and experiences of their relationship before and after living kidney donor transplantation.Design, setting and participantsSemistructured interviews were conducted with 16 donor–recipient pairs before the transplant and 11–14 months post-transplant. Transcripts were analysed thematically.ResultsWe identified seven themes (with respective subthemes): donation as enacting familial responsibility for care; analytical decision making to mitigate regret (avoiding anticipated regret and maintaining control, removing emotional impulsivity); strengthened interpersonal ties (gaining a deeper appreciation among family members, stronger empathy for each other, improving social participation); instability of relational impacts (anger and aggression threatening dynamics, unanticipated stress and emotional lability, triggering familial tension); renegotiating social roles (unexpected continuation of caregiving responsibilities, inability to relinquish the caregiving role, disappointment with unfulfilled renewal of intimacy, dissatisfaction over discrepant energy levels); guilt over unmet expectations and inevitability of the gift relationship (vague and transient indebtedness, expectation of reciprocity, transferring kidney ownership).ConclusionsDonor–recipient relationships may be improved through increased empathy, appreciation, and ability to participate in life together; however, unfulfilled expectations and behavioural and emotional changes in recipients (a side effect related to immunosuppression) remain unresolved consequences of living kidney donor transplantation. Education and counselling to help donors and recipients adjust to potential changes in relationship dynamics may help protect and foster relational stability postdonation.

Serum creatinine is routinely used to monitor renal function in transplant recipients. External factors including diet, exercise and hydration status can also influence serum creatinine concentration on a day-to-day basis. We describe a case of a patient whose serum creatinine increased from 128 to 171 μmol/L after ingestion of creatinine-rich (3098 μmol/L) soup. A renal biopsy was performed but revealed no cause for the rise in creatinine and by the next day, serum creatinine had returned to baseline. We conducted two experiments to examine the effect of soup ingestion by healthy volunteers. We measured the creatinine concentration of various store-bought stock preparations and found creatinine concentrations less than one-quarter of that contained in our patient's homemade soup. A creatinine-rich soup (4334 μmol/L) was ingested by six healthy volunteers age 33 (± 6.5) years with baseline normal serum creatinine 68 (± 14) μmol/L. Mean (standard deviation) serum creatinine increased to 77 (± 11) μmol/L 4 hours after soup ingestion (P = 0.0015, paired t-test). Mean (standard deviation) creatinine clearance, extrapolated from the 4 hour urine collection following soup ingestion, was high (267 ± 198 mL/min) exhibiting a supra-normal creatinine clearance. The rate of serum creatinine rise was lower in volunteers compared with the transplant patient, consistent with the concept of renal functional reserve. Our case highlights the importance of taking dietary changes into account when interpreting serum creatinine as a measure of allograft function.

Background Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise training programs in solid organ recipients. Methods We systematically reviewed all randomized controlled trials (RCTs) comparing the outcomes of exercise training programs in solid organ recipients against standard care. MEDLINE, EMBASE, the Transplant Library from the Centre for Evidence in Transplantation, and the Cochrane Central Register of Controlled Trials were searched to June 2012. Results In total, 15 eligible RCTs involving 643 patients (9 cardiac transplants [n=250 patients], 2 kidney transplants [n=164 patients], 3 lung transplants [n=110 patients], and 1 liver transplant [n=119 patients]) were included. Cardiac transplant recipients who engaged in an exercise program after transplantation showed significant improvement in maximal oxygen uptake (standardized mean difference, 0.77; 95% confidence interval, 0.10-1.45) but no improvement in the overall serum lipid profile, blood pressure, and glycemic control compared with standard care. Among other solid organ transplant recipients, no significant improvements in exercise capacity or cardiovascular risk factors such as incidence of new-onset diabetes after transplantation were observed, but all effect estimates were very imprecise. Conclusions Exercise training is a promising but unproven intervention for improving the cardiovascular outcomes of solid organ transplant recipients. Existing trials are small, of relatively short duration, and focused on surrogate outcomes. Large-scale RCTs are urgently required if resources are to be directed toward exercise programs.

Background To date, incidence data for kidney failure in Australia have been available for only those who start renal replacement therapy (RRT). Information about the total incidence of kidney failure, including non–RRT-treated cases, is important to help understand the burden of kidney failure in the community and the characteristics of patients who die without receiving treatment. Study Design Data linkage study of national observational data sets. Setting & Participants All incident treated cases recorded in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) probabilistically linked to incident untreated kidney failure cases derived from national death registration data for 2003-2007. Predictor Age, sex, and year. Outcomes Kidney failure, a combination of incident RRT or death attributed to kidney failure (without RRT). Measurements Total incidence of kidney failure (treated and untreated) and treatment rates. Results There were 21,370 incident cases of kidney failure in 2003-2007. The incidence rate was 20.9/100,000 population (95% CI, 18.3-24.0) and was significantly higher among older people and males (26.1/100,000 population; 95% CI, 22.5-30.0) compared with females (17.0/100,000 population; 95% CI, 14.9-19.2). There were similars number of treated (10,949) and untreated (10,421) cases, but treatment rates were influenced highly by age. More than 90% of cases in all age groups between 5 and 60 years were treated, but this percentage decreased sharply for older people; only 4% of cases in persons 85 years or older were treated (ORs for no treatment of 115 [95% CI, 118-204] for men ≥80 years and 400 [95% CI, 301-531] for women ≥80 years compared with women who were Limitations Cross-sectional design, reliance on accurate coding of kidney failure in death registration data. Conclusions Almost all Australians who develop kidney failure at younger than 60 years receive RRT, but treatment rates decrease substantially above that age.

Aim Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function. Methods Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia. Seventy-five patients were randomized to receive either usual exposure (n = 33) or reduced exposure (n = 42) CsA, EC-MPS 720 mg twice daily, basiliximab and corticosteroids. Results There was no significant difference in mean Cockcroft-Gault CrCl (creatinine clearance) (60.2 ± 17.6 mL/min per 1.73 m2 vs 63.2 ± 24.3, P = 0.64 for usual versus reduced exposure respectively) at 6 months. There was no significant difference between treatment groups in the incidence of treatment failure defined as biopsy proven acute rejection, graft loss or death (secondary endpoint: 30.3% full exposure vs 35.7% reduced exposure). At 12 months the incidence of overall adverse events was the same in both groups. Conclusion This exploratory study suggests de novo renal transplant patients can safely receive a treatment regimen of either full or reduced exposure CsA in combination with EC-MPS, corticosteroids and basiliximab, with no apparent difference in efficacy or graft function during the first year after transplant.