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Background Diabetes mellitus (DM) is associated with a greater risk of mortality in kidney transplant patients, primarily driven by a greater risk of cardiovascular disease (CVD)-related mortality. However, the associations between diabetes status at time of first allograft loss and mortality on dialysis remain unknown. Methods All patients with failed first kidney allografts transplanted in Australia and New Zealand between 2000 and 2020 were included. The associations between diabetes status at first allograft loss, all-cause and cause-specific mortality were examined using competing risk analyses, separating patients with diabetes into those with pre-transplant DM or post-transplant diabetes mellitus (PTDM). Results Of 3782 patients with a median (IQR) follow-up duration of 2.7 (1.1–5.4) years, 539 (14%) and 390 (10%) patients had pre-transplant DM or developed PTDM, respectively. In the follow-up period, 1336 (35%) patients died, with 424 (32%), 264 (20%) and 199 (15%) deaths attributed to CVD, dialysis withdrawal and infection, respectively. Compared to patients without DM, the adjusted subdistribution HRs (95% CI) for pre-transplant DM and PTDM for all-cause mortality on dialysis were 1.47 (1.17–1.84) and 1.47 (1.23–1.76), respectively; for CVD-related mortality were 0.81 (0.51–1.29) and 1.02 (0.70–1.47), respectively; for infection-related mortality were 1.84 (1.02–3.35) and 2.70 (1.73–4.20), respectively; and for dialysis withdrawal-related mortality were 1.71 (1.05–2.77) and 1.51 (1.02–2.22), respectively. Conclusions Patients with diabetes at the time of kidney allograft loss have a significant survival disadvantage, with the excess mortality risk attributed to infection and dialysis withdrawal. [ABSTRACT FROM AUTHOR]

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. SUMMARY AT A GLANCE: Based on an observational study of 20,604 public hospital patients suffering from acute coronary syndrome and followed by coronary angiography in New Zealand, the risk of death and recurrent cardiovascular events, as well as bleeding was shown to increase, in a stepwise manner, with worsening CKD stages. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The article focuses on the Kidney Health Australia Caring for Australians with Renal Impairment (KHA-CARI) adaptation of the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) guidelines. The article states that the guidelines addressed issues on the care of kidney transplant recipients in New Zealand and Australia and aim to provide a comprehensive listing of treatment recommendations. The methodology for the adaptation and implementation of the guidelines is provided.

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. [ABSTRACT FROM AUTHOR]

Aim: Although proton pump inhibitors (PPI) are usually safe and effective therapeutic agents, serious adverse effects can occur. The aim of the present study was to report and analyse the clinical features of 15 patients with acute interstitial nephritis (AIN) and acute renal failure from PPI that were referred to renal services in Auckland over a period of 3 years. Methods: The clinical presentation, therapeutic drugs, demographic details and renal outcome of the patients were considered. The population at risk and total PPI exposure were able to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all patients, the time-course of drug exposure and improvement of renal function on withdrawal suggested PPI were causal. Results: The median patient age was 78 years. The mean baseline serum creatinine level was 83 µmol/L, peak level 392 µmol/L, and recovery level 139 µmol/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and 12 patients, respectively, where this information was collected (ESR mean 85 mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient years (95% confidence level 2.6–18.7 per 100 000 patient years). Although four patients presented with an acute systemic allergic reaction, 11 were asymptomatic with an insidious development of renal failure. Conclusion: PPI are now the most commonly identified cause of AIN in the Auckland area. Recovery occurs after withdrawal of the drug but is often incomplete. Early diagnosis may be facilitated by clinician awareness of the insidious onset of renal failure, and an elevated erythrocyte sedimentation rate and C-reactive protein. [ABSTRACT FROM AUTHOR]

SUMMARY: There is a high incidence of end-stage renal disease in New Zealand Maori. Reasons for this have not been established. Transforming growth factor-β1 (TGF-β1) is a profibrogenic cytokine, which stimulates the secretion of extracellular matrix components, and has been implicated in the pathogenesis of kidney failure. The aim of this study was to examine TGF-β1 in the serum of haemodialysis patients at our institution, in order to determine whether there was an upregulation of TGF-β1 in Maori. A TGF-β1-specific sandwich enzyme-linked immunosorbant assay was used to measure active TGF-β1 from the sera of 74 haemodialysis patients, and 19 healthy Maori without renal disease, diabetes or hypertension. In addition, clinical and laboratory markers were examined in the haemodialysis patients studied. There was no association between TGF-β1 and ethnicity in the groups studied. Transforming growth factor-β1 protein appeared to be inversely related to age, but was not associated with parameters of survival on dialysis such as serum albumin or measures of dialysis adequacy. Although there was a significantly higher incidence of type II diabetes mellitus in the Maori (P < 0.001) in comparison to European patients, the glycaemic control was comparable between the groups, as were all other laboratory and clinical parameters studied. This is the first study to examine the fibrogenic growth factor TGF-β1 in New Zealand Maori. Thus, an endogenous increase in TGF-β1 in Maori does not appear to be implicated in the increased incidence of end-stage renal disease in this population. [ABSTRACT FROM AUTHOR]

Background: Post transplantation diabetes mellitus (PTDM) is a common and serious complication after renal transplantation with significant morbidity and mortality. Metformin has proven benefits in the general population and might be advantageous in the prevention and management of PTDM.Methods: Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants had an oral glucose tolerance test (OGTT) in the 4-12 weeks post-transplantation; those with IGT were randomised to standard care or standard care and metformin 500 mg twice daily and followed up for 12 months.Results: Seventy eight patients had an OGTT over 24 months, 25 of them had IGT, of those, 19 patients were randomised, giving a feasibility of recruitment of 24.4%. Ten patients were randomised to metformin and 9 patients to standard care. Tolerability and efficacy was similar between the 2 groups with no serious adverse events. There was no difference in secondary outcomes relating to the metabolic profile.Conclusions: The use of metformin post renal transplantation appeared feasible and safe. Larger randomised controlled trials (RCTs) are needed to establish and confirm the efficacy and safety of metformin post renal transplantation.Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12614001171606 . Date of registration 7/11/2014. [ABSTRACT FROM AUTHOR]

SUMMARY: There is a high incidence of end-stage renal disease in New Zealand Maori. Reasons for this have not been established. Transforming growth factor-β1 (TGF-β1) is a profibrogenic cytokine, which stimulates the secretion of extracellular matrix components, and has been implicated in the pathogenesis of kidney failure. The aim of this study was to examine TGF-β1 in the serum of haemodialysis patients at our institution, in order to determine whether there was an upregulation of TGF-β1 in Maori. A TGF-β1-specific sandwich enzyme-linked immunosorbant assay was used to measure active TGF-β1 from the sera of 74 haemodialysis patients, and 19 healthy Maori without renal disease, diabetes or hypertension. In addition, clinical and laboratory markers were examined in the haemodialysis patients studied. There was no association between TGF-β1 and ethnicity in the groups studied. Transforming growth factor-β1 protein appeared to be inversely related to age, but was not associated with parameters of survival on dialysis such as serum albumin or measures of dialysis adequacy. Although there was a significantly higher incidence of type II diabetes mellitus in the Maori (P < 0.001) in comparison to European patients, the glycaemic control was comparable between the groups, as were all other laboratory and clinical parameters studied. This is the first study to examine the fibrogenic growth factor TGF-β1 in New Zealand Maori. Thus, an endogenous increase in TGF-β1 in Maori does not appear to be implicated in the increased incidence of end-stage renal disease in this population. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. Methods: We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft–Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. Results: Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). Conclusions: In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.) N Engl J Med 2010;363:609-19. [ABSTRACT FROM AUTHOR]