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Competing Interests: There are no conflicts of interest in the submission of this manuscript. Verbal consent was obtained from the patient for presentation of this case.

Introduction: Calciphylaxis is a rare disorder associated with significant morbidity and mortality. Data registries are an invaluable source of information for rare diseases. We reviewed cases of calciphylaxis recorded in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and evaluated associations and outcomes of this condition., Methods: Data was obtained on all cases of calciphylaxis reported between 2019 and 2022 in Australian and New Zealand patients on kidney replacement therapy (KRT). This cohort was compared to all patients in the registry who received KRT from 2019 to 2022 without an episode of calciphylaxis. Cox proportional hazards regression including a time-varying covariate for calciphylaxis episode was conducted for mortality with models restricted to patients on dialysis only., Results: From 2019 to 2022, 333 patients had calciphylaxis episodes reported. Overall incidence rate for patients on dialysis was 4.5 (4.1-5.1) episodes per 1000 patient-years on dialysis. Median age was 63 (interquartile range [IQR]: 55-73) years, 54% were female, 66% had diabetes, 59% were obese (body mass index [BMI] ≥ 30 kg/m 2 ) and 77% were receiving hemodialysis (HD) treatment. Compared to patients without calciphylaxis ( n  = 46,526), patients with calciphylaxis were more likely to be older, female, and have diabetes, greater BMI, coronary artery, and peripheral vascular disease. The median time to calciphylaxis was 3.2 (IQR: 0.9-6.7) years after KRT commencement. Half of the patients with calciphylaxis died by 12 months from diagnosis. Adjusted hazard ratio (HR) of mortality for patients on dialysis with calciphylaxis <1 year and 1 to 4 years after an episode was 5.8 (4.9-6.9) and 1.5 (1.0-2.1), respectively compared to patients on dialysis without calciphylaxis., Conclusion: Calciphylaxis is a rare but life-threatening condition in people on KRT with the greatest mortality burden within 12 months of diagnosis., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Current understanding of lipid genetics has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history and high prevalence of dyslipidemia may provide insight into the biological foundations of variation in lipid levels. Here, we performed an association study to fine map a suggestive association on 5q35 with high-density lipoprotein cholesterol (HDL-C) seen in Micronesian and Polynesian populations. Fine-mapping analyses in a cohort of 2,851 Samoan adults highlighted an association between a stop-gain variant (rs200884524; c.652C>T, p.R218∗; posterior probability = 0.9987) in BTNL9 and both lower HDL-C and greater triglycerides (TGs). Meta-analysis across this and several other cohorts of Polynesian ancestry from Samoa, American Samoa, and Aotearoa New Zealand confirmed the presence of this association (β HDL-C  = -1.60 mg/dL, p HDL-C  = 7.63 × 10 -10 ; β TG  = 12.00 mg/dL, p TG  = 3.82 × 10 -7 ). While this variant appears to be Polynesian specific, there is also evidence of association from other multiancestry analyses in this region. This work provides evidence of a previously unexplored contributor to the genetic architecture of lipid levels and underscores the importance of genetic analyses in understudied populations., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Autosomal dominant polycystic kidney disease (ADPKD) is the fifth most common cause of end stage kidney disease (ESKD) in Aotearoa New Zealand. Identification of two genes, PCKD1 and PCKD2, which cause the majority of this disease, has played a key role in the development of DNA-sequence molecular diagnostics. ADPKD is characterised by the formation and growth of multiple cysts within the kidney, with some but not all patients progressing to ESKD. The diagnosis of ADPKD is based on the presence of family history, and radiological imaging although increasingly genetic testing is being used for screening and diagnosis. Once diagnosed, standard management of ADPKD includes laboratory monitoring of chronic kidney disease (CKD) parameters, lowering of blood pressure, and a high fluid intake. Over the last decade much research has been undertaken for targeted therapies for ADPKD; however, despite funding of these medications overseas since May 2015, and applications to Te Pātaka Whaioranga, The Pharmaceutical Management Agency (PHARMAC), these therapies remain unavailable to New Zealanders resulting in an increased burden of disease to individuals and the whānau and financial cost to the health system., Competing Interests: Nil., (© PMA.)

Aims: To use two frailty tools to assess frailty prevalence in a cohort of Aotearoa New Zealand haemodialysis (HD) patients and determine factors associated with frailty and frailty's association with adverse health outcomes., Methods: Frailty was measured using the Fried score and Edmonton Frail Scale (EFS) in HD patients dialysing at dependent or satellite clinic sites in Waitematā District Health Board, Auckland. Linear regression models were used to explore factors associated with frailty measurements. Logistic regression models were used to assess associations between frailty and mortality and hospitalisations., Results: 138 participants. Mean (SD) age: 61.5 (13.5) years. 70 females (51%). 51 (37%) were frail by Fried score. 51 (37%) were frail by EFS (overlap of 32 participants). Age, marital status, smoking status and albumin were independently associated with both measures of frailty. Medication number was additionally associated with Fried score. Pacific ethnicity and Charlson Comorbidity Index were associated with EFS score. After adjusting for covariables, only Fried frailty was associated with hospitalisations at six months., Conclusions: Pacific ethnicity was independently associated with increased risk of EFS frailty. Fried frailty was associated with hospitalisations at six months. Given the paucity of literature on the New Zealand population, further work within these ethnic groups is warranted., Competing Interests: Nil.

Introduction: Caregivers are essential for the health, safety, and independence of many patients and incur financial and personal cost in this role, including increased burden and lower quality of life (QOL) compared to the general population. Extended-hours hemodialysis may be the preference of some patients, but little is known about its effects on caregivers., Methods: Forty caregivers of participants of the ACTIVE Dialysis trial, who were randomized to 12 months extended (median 24 hours/wk) or standard (12 hours/wk) hemodialysis, were included. Utility-based QOL was measured by EuroQOL-5 Dimension-3 Level (EQ-5D-3L) and Short Form-6 Dimensions (SF-6D) and health-related QOL (HRQOL) was measured by the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) and the Personal Wellbeing Index (PWI) at enrolment and then every 3 months until the end of the study., Results: At baseline, utility-based QOL and HRQOL were similar in both groups. At follow-up, caregivers of people randomized to extended-hours dialysis experienced a greater decrease in utility-based QOL measured by EQ-5D-3L compared with caregivers of people randomized to standard hours (-0.18±0.30 vs. -0.02±0.16, P  = 0.04). There were no differences between extended- and standard-hours groups in mean change in SF-6D (0.03±0.12 vs. -0.04±0.1, P  = 0.8), PCS (-1.2±9.8 vs. -5.6±9.8, P  = 0.2), MCS (-4.1±11.2 vs. -0.5±7.1, P  = 0.4), and PWI (2.3±17.6 vs. 0.00±20.4, P  = 0.9)., Conclusion: Poorer utility-based QOL, as measured by the EQ-5D-3L, was observed in caregivers of patients receiving extended-hours hemodialysis in this small study. Though the findings are exploratory, the possibility that mode of dialysis delivery negatively impacts on caregivers supports the prioritization of research on burden and impact of service delivery in this population., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

We aimed to generate human induced pluripotent stem cell (iPSC) lines from New Zealand donors. These lines are the first to be generated in New Zealand. Human dermal fibroblasts were collected from two individual donors and reprogrammed with the human OSKM transcription factors using the Sendai virus system. Emerging iPSC colonies were picked, expanded and karyotyped. Clones with normal karyotype were characterised for pluripotency marker expression, p53 mutational status and trilineage differentiation potential. The MANZ-2-2 and MANZ-4-37 iPSC lines showed normal karyotype and expressed pluripotency markers at RNA and protein levels without detectable transgene expression. Both lines differentiated into the three germ layers in vitro and passed the hPSC Scorecard assay for pluripotency and trilineage differentiation. Furthermore, both lines were susceptible to cell apoptosis mediated by nutlin-3a indicative of their wildtype p53 status. This study presents the successful derivation and characterisation of iPSC lines derived from New Zealand donors. These lines will facilitate iPSC-based research in New Zealand and beyond., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Royal Society of New Zealand.)

Background: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known., Methods: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m 2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation., Results: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m 2 ; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m 2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m 2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m 2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group., Conclusions: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Myocardial pathology is common in patients undergoing hemodialysis. To explore the effects of differing aspects of dialysis treatment on its evolution, we examined the impact of change in markers of volume status, hemodynamics and solute clearance on left ventricular (LV) parameters in a randomized trial of extended hours dialysis., Methods and Results: A Clinical Trial of IntensiVE (ACTIVE) Dialysis randomized 200 patients undergoing hemodialysis to extended dialysis hours (≥ 24 hours/week) or standard hours (12-18 hours/week) for 12 months. In a prespecified substudy, 95 participants underwent cardiac magnetic resonance imaging (CMR) at baseline and at the study's end. Generalized linear regression was used to model the relationship between changes in LV parameters and markers of volume status (normalized ultrafiltration rate and total weekly interdialytic weight gain), hemodynamic changes (systolic and diastolic blood pressure) and solute control (urea clearance, dialysis hours and phosphate). Randomization to extended hours dialysis was not associated with change in any CMR parameter. Reduction in ultrafiltration rate was associated with reduction in LV mass index (P = 0.049) and improved ejection fraction (P = 0.024); reduction in systolic blood pressure was also associated with improvement in ejection fraction (P = 0.045); reduction in interdialytic weight gain was associated with reduced stroke volume (P = 0.038). There were no associations between change in urea clearance, phosphate or total hours per week and CMR parameters., Conclusions: Reduction in ultrafiltration rate and blood pressure are associated with improved myocardial parameters in hemodialysis recipients independently of solute clearance or dialysis time. These findings underscore the importance of fluid status and related parameters as potential treatment targets in this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload., Methods: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging., Results: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake., Conclusions: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status., Clinical Trial Registry Name and Registration Number: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998., (Copyright © 2020 by the American Society of Nephrology.)

Background: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis., Methods: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m 2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD)., Results: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups., Conclusions: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.)., (Copyright © 2020 Massachusetts Medical Society.)

Multidrug-resistant organisms cause significant morbidity and mortality. Infections due to resistant gram-negative bacilli are increasingly being reported. For years, carbapenem antibiotics have been successfully used to treat infections due to resistant Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae , including those producing extended spectrum β-lactamases, a subset of β-lactamase enzymes that confer broad resistance to penicillins and cephalosporins. More recently, carbapenem-resistant Enterobacteriaceae have emerged as pathogenic organisms, which confer broad resistance to most β-lactam antibiotics including 'last-line' carbapenems. However, different types of carbapenemases confer diverse spectra of antibiotic resistance. Here, we describe the case of an 84-year-old lady on peritoneal dialysis (PD) for 3 years who, on developing carbapenem-resistant Klebsiella pneumoniae PD peritonitis, was successfully treated with colistin, an antimicrobial agent first used in the 1950s.

Aim: There is no national consensus on infection control in haemodialysis units in Australia and New Zealand. The primary aim of this guideline was to provide recommendations on screening for blood-borne viruses and multi-resistant organisms for dialysis units based on the available evidence., Methods: The Kidney Health Australia Caring for Australasians with Renal Impairment guidelines, overall approach to guideline development follows the GRADE framework. A facilitated workshop was conducted to ensure that patient and caregiver concerns were considered. The evidence from relevant medical databases on the impact of screening on detection and transmission rates, hospitalization, mortality and psychosocial care, was reviewed and critically appraised. The guideline group made recommendations from the evidence available., Results: The main guideline recommendations are: Dialysis units adopt a comprehensive approach that encompasses standard infection control precautions. Conduct routine surveillance for key blood-borne viruses and methicillin-resistant Staphylococcus aureus. Conduct routine surveillance of individual levels of protection against hepatitis B for patients on haemodialysis. Use dedicated dialysis machines for HBV-infected patients. The evidence in totality was not found to support routine surveillance of vancomycin-resistant Enterococci . Enhanced surveillance in light of the local risk of transmittable infectious agents should be considered by dialysis units. Very few studies have reported on the potential adverse effects of screening and associated practices., Conclusions: Future research should focus on the potential benefits and adverse effects of screening and associated practices on clinical outcomes including infections prevented and health service delivery, and psychosocial domains for patients. Given the results of trials in the critical setting, the effectiveness of methicillin-resistant Staphylococcus aureus decolonization in people receiving dialysis therapy warrants further research., (© 2018 Asian Pacific Society of Nephrology.)

Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene-gene interactions to confirm these findings and may allow personalised treatment regimens., (© 2019 The British Pharmacological Society.)

Background: Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups., Methods: The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression., Results: Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home., Conclusion: Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups., Trial Registration: Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.

Background and Objectives: Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients., Design, Setting, Participants, & Measurements: This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses., Results: The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 ( P =0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated ( P <0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up., Conclusions: Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017&#95;11&#95;21&#95;CJASNPodcast&#95;18&#95;1&#95;v.mp3., (Copyright © 2018 by the American Society of Nephrology.)

The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12-15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6-24.0) and 12.0 (interquartile range, 12.0-16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, -0.03 to 0.11]; P =0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, -6.0 [95% confidence interval, -14.8 to 2.7] g/m 2 ; P =0.18). Five deaths occurred in the extended group and two in the standard group ( P =0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298)., (Copyright © 2017 by the American Society of Nephrology.)

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.

Aim: To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis (MALA)., Methods: Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identified using clinical coding. A retrospective case notes review identified patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme., Results: There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 (95%CI: 7.88-21.66) compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular filtration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m(2). Only two patients had chronic kidney disease G4. Three patients required treatment with haemodialysis. Two patients died., Conclusion: Lactic acidosis is an uncommon but significant complication of use of metformin which carries a high risk of morbidity.

After the publication of our paper Dunlop et al. "Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass", we became aware of further data correlating left ventricular (LV) mass index at baseline and their corresponding mass at 12 months, using cardiac magnetic resonance imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson's correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson's correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants.

Background: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it's inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms., Methods/design: The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials that contraindicate the study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will receive dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12 months. The secondary outcomes will be assessed using cardiac magnetic resonance imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass to volume ratio and patterns of LV remodeling at 0 and 12 months., Discussion: The Mac-SoLID study enhances and complements the SoLID trial. It tests whether potential gains in cardiovascular health (reduced LV mass) which low dialysate [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular health through alternative mechanisms, namely repeated LV stunning and micro-injury., Trial Registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.

Myeloma cast nephropathy contributes to high morbidity and early mortality associated with the development of end-stage renal disease. Treatment with extended high cut-off haemodialysis coupled with novel anti-myeloma therapies enables significant reduction of serum-free light chains and has been shown to improve renal outcomes. In this case series, medical records of 6 patients who received high cut-off haemodialysis for biopsy-proven cast nephropathy were retrospectively reviewed. Patients received a total of 344 hours of high cut-off haemodialysis and concurrent chemotherapy. Only 50% became dialysis independent following treatment. One patient who achieved sustained remission remained dialysis dependent. The added benefit of high cut-off haemodialysis in the light of novel anti-myeloma therapies requires further evaluation., (© 2014 Asian Pacific Society of Nephrology.)

Aims: Hepatitis B (HBV) is an important cause of morbidity and mortality in end-stage renal disease patients. The effect of oral antiviral therapy on survival in this population is not known. We evaluated the impact of oral antivirals on survival of HBV-infected haemodialysis patients., Method: This retrospective study included 52 HBsAg-positive haemodialysis patients and 156 non-infected haemodialysis controls. Criteria adopted for starting lamivudine were the 2001 American Association for the Study of Liver Diseases guidelines. Lamivudine was commenced in 21 (40.4%) patients, with median treatment duration of 58 months. The primary endpoint was transplant-free survival., Results: Survival of HBsAg-positive patients was equivalent to that of age- and sex-matched HBsAg-negative controls (39.1% vs 33.2% at 10 years, respectively; P=0.12). In treated patients, complete viral suppression was associated with improved survival (serial HBV DNA less than and equal to 2 log10 IU/mL, 90.9% vs HBV DNA >2 log10 IU/mL on at least one occasion, 74.1% at 5 years; P=0.049). Out of 20 deaths, three were liver-related., Conclusion: Haemodialysis patients with chronic HBV, when given oral antiviral therapy if indicated, had equivalent long-term survival to that of non-infected controls. In those with active viral hepatitis, viral suppression was associated with reduced liver-related mortality.

Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes., Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis., Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events., Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

Background: The Asia Pacific Meeting for Vasculitis and ANCA Workshop was held in Tokyo in May 2012. This review of vasculitis in New Zealand (NZ) was prepared for the meeting., Methods: A review of significant NZ demographic and health data is presented with information from relevant studies on vasculitis originating from NZ., Results: Giant cell arteritis occurs in older adults, and has an annual incidence of 12.7/100,000 adults over the age of 50 years in NZ. Kawasaki disease, a rare cause of acquired cardiac disease primarily affecting young children, has an annual incidence of 8.0/100,000 children aged less than 5 years. The prevalence of granulomatosis with polyangiitis varies within NZ, with a 5-year prevalence varying from 29 to 75 cases per million people. Dual anti-glomerular basement membrane disease and ANCA-associated systemic vasculitis is rare, with an annual incidence estimated at 0.47 cases per million people., Conclusions: Vasculitis is an uncommon but a significant cause of morbidity and mortality in NZ.

Background: The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients., Methods/design: The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point., Discussion: The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients., Trial Registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.

There are few reports regarding outcomes of anti-glomerular basement membrane (GBM) disease in patients who underwent renal replacement therapy. To help define this we studied all patients with anti-GBM disease who started renal replacement therapy for end-stage renal disease (ESRD) in Australia and New Zealand (ANZDATA Registry) between 1963 and 2010 encompassing 449 individuals (0.8 percent of all ESRD patients). The median survival on dialysis was 5.93 years with death predicted by older age and a history of pulmonary hemorrhage. Thirteen patients recovered renal function, although 10 subsequently experienced renal death after a median period of 1.05 years. Of the 224 patients who received their first renal allograft, the 10-year median patient and renal allograft survival rates were 86% and 63%, respectively. Six patients experienced anti-GBM disease recurrence in their allograft, which led to graft failure in two. Using multivariable Cox regression analysis, patients with anti-GBM disease had comparable survival on dialysis or following renal transplantation (hazard ratios of 0.86 and 1.03, respectively) compared to those with ESRD due to other causes. Also, renal allograft survival (hazard ratio of 1.03) was not altered compared to other diseases requiring a renal transplant. Thus, anti-GBM disease was an uncommon cause of ESRD, and not associated with altered risks of dialysis, transplant or first renal allograft survival. Death on dialysis was predicted by older age and a history of pulmonary hemorrhage.

Background: There are few reports regarding the long-term renal replacement therapy (RRT) outcomes of amyloidosis., Methods: In this retrospective, multi-centre, multi-country registry analysis, all patients with and without amyloidosis who commenced RRT for end-stage renal failure (ESRF) in Australia and New Zealand between 1963 and 2010 were included., Results: Of 58 422 patients who underwent RRT during the study period, 490 (0.8%) had ESRF secondary to amyloidosis. The median survival of amyloidosis patients on dialysis (2.09 years, 95% CI 1.85-2.32 years) was significantly inferior to that of patients with other causes of ESRF (4.45 years, 95% CI 4.39-4.51 years) (log-rank score 242, P < 0.001). The survival of amyloidosis patients receiving peritoneal dialysis (1.9 years, 95% CI 1.58-2.22) was comparable with those receiving haemodialysis (2.17 years, 95% CI 1.89-2.45) (P = 0.18). Fifty-three (13.8%) amyloidosis patients died of amyloidosis complications. Forty-six patients underwent renal transplantation with first graft survival rates of 45% at 5 years and 26% at 10 years. Nine (16.4%) patients experienced amyloidosis recurrence in their allografts, which led to graft failure in six patients. ESRF patients with amyloidosis experienced inferior median first renal allograft survival (4.55 years, 95% CI 1.96-7.15 versus 10.7 years, 95% CI 10.5-11.0, P = 0.001) and transplant patient survival (6.03 years, 95% CI 2.71-9.36 versus 16.8 years, 95% CI 16.4-17.1, P < 0.001) compared with patients with other causes of ESRF. Respective 10-year patient survival rates were 37 and 69%., Conclusions: Amyloidosis was associated with poor patient survival following dialysis and/or renal transplantation, poor renal allograft survival and a significant incidence of disease recurrence in the allograft. An appreciable proportion of amyloid ESRF patients died of amyloidosis-related complications.

Background: Anti-glomerular basement membrane (GBM) antibody-mediated disease is rare and classically presents with the syndrome of glomerulonephritis and pulmonary haemorrhage., Aim: This aim of this report was to determine the incidence, clinical features, management and outcomes of anti-GBM disease in Auckland between 1998 and 2008., Methods: Potential patients were identified by a search for positive anti-GBM antibody serology, diagnostic renal biopsy, or in-hospital admissions using International Classification of Diseases 9 and 10 codes between 1998 and 2008. A retrospective case notes review of all potential cases was performed with data censored at 31 December 2010., Results: Twenty-three cases were identified. The rate of anti-GBM disease was estimated at 1.79 per million person-years. There were 12 men and 11 women. The median age was 45 years, range 12-74 years. Sixteen patients were European, three were Pacific peoples, three were NZ Maori and one was Chinese. Eleven were regular smokers and eight ex-smokers, significantly higher proportions than the population (P ≤ 0.001). Smokers were significantly more likely to have respiratory disease (P= 0.03). The mean creatinine at presentation was 474 µmol/L. All patients had a renal biopsy; 20 had crescentic glomerulonephritis. One patient recovered renal function without treatment. Twenty-two were immunosuppressed with cyclophosphamide and corticosteroids. Seventeen received plasmapheresis. Eighteen were alive, eight with end-stage renal disease, two with chronic kidney disease and eight with normal renal function., Conclusions: Anti-GBM disease is a rare condition, which is not overrepresented among indigenous people. With aggressive therapy the prognosis has improved; however, the morbidity and mortality of this condition remain significant., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Aim: To investigate and describe cardiac troponins in subjects with acute kidney injury (AKI)., Methods: A prospective observational study of troponin in subjects presenting with AKI in a tertiary hospital. Creatine kinase-MB (CKMB), troponin I (Abbott Laboratories), and troponin T (Roche 4th generation) were measured. Patients with conditions known to cause elevated troponin levels were excluded., Results: Nineteen subjects were enrolled in the study. Six subjects had troponin I and T concentrations above the 99th percentile of a reference population. There was high concordance of result between troponin I and troponin T. However, the concordance of elevated troponin levels with CKMB was less marked at 45%. Statistically significant factors associated with elevated troponin levels were age over 60 years, abnormal electrocardiogram, and history of previous ischemic heart disease., Conclusion: This is the first study able to demonstrate impaired renal function occurring acutely, without known confounders, results in elevated troponin levels. This suggests that impaired renal function disease influences plasma troponin levels in AKI as well as in chronic kidney failure.

Hypertension is common in patients with end stage renal disease. However, in patients non-responsive to standard measures to control the blood pressure, non-renal causes should be considered. We present the case of a patient on haemodialysis with difficult to control blood pressure.

Aim: Nephrogenic systemic fibrosis (NSF) is a rare and serious disease characterised by thickening and hardening of the skin with fibrosis of the dermis with CD34-positive fibrocytes. NSF occurs in patients with renal failure and has been linked to exposure of gadolinium contrast agents. The Auckland region has a population of 1.3 million with consultation and dialysis services for patients with end stage kidney disease provided by two separate renal units. The aim of this study was to determine the incidence and frequency of NSF in the Auckland region and determine the risk based on exposure to gadolinium based contrast agents., Methods: A retrospective case notes review of all patients with end stage kidney disease under the care of the renal services between 1(st) January 2000 and 31(st) December 2006 was undertaken. All cases of proven or suspected NSF were identified. Using a picture archive and communications support system all imaging and exposure to contrast was identified., Results: Three cases of biopsy proven NSF and two further cases of clinical NSF were identified. In all cases there was exposure to Gadolinium. This risk of NSF on exposure to any gadolinium based contrast agents was 0.67%. Gadodiamide was used in one institution where all five cases of NSF were seen, gadodiamide was used in 1% of patients in the other institution with no recognised cases., Conclusion: The incidence of NSF is low with the greatest risk on exposure to linear, non-ionic chelates, with no ethnic predisposition., (© 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrology.)

Aim: Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN., Methods: Twenty patients were genotyped for the CYP2C19 variant alleles (2, 681G>A and 3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status., Results: The frequency of the CYP2C19 2 allelic variant was 12.5%, no 3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers., Conclusions: There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN.

Background: Peritonitis is a significant source of morbidity and mortality in patients on peritoneal dialysis (PD). Symptoms may persist, requiring an emergency laparotomy. Although increasingly used, we find that, in PD patients, abdominal computerized tomography (CT) is ineffective in determining significant pathology. This study was undertaken to assess the diagnostic utility of CT for the identification of intra-abdominal collections in PD patients presenting with peritonitis., Methods: A retrospective chart review was undertaken of all patients that underwent abdominal CT scanning in the context of severe PD peritonitis in the past 2 years. All of these patients had at least one CT scan preoperatively., Results: 133 patients presented with PD peritonitis; 19 patients had a contrast CT procedure (12 females, 7 males). Average age was 59.2 years; mean duration on PD was 43.8 months. 13 of 19 patients had gram-negative bacillary peritonitis, 6 of whom had polymicrobial peritonitis; 4 patients had fungal peritonitis and 2 had Staphylococcus aureus peritonitis. 26 CT scans were done in 19 patients an average of 10 days after presentation. 21 of 26 scans revealed no collections of surgical interest. 12 laparotomies were performed, with an average delay of 10.4 days from presentation to laparotomy. Of the 12 laparotomies, 6 found a drainable collection not seen on CT. Seven of the 19 patients died (37%) and no patient was able to return to PD., Conclusion: PD patients requiring emergency laparotomy following PD peritonitis have a high mortality rate. A negative abdominal CT in the setting of ongoing symptoms should not be taken as reassuring, nor should it delay proceeding to emergency laparotomy.

The podocyte is a highly specialized cell that plays a key role in regulating the glomerular filtration barrier. A number of advances have been made in recent years, linked to the discovery of single-gene defects in hereditary glomerular disease, which highlight the role of this cell in preventing proteinuria. This article reviews the molecular biology of the podocyte, focusing on known genetic abnormalities.

Cardiovascular disease is the most common cause of death in patients with renal failure. Patients with renal failure are at greater risk of atypical presentations of myocardial ischaemia. Traditional markers of myocardial damage are often increased in renal failure in the absence of clinically suspect myocardial ischaemia. The cardiac troponins are specific markers of myocardial injury. Large-scale trials, excluding patients with renal disease, have shown the importance of the cardiac troponins in predicting adverse outcome and in guiding both therapy and intervention in acute coronary syndromes. Cardiac Troponin T and cardiac Troponin I are increased in patients with renal failure and this is likely to represent multifactorial pathology including cardiac dysfunction, left ventricular hypertrophy and cardiac microinfarctions. Increases in serum troponin from baseline, in patients with renal disease with acute coronary syndromes, may represent a poor prognosis. Small studies of patients with renal failure have suggested that elevation of the cardiac troponins is associated with an increased risk of cardiac death.