Effects of Allopurinol on the Progression of Chronic Kidney Disease.

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 m2 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 m2; 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 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 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.).

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

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.

Predictors of Change in Left-Ventricular Structure and Function in a Trial of Extended Hours Hemodialysis.

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.

No evidence of a legacy effect on survival following randomization to extended hours dialysis in the ACTIVE Dialysis trial.

AIM: Extended hours haemodialysis is associated with superior survival to standard hours. However, residual confounding limits the interpretation of this observation. We aimed to determine the effect of a period of extended hours dialysis on long-term survival among participants in the ACTIVE Dialysis trial. METHODS: Two-hundred maintenance haemodialysis recipients were randomized to extended hours dialysis (median 24 h/wk) or standard hours dialysis (median 12 h/wk) for 12 months. Further pre-specified observational follow up occurred at 24, 36 and 60 months. Vital status and modality of renal replacement therapy were ascertained. RESULTS: Over the 5 years, 38 participants died, 30 received a renal transplant, and 6 were lost to follow up. Total weekly dialysis hours did not differ between standard and extended groups during the follow-up period (14.1 hours [95%CI 13.4-14.8] vs 14.8 hours [95%CI 14.1-15.6]; P = .16). There was no difference in all-cause mortality (hazard ratio for extended hours 0.91 [95%CI 0.48-1.72]; P = .77). Similar results were obtained after censoring participants at transplantation, and after adjusting for potential confounding variables. Subgroup analysis did not reveal differences in treatment effect by region, dialysis setting or vintage (P-interaction .51, .54, .12, respectively). CONCLUSION: Twelve months of extended hours dialysis did not improve long-term survival nor affect dialysis hours after the intervention period. An urgent need remains to further define the optimal dialysis intensity across the broad range of dialysis recipients.

Kidney Health Australia - Caring for Australasians with Renal Impairment guideline recommendations for infection control for haemodialysis units.

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.

Effect of extended hours dialysis on markers of chronic kidney disease-mineral and bone disorder in the ACTIVE Dialysis study.

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.

A Trial of Extending Hemodialysis Hours and Quality of Life.

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/m2; 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).

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis.

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.

Extended high cut-off haemodialysis for myeloma cast nephropathy in Auckland, 2008-2012.

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.

Calciphylaxis Episodes in the Australia and New Zealand Dialysis and Transplant Registry.

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/m2) 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.

Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease.

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.

End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases.

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.

A stop-gain variant in BTNL9 is associated with atherogenic lipid profiles.

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 (ßHDL-C = -1.60 mg/dL, p HDL-C = 7.63 × 10-10; ßTG = 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.

Troponins in acute kidney injury.

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.

Delay in funding of tolvaptan for polycystic kidney disease in Aotearoa New Zealand.

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 Pataka Whaioranga, The Pharmaceutical Management Agency (PHARMAC), these therapies remain unavailable to New Zealanders resulting in an increased burden of disease to individuals and the whanau and financial cost to the health system.

Nephrogenic systemic fibrosis, in patients with end-stage kidney disease on dialysis, in the greater Auckland region, from 2000-2006.

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.

Frailty prevalence in Aotearoa New Zealand haemodialysis patients and its association with hospitalisations.

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 Waitemata 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.

Quality of Life in Caregivers of Patients Randomized to Standard- Versus Extended-Hours Hemodialysis.

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.

Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype.

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.