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Aim: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody-mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN)., Methods: All death-censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the "most likely" cause assigned., Results: There were 642 death-censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5-39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody-mediated rejection (37.4%) and chronic T-cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody-mediated rejection., Conclusion: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Aims: Guidelines recommend management with an invasive coronary angiogram in acute coronary syndromes (ACS), but most studies excluded patients with advanced chronic kidney disease (CKD). Our aims were to describe, in a comprehensive ACS cohort, the incidence of CKD, coronary angiography utilisation and outcomes, according to CKD stage., Methods: National datasets were used to identify hospitalised ACS patients (2013 to 2018) in the Northern region of New Zealand. CKD stage was obtained from a linked laboratory dataset. Outcomes included all-cause and cause-specific mortality, and non-fatal myocardial infarction, heart failure and stroke., Results: Thirty-eight percent (38%) of the 23,432 ACS patients had CKD stage 3 or higher: 2,403 (10%) had stages 4/5 CKD. Overall 61% received coronary angiography. Compared with normal renal function the adjusted rate of coronary angiography was lower in CKD stage 3b (RR 0.75, 95% confidence intervals [CIs] 0.69, 0.82) and stages 4/5 without dialysis (RR 0.41, 95% CIs 0.36, 0.46), but similar for those on dialysis (RR 0.89, 95% CIs 0.77, 1.02). All-cause mortality (mean follow-up 3.2 years) increased with CKD stage from 8% (normal kidney function) to 69% (stages 4/5 CKD without dialysis). Compared with coronary angiography, the adjusted all-cause and CVD mortality risks were higher in those without coronary angiography, except for those on dialysis, where these risks converged., Conclusions: Invasive management fell below an eGFR of 45 mL/min (≤ stage 3b), and nearly half of all deaths occurred in these patients. Clinical trials are needed to assess the role of invasive management in ACS and advanced CKD., (Copyright © 2023. Published by Elsevier B.V.)

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF., Methods: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488)., Findings: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48)., Interpretation: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation., Funding: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter., Competing Interests: Declaration of interests MGC has received research support from Baxter Healthcare, the manufacturer of Plasma-Lyte 148, via a Baxter Investigator-Initiated Research grant that provided fluids for the BEST-Fluids trial (commercial value of US$36 270). DWJ has received consultancy fees, research grants, speaker's honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from AstraZeneca and AWAK; speaker's honoraria and travel sponsorships from ONO; and travel sponsorships from Amgen. DR, LEH, LAV, EMP, CK, and JV are employees of the sponsor, The University of Queensland. KBD's salary was funded by a Better Evidence and Translation in Chronic Kidney Disease (BEAT-CKD) grant' and she is an employee of the ANZDATA Registry. PAC is the Deputy Executive Officer of the ANZDATA Registry. CMH has received fees for research committee activities from Janssen and GlaxoSmithKline paid to her institution; personal fees from Otsuka; research grants from Fresenius, Shire, and PKD Australia outside the submitted work; and research grants from Baxter and the National Health and Medical Research Council of Australia related to the current project. LW works in the Department of Anaesthesia at Austin Health, which has received funding from Baxter Healthcare for investigator-initiated clinical research. PFM has received honoraria for presentations on behalf of AstraZeneca and consultancy fees from Vifor. LW has received honoraria from Baxter Healthcare for consulting activities. All LW's fluid-related research, including study design, execution, data collection, analysis, and reporting, has been conducted independently of Baxter Healthcare and other commercial entities. ZHE has received consultancy fees and travel sponsorships from AstraZeneca. WHL has received honoraria from Alexion and education or research grants from Astellas. SJC has received research support, travel support, speaker fees, or honoraria from AstraZeneca, Bayer, CSL-Behring, Novartis, and Takeda. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail., Methods: We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients., Results: During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences., Conclusions: BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide., Competing Interests: M.G.C. has received research support from Baxter Healthcare Pty Ltd, the manufacturer of Plasma-Lyte 148, through a Baxter Investigator-Initiated Research grant that provided fluids for the BEST-Fluids trial (commercial value of US $36 270). D.W.J. has received consultancy fees, research grants, speaker’s honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from AstraZeneca and AWAK; speaker’s honoraria and travel sponsorships from ONO; and travel sponsorships from Amgen. D.R., L.E.H. L.A.V., E.M.P., C.K., and J.V. are employees of the sponsor, The University of Queensland. K.B.D.’s salary was funded by a BEAT-CKD grant‚ and she is an employee of the ANZDATA Registry. P.A.C. is the deputy executive officer of the ANZDATA Registry. C.M.H. has received fees for research committee activities from Janssen and GlaxoSmithKline paid to her institution; personal fees from Otsuka; research grants from Fresenius, Shire, and PKD Australia outside the submitted work; and research grants from Baxter and NHMRC related to the current project. L.W. works in the Department of Anaesthesia at Austin Health, which has received funding from Baxter Healthcare for investigator-initiated clinical research. L.W. has received honoraria from Baxter Healthcare for consulting activities. All L.W.’s fluid-related research, including study design, execution, data collection, analysis, and reporting, has been conducted independently of Baxter Healthcare and other commercial entities. Z.H.E. has received consultancy fees and travel sponsorships from AstraZeneca. W.H.L. has received honoraria from Alexion and education/research grants from Astellas. S.J.C. has received research support, travel support, speaker fees, or honoraria from AstraZeneca, Bayer, CSL-Behring, Novartis, and Takeda. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (<30 ml/min/1.73 m 2 ) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38-2.95] compared to eGFR of 30-60 ml/min/1.73 m 2 ; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m 2 ) was 0.67 [0.62-0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups ( p < 0.01). Recipients with eGFR <30 ml/min/1.73 m 2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m 2 , and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lim, Ooi, Pilmore, Johnson, McDonald, Clayton, Hawley, Mulley, Francis, Collins, Jaques, Larkins, Davies, Wyburn, Chadban and Wong.)

Aims: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). We examined the characteristics, management and outcomes of patients with CKD in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) national registry., Methods: The cohort comprised New Zealand (NZ) patients with an acute coronary syndrome undergoing coronary angiography between January 2013 and December 2016. Patients were categorized according to their stage of CKD. Outcomes included all-cause and cause-specific mortality and hospitalization with myocardial infarction (MI), stroke and major bleeding., Results: Of the 20 604 patients, 20.3% had normal renal function, with 53.3%, 23.3%, 1.7% and 1.4% having CKD stages 2, 3, 4 and 5 CKD, respectively. Patients with severe CKD were more likely to be Māori or Pacific and live in an area with greater socioeconomic deprivation. Death, recurrent MI or stroke, and major bleeding all increased incrementally with each worsening stage of CKD severity. Compared with those with normal renal function, patients with stage 5 CKD had a much higher all-cause (hazard ratio [HR] 16.41, 95% CI 13.06-20.61), cardiovascular (HR 16.38, 95% CI 12.17-22.04) and non-cardiovascular mortality (HR 13.66 9, 95% CI.56-19.51). In addition, patients with stage 5 CKD were at a higher risk of recurrent MI or stroke (HR 4.73, 95% CI 3.86-5.80) and bleeding (HR 5.84, 95% CI 4.39-7.76)., Conclusion: CKD was associated with increased mortality and a high incidence of morbidity in patients undergoing coronary angiography in New Zealand. Initiatives to understand and improve outcomes in this group of patients are urgently needed., (© 2020 Asian Pacific Society of Nephrology.)

Competing Interests: The authors declare no conflicts of interest.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence. The strengths of recommendations are provided in the full report. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, and immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence, and the strengths of recommendations are provided. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.

Background: This is a synopsis of the registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/., Methods: We report data for all solid organ pancreas transplant activity from inception in 1984 to end 2017. Islet-cell transplantation activity is reported elsewhere. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX)., Results: From 1984 to 2017 a total of 809 solid organ pancreas transplants have been performed in Australia and New Zealand, in 790 individuals. In 2017, 52 people received a pancreas transplant. By center, this was; Auckland (4), Monash (17), and Westmead (31). In 2017, 51 transplants were simultaneous pancreas kidney, whereas 1 was pancreas after kidney, and none were pancreas transplant alone., Conclusions: The number of pancreas transplants performed in Australia and New Zealand was slightly lower in 2017 but continues to increase over time., Competing Interests: The authors declare no conflicts of interest.

People with biopsy-proven glomerulonephritis (GN) as their cause of end-stage kidney disease (ESKD) who undergo kidney transplantation incur significant risk of recurrent GN-related graft failure, but the risk in recipients with ESKD where GN was suspected but not biopsy proven (presumed/advanced GN) and when the cause of ESKD is unknown remains uncertain. Using the Australia and New Zealand Dialysis and Transplant registry, we examined the associations between primary kidney transplant recipients whose ESKD was attributed to: 1) commonly-recurring GN (i.e. IgA nephropathy, membranoproliferative GN, focal segmental glomerulosclerosis and membranous GN), 2) presumed/advanced GN, and 3) cause of ESKD unknown (uESKD) and GN-related graft failure using adjusted competing risk models. Of 5258 recipients followed for a median of 8 years, 3539 (67.3%) had commonly-recurring GN, 1195 (22.7%) presumed/advanced GN, and 524 (10.0%) uESKD. Compared to recipients with commonly-recurring GN, recipients with presumed/advanced GN or uESKD experienced a low incidence of GN-related graft failure (<1%) and a lower hazard of GN-related graft failure (adjusted sub-distribution hazard ratio [HR] 0.28 [95%CI 0.15-0.54,p < 0.001] and 0.20 [95%CI 0.06-0.64,p = 0.007], respectively). People with ESKD attributed to either presumed/advanced GN or unknown cause face a very low risk of graft failure secondary to GN recurrence after transplantation.

Background/aims: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients., Methods: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline., Results: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers., Conclusions: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: Overall survival for younger patients with type 2 diabetes without kidney disease has improved substantially over time, but whether a similar pattern of improvement is observed in diabetic kidney transplant recipients remained uncertain. We aimed to compare patient outcomes between diabetic and non-diabetic transplant recipients, and to determine the effect of age and era on patient survival., Methods: This population cohort study included all primary kidney-only transplant recipients included in the Australia and New Zealand Dialysis and Transplant registry between Jan 1, 1994, and Dec 31, 2012. The primary outcomes were all-cause mortality and death with functioning graft. Associations between outcomes and diabetes status were examined using adjusted Cox regression, and interactions between diabetes status and transplant era and recipient age were examined., Findings: Of 10 714 transplant recipients, 985 (9%) had type 2 diabetes. Mortality rates in the first 10 years after transplantation were higher in recipients with diabetes (25·3 per 100 recipients) compared to those without diabetes (11·5 per 100 recipients). Compared with recipients without diabetes, the adjusted hazard ratios (HR) for all-cause mortality and death with a functioning graft in recipients with diabetes were 1·60 (95% CI 1·37-1·86; p<0·0001) and 1·54 (1·28-1·85 p<0·0001), respectively. The association between diabetes status, all-cause mortality, and death with a functioning graft was modified by recipient age (p interaction <0·0001), with the highest risk in recipients with diabetes aged younger than 40 years (adjusted HR 5·16 [95% CI 2·84-9·35], p<0·0001; and 9·83 [4·51-21·43], p<0·0001; for all-cause mortality and death with a functioning graft, respectively). Risk was increased to a lesser extent in recipients with diabetes aged older than 55 years (adjusted HR 1·41 [95% CI 1·17-1·71; p=0·002] and 1·27 [1·02-1·59; p=0·03], for all-cause mortality and death with a functioning graft, respectively). Transplant era did not modify the association between diabetes status and mortality., Interpretation: Kidney transplant recipients with type 2 diabetes had substantially poorer patient survival, with 5-year mortality rates exceeding those for non-diabetic recipients by over two times. The magnitude of this survival disadvantage was greatest in recipients with diabetes aged less than 40 years. By contrast with the general population, there was no evidence of improvement in mortality over time among people with type 2 diabetes following kidney transplantation., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To evaluate incidence, risk factors and treatment outcome of BK polyomavirus nephropathy (BKVN) in a cohort of renal transplant recipients in the Auckland region without a formal BK polyomavirus (BKV) surveillance programme., Methods: A cohort of 226 patients who received their renal transplants from 2006 to 2012 was retrospectively reviewed., Results: Seventy-six recipients (33.6%) had a BK viral load (BKVL) test and 9 patients (3.9%) developed BKVN. Cold ischaemia time (HR = 1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had graft failure from BKVN. BKVN has a negative impact on graft function [median estimated glomerular filtration rate (eGFR) 22.5 (IQR 18.5-53.0) mL/min per 1.73 m 2 , P = 0.015), but no statistically significant difference ( P = 0.374) in renal allograft function was found among negative BK viraemia group [median eGFR 60.0 (IQR 48.5-74.2) mL/min per 1.73 m 2 ), positive BK viraemia without BKVN group [median eGFR 55.0 (IQR 47.0-76.0) mL/min per 1.73 m 2 ] and unknown BKV status group [median eGFR 54.0 (IQR 43.8-71.0) mL/min per 1.73 m 2 ]. The incidence and treatment outcomes of BKVN were similar to some centres with BKV surveillance programmes., Conclusion: Recipients with BVKN have poorer graft function. Although active surveillance for BKV has been shown to be effective in reducing incidence of BKVN, it should be tailored specifically to that transplant centre based on its epidemiology and outcomes of BKVN, particularly in centres with limited resources., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest in the publication of this paper.

Background: β-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT)., Study Design: Pilot RCT., Setting & Participants: Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants., Intervention: After a 6-week run-in with the β-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months., Outcomes & Measurements: The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH)., Results: Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P=0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P=0.7)., Limitations: Unable to recruit planned sample size., Conclusions: Recruiting patients receiving dialysis to an RCT of β-blocker versus placebo will prove challenging. Possible solutions include international collaboration and exploring novel trial designs such as a registry-based RCT., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: Due to the paucity of studies focusing on primary glomerulonephritis, the second commonest cause of end-stage-kidney-disease in most of the developed world, we sought to review outcomes of these renal pathologies., Methods: We reviewed renal outcomes and mortality for primary glomerulonephritis patients enrolled in the New Zealand Glomerulonephritis Study between 1972 and 1983., Results: There were 765 patients with median follow-up of 30 years (range 0.1-42 years). They were predominantly New Zealand European, male and hypertensive. Poor renal outcomes and increased mortality were associated with hypertension, heavy proteinuria, impaired renal function and older age at diagnosis. Ethnicity was not significantly associated with progression to end-stage-kidney-disease although NZ Maori patients were at significantly increased risk of death. Patients with rapidly progressive glomerulonephritis had the highest risk of reaching end-stage-kidney-disease while the cumulative incidence of end-stage-kidney-disease was 20% and 30% for those with immunoglobulin-A nephropathy and membranous nephropathy respectively. Mortality risk was high for patients with rapidly progressive glomerulonephritis and anti-glomerular basement membrane disease. The era of diagnosis did not have much effect on outcomes except for patients with focal segmental glomerulosclerosis or immunoglobulin A nephropathy but this could be type II error., Conclusion: We report one of the longest follow-up studies on biopsy-proven glomerulonephritides. Age, hypertension, and severity of chronic kidney disease at diagnosis were strong predictors of the development of end-stage-kidney-disease and death. The specific renal pathology had a profound impact upon prognosis and therefore should continue to drive efforts to find targeted therapeutic options for these glomerulonephritides., (© 2015 Asian Pacific Society of Nephrology.)

Aims: The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study aims to determine the feasibility of a large-scale randomized controlled trial with clinical endpoints comparing the beta-blocking agent carvedilol with placebo in patients receiving dialysis., Methods: The BLOCADE Feasibility Study is a randomized, double-blind, placebo-controlled, parallel group feasibility study comparing the beta-blocking agent carvedilol with placebo. Patients receiving dialysis for ≥3 months and who are aged ≥50 years, or who are ≥18 years and have diabetes or cardiovascular disease, were eligible. The primary outcome was the proportion of participants who complete a 6-week run-in phase in which all participants received carvedilol titrated from 3.125 mg twice daily to 6.25 mg twice daily. Other measures included how many patients are screened, the proportion recruited, the overall recruitment rate, the proportion of participants who remain on study drug for 12 months and the incidence of intra-dialytic hypotension while on randomized treatment., Results: The BLOCADE Feasibility Study commenced recruiting in May 2011 and involves 11 sites in Australia and New Zealand., Conclusions: The BLOCADE Feasibility Study will inform the design of a larger clinical endpoint study to determine whether beta-blocking agents provide benefit to patients receiving dialysis, and define whether such a study is feasible., (© 2014 Asian Pacific Society of Nephrology.)

Background: Left ventricular function predicts cardiovascular mortality both in the general population and those with end-stage renal disease. Echocardiography is commonly undertaken as a screening test before kidney transplantation; however, there are little data on its predictive power., Methods: This was a retrospective review of patients assessed for renal transplantation from 2000 to 2009. A survival analysis using demographic and echocardiographic variables was undertaken using the Cox proportional hazards regression model., Results: Of 862 patients assessed for transplantation, 739 had an echocardiogram and 217 of 739 (29%) died during a mean follow-up of 4.2 years. In a multivariate survival analysis, increased age (P<0.0001), diabetes (P<0.0001), transplant listing status (P<0.0001), severely impaired left ventricular function (P<0.01), pulmonary hypertension and/or right ventricular dysfunction (P=0.01), and regional wall motion abnormalities (P<0.01) were associated with all-cause mortality. Combined in a score where one point was given for the presence of each of the parameters above, these factors were strongly predictive of increased mortality with a hazard ratio of 3.57, 6.80, and 44.47 for the presence of one, two, or more factors, respectively, compared with the absence of any of these factors., Conclusions: In patients with end-stage renal disease, multiple easily determined echocardiographic parameters, including regional wall motion abnormalities and pulmonary hypertension and/or right ventricular dysfunction, were independently associated with all-cause and cardiovascular mortality. Combining these factors in a simple score may further assist in risk stratifying patients being considered for renal transplantation.

The association between blood pressure and cardiovascular outcomes in patients undergoing hemodialysis remains controversial. This may relate in part to the technique and device used and the timing of the blood pressure measurement in relation to the hemodialysis procedure. Emerging evidence indicates that standardized hemodialysis unit blood pressure measurements or measurements obtained at home, either by the patient or using an ambulatory blood pressure monitor, may offer advantages over routine hemodialysis unit blood pressure measurements for determining cardiovascular risk and treatment. This review discusses the available evidence and implications for clinicians and clinical trials., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

It is reasonable to transplant HbsAg-positive kidneys into recipients who are themselves hepatitis B surface antigen (HbsAg) positive with appropriate antiviral treatment after transplantation. Although there are limited data regarding the hepatitis B virus (HBV) transmission risk following transplantation of kidneys from HbsAg-positive donors into HBV-immune recipients, current literature suggests that the risk of chronic infection in the recipient can be prevented by using antiviral agents or by boosting protective anti-HBs titers. The risk of chronic HBV infection following transplantation of kidneys from HbsAg-positive donors for HBV-naive recipients is high but can be minimized by administering lifelong antiviral therapy. Such a policy could be considered in an urgent situation. The most cost-effective antiviral prophylaxis strategy is lifelong lamivudine. Kidneys from HBsAg neg/anti-HBcore pos recipients are associated with a low rate of chronic HBV infection in the recipient and therefore can no longer be regarded as marginal donors. Booster vaccination to achieve protective HBV immunity or lifelong lamivudine therapy should prevent posttransplant HBV infection. Hence, we believe that strategies allowing transplantation of kidneys from donors with HBV can be undertaken safely with careful selection and matching of donors and recipients increasing access to kidney transplantation.

Background: Cardiovascular disease (CVD) is the most common cause of death after kidney transplantation. Nevertheless, the use of potentially protective CVD medications has not been examined in a large international cohort of kidney transplant patients., Methods: Using the Patient Outcomes in Renal Transplantation database, we retrospectively examined CVD medication use in 14,236 kidney transplant patients from 10 centers worldwide at 4 and 12 months posttransplant., Results: Use of CVD medications posttransplant increased between 1990 to 1994 and 2000 to 2006, with a 12-fold increase in the use of statins (odds ratio [OR] 12.28, 95% confidence interval [CI] 10.18-14.80). Use of β-blockers also increased (OR 3.74, 95% CI 3.20-4.38), as did use of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (OR 3.68, 95% CI 3.07-4.40) and antiplatelet agents (OR 1.93, 95% CI 1.66-2.24). Use of most CVD medications was not higher in patients with diabetes than in patients without diabetes, despite a higher risk of CVD among patients with diabetes. Although use of several CVD medications was higher in patients with previous CVD events than in patients with no previous CVD, less than 75% of patients with previous CVD were using a statin or antiplatelet agent., Conclusion: Although use of CVD medications after kidney transplant has increased in recent years, use of potentially cardioprotective medications may be suboptimal given the high CVD risk in kidney transplant patients.

Diabetes mellitus is the commonest cause of end-stage renal failure in both Australia and New Zealand. In addition, the burden of diabetes is prominent in those with chronic kidney disease who have not yet reached the requirement for renal replacement therapy. While diabetes is associated with a higher incidence of mortality and morbidity in all populations studied with kidney disease, little is known about optimal treatment strategies for hyperglycaemia and the effects of glycaemic treatment in this large group of patients. Metformin is recommended as the drug of first choice in patients diagnosed with type 2 diabetes in the USA, Europe and Australia. There are potential survival benefits associated with the use of metformin in additional to recent studies suggesting benefits in respect to cardiovascular outcomes and metabolic parameters. The use of metformin has been limited in patients with renal disease because of the perceived risk of lactic acidosis; however, it is likely that use of this drug would be beneficial in many with chronic kidney disease. Thus the potential benefits and harms of metformin are outlined in this review with suggestions for its clinical use in those with kidney disease.

Cardiovascular events are markedly elevated in those with all degrees of renal impairment compared to the general population. There are well established guidelines in the general population for the management of coronary artery disease, however, similar guidelines have not been established in the renal population. This review examines the current published work on the detection of coronary artery stenoses in addition to summarizing the outcomes of revascularization in patients with kidney disease. Testing for coronary artery disease in the renal population most commonly occurs in dialysis patients as part of their assessment for renal transplantation. While a positive myocardial stress test for the detection of significant coronary artery stenoses is associated with an increased risk of cardiac events, there is no clear information currently showing that cardiovascular testing itself reduces the rate of adverse cardiac events after transplantation. Revascularization of coronary artery stenoses is associated with higher morbidity and mortality in all groups with kidney disease than in the general population, with the exception of renal transplant recipients where the mortality is likely to be similar to that of the general population. There appears to be a benefit in coronary artery bypass surgery compared to percutaneous intervention in those on dialysis and after renal transplant. Currently, there is little data to support coronary artery intervention prior to transplantation in those with asymptomatic coronary artery disease.

Epithelial-to-mesenchymal transition (EMT) of renal proximal tubular epithelial cells (PTEC) into myofibroblasts is an important step in the pathogenesis of chronic allograft nephropathy. The effects of commonly used immunosuppressives in renal transplantation on EMT are not known. PTEC were cultured in transforming growth factor-beta to induce EMT. The effects of the immunosuppressives on cell morphology and alpha-smooth muscle actin were studied by phase contrast microscopy, immunocytochemistry, and western blotting. The effects on versican were studied by [S] labeling and polyacrylamide gel electrophoresis. Rapamycin and mycophenolate mofetil (MMF) prevented EMT and moreover returned myofibroblasts to PTEC morphology. These immunosuppressives also reduced versican production by both PTEC and myofibroblasts. Cyclosporine A, azathioprine, and methylprednisolone were less effective than rapamycin and MMF. Moreover, these immunosuppressives did not decrease versican. Rapamycin and MMF have a greater inhibitory effect on EMT in vitro than older immunosuppressives and may result in less fibrosis and a better long-term allograft survival.

Aim: Chronic allograft nephropathy is a predictor of poor allograft survival. Protocol and diagnostic biopsies were used to identify markers contributing to its pathogenesis., Methods: Diagnostic, 3- and 12-month protocol biopsies in renal transplant recipients were examined. Immunohistochemical staining with monoclonal antibodies for memory T cells (CD45RO), macrophages (CD68) and alpha smooth muscle actin was undertaken on protocol biopsies., Results: Protocol biopsies revealed the incidence of chronic allograft nephropathy to be 10.7% (3/28) at 3 and 57.6% (19/33) at 12 months. There was a trend towards a higher serum creatinine in patients with chronic allograft nephropathy compared with those without (0.15 +/- 0.04 vs 0.12 +/- 0.04 mmol/L, P = 0.047). The strongest predictor of chronic allograft nephropathy at 12 months was the presence of arteriolar hyaline change (P = 0.035; odds ratio 1.22, 95% CI 0.036-0.887) whereas a higher CD45RO and CD68 count at 12 months was associated with chronic allograft nephropathy (74.7 +/- 56.9 cells/mm(2) and 22.4 +/- 23.5 cells/mm(2)) compared with patients without it (29.2 +/- 29.2 cells/mm(2) and 8.3 +/- 9.9 cells/mm(2), P = 0.006 and P = 0.03, respectively). The number of smooth muscle actin positive cells correlated significantly with chronic allograft nephropathy at 12 month (107.6 +/- 44 vs 73.9 +/- 20.8 cells/mm(2), P = 0.009)., Conclusion: The high prevalence of chronic allograft nephropathy in renal transplant recipients is associated with renal dysfunction. Arteriolar hyalinosis was the most significant predictor at 12 months. There was a significantly higher macrophage and T cell infiltrate in stable grafts undergoing chronic allograft nephropathy at 12 months post transplant.

Background: Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis., Methods: We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively., Results: In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate., Conclusions: In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.

Background: Calcineurin inhibitors (CNI) have significantly reduced the incidence of acute rejection. Nephrotoxicity however, may contribute to long-term allograft dysfunction., Methods: Forty-six biopsies from patients who had been transplanted for more than 6 months were examined. Sixteen biopsies had evidence of chronic allograft nephropathy (CAN) alone, 21 biopsies had evidence of coexisting CAN in addition to histological evidence of calcineurin inhibitor nephrotoxicity (CNIN) while nine had neither evidence of nephrotoxicity nor CAN. Patients with evidence of nephrotoxicity underwent a reduction in dose of CNI while those with CAN alone had no change in therapy. Renal function was followed for a mean of 17.4 months after biopsy., Results: The serum creatinine at the time of diagnostic renal biopsy was comparable between those with CAN alone (mean 0.25 +/- 0.18 mmol/L) and those with coexisting CNIN (mean 0.23 +/- 0.05 mmol/L, p=0.33). The patients with CNIN however, had a rapid improvement in renal function within 1 month after dose reduction. This was sustained for the duration of follow-up (mean serum creatinine 0.162 +/- 0.038 mmol/L at 1 yr after dose reduction; p=0.001). In comparison, those with CAN alone had a gradual decline in renal function with a serum creatinine at 1 yr after biopsy of 0.31 +/- 0.187, p=0.01., Conclusion: Reduction in the dose of CNI in those with histological evidence of nephrotoxicity resulted in a sustained improvement in renal function.

Background: Growth arrest-specific gene 6 (Gas6) is involved in a number of cell functions that include proliferation of vascular smooth muscle cells and mesangial cells. The proliferation of these cells is a feature of chronic rejection (CR) after kidney transplantation. Therefore, we examined the gene expression of Gas6 and its receptors Rse, Axl, and Mer in a rat model of CR., Methods: The rat model of CR was established in Lewis rat recipients of Fisher kidney transplants. The level of mRNA was measured by real-time quantitative reverse transcription-polymerase chain reaction. The proteins were detected by immunohistochemical staining and Western blot analysis., Results: Gas6 mRNA was extensively expressed in kidney tissue of both allografts and isografts. There was significant increase in expression of Gas6 mRNA in allografts at 4 weeks posttransplantation. Immunohistochemical study showed that Gas6 and its receptor Rse proteins were highly expressed in kidney tissue. Western blot analysis has also confirmed that Gas6 and Rse proteins are expressed in kidney tissue., Conclusions: These findings suggest that Gas6 and its receptors have an as yet undefined role in kidney function and/or development and may be involved in the pathogenesis of CR. The action of Gas6 in rat kidney is mainly mediated through the Rse receptors rather than the Axl and Mer receptors.