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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: 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.)

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.)

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.

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.