The impact of peritoneal dialysis on oxypurinol and urate elimination in people with gout.

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.

Autosomal dominant hypercalciuric hypocalcaemia: the calcium-sensing receptor in renal calcium homeostasis and the impact of renal transplantation.

Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that help maintain Ca2+ concentrations, modulating calciotropic hormone release (parathyroid hormone (PTH), calcitonin and 1,25-dihydroxyvitamin D) by direct actions in the kidneys, gastrointestinal tract and bone. Variability in population calcium levels has been attributed to single nucleotide polymorphisms in CaSR genes, and several conditions affecting calcium and phosphate homeostasis have been attributed to gain- or loss-of-function mutations. An example is autosomal dominant hypercalciuric hypocalcaemia, because of a missense mutation at codon 128 of chromosome 3, as reported in our specific case and her family. As a consequence of treating symptomatic hypocalcaemia as a child, this female subject slowly developed progressive end-stage kidney failure because of nephrocalcinosis and nephrolithiasis. After kidney transplantation, she remains asymptomatic, with decreased vitamin D and elemental calcium requirements, stable fluid and electrolyte homeostasis during intercurrent illnesses and has normalised urinary calcium and phosphate excretion, reducing the likelihood of hypercalciuria-induced graft impairment. We review the actions of the CaSR, its role in regulating renal Ca2+ homeostasis along with the impact of a proven gain-of-function mutation in the CaSR gene resulting in autosomal dominant hypercalciuric hypocalcaemia before and after kidney transplantation.

Health-Related Quality of Life and Disability Among Older New Zealanders With Kidney Failure: A Prospective Study.

Background: Disability is prevalent in individuals with kidney failure and can contribute to significantly reduced quality of life and survival. In older individuals with kidney failure, disability can be caused by a combination of factors, including issues directly related to their kidney disease and/or treatment, including weakness, low energy, and low activity. Few studies have investigated health-related quality of life (HRQoL) as a possible predictor of disability among older individuals experiencing kidney failure. Objective: This study aimed to determine if patient-reported HRQoL, and/or other factors at baseline, predicts disability in people with kidney failure, aged ≥65 years, after 12 months of follow-up. Design: The DOS65+ study was an accelerated longitudinal cohort design comprising of both cross-sectional and longitudinal components. Participants were eligible if they were aged ≥65 years, had chronic kidney disease stage 5G (CKD 5G) (estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2), and had: commenced kidney replacement education, or were on an active conservative pathway, or were newly incident dialysis patients commencing dialysis therapy or prevalent on dialysis. Setting: Three New Zealand District Health Board (DHB) nephrology units (Counties Manukau, Hawke's Bay, and Southern DHB) were involved in the study. Participants: Participants were eligible if they were aged ≥65 years, had CKD 5G (eGFR <15 ml/min/1.73 m2), and had: commenced kidney replacement education, or were on an active conservative pathway, or were newly incident dialysis patients commencing dialysis therapy or prevalent on dialysis. Measurements: Disability and HRQoL were measured by EQ-5D-3L, a WHO Disability Assessment Schedule (WHODAS) 2.0. Methods: Baseline and 12-month data from our longitudinal dialysis outcomes in older New Zealanders' study were analyzed to determine if HRQoL at baseline predicted disability outcomes 12 months later. Results: Of the 223 participants at baseline, 157 participants completed a follow-up interview 12 months later. Individuals with "considerable disability" at baseline had a significantly (86%) higher risk of experiencing "considerable disability" at 12 months compared with those with "lesser/no disability" at baseline. Two thirds of those with ≥3 comorbidities were experiencing "considerable disability." In addition, those with problems with EQ-5D-3L self-care, EQ-5D-3L usual activities, and EQ-5D-3L anxiety/depression reported higher rates of disability. Limitations: Selection bias is likely to have been an issue in this study as participants were excluded from the follow-up interview if they had an intercurrent illness requiring hospitalization within 2 weeks of the survey interview or if the treating nephrologist judged that the individual's ability to take part was significantly impaired. Sample size meant there were a limited number of explanatory/confounding variables that could be investigated in the multivariable model. Conclusions: EQ-5D-3L mobility and self-care may be useful in predicting subsequent disability for individuals with CKD 5G. Although individuals with kidney failure often experience disability, previous studies have not clearly identified HRQoL or disability as predictors of later disability for individuals with kidney failure. Therefore, we would recommend the assessment of mobility and self-care, in conjunction with existing disabilities in the clinical review and pre-dialysis education of individuals with kidney failure as they approach the need for kidney replacement therapy.Trial registration: the Australian and New Zealand clinical trials registry: ACTRN12611000024943.

Renal manifestations of syphilis.

Syphilis is a sexually transmitted disease caused by spirochaete Treponema pallidum. The incidence of syphilis is rising across the globe. It has been described in the literature as a great imitator due to the vast range of clinical manifestations that can occur in the disease. Renal manifestations are rare but a feature of secondary syphilis. It can cause glomerulopathies, tubular pathology and vasculitic lesions in the kidney. Membranous nephropathy is the most commonly reported glomerular lesion associated with syphilis. With two recent cases of secondary membranous nephropathy due to syphilis, it is timely to review the current state of knowledge, and discuss the different renal manifestation of syphilis, its pathology and treatment options.

Predictors of Health Deterioration Among Older New Zealanders Undergoing Dialysis: A Three-Year Accelerated Longitudinal Cohort Study.

BACKGROUND: Patient involvement in dialysis decision-making is crucial, yet little is known about patient-reported outcomes over time on dialysis. OBJECTIVE: To examine health-related outcomes over 24 and 36 months in an older cohort of dialysis patients. DESIGN: The "Dialysis outcomes in those aged ≥65 years study" is a prospective longitudinal cohort study of New Zealanders with kidney failure. SETTING: Three New Zealand nephrology units. PATIENTS: Kidney failure (dialysis and predialysis) patients aged 65 or above. We have previously described outcomes after 12 months of dialysis therapy relative to baseline. MEASUREMENTS: Patient-reported social and health factors using the SF-36, EQ-5D, and Kidney Symptom Score questionnaires. METHODS: This article describes and compares characteristics of 120 older kidney failure patients according to whether they report "Same/better" or "Worse" health 24 and 36 months later, and identifies predictors of "worse health." Modified Poisson regression modeling estimated relative risks (RR) of worse health. RESULTS: Of 120 patients at 12 months, 47.5% had worse health or had died by 24 months. Of those surviving at 24 months (n = 80), 40% had "Worse health" or had died at 36 months. Variables independently associated with reduced risk of "Worse health" (24 months) were as follows: Maori ethnicity (RR = 0.44; 95% CI = 0.26-0.75), Pacific ethnicity (RR = 0.39; 95% CI = 0.33-0.46); greater social satisfaction (RR = 0.57; 95% CI = 0.46-0.7). Variables associated with an increased risk of "Worse health" were as follows: problems with usual activities (RR = 1.32; 95% CI = 1.04-1.37); pain or discomfort (RR = 1.48; 95% CI = 1.34, 1.63). At 36 months, lack of sense of community (RR = 1.41; 95% CI = 1.18-1.69), 2 or more comorbidities (RR = 1.21; 95% CI = 1.13-1.29), and problems with poor health (RR = 1.47; 95% CI = 1.41-1.54) were associated with "Worse health." LIMITATIONS: Participant numbers restricted the number of variables able to be included in the multivariable model, and hence there may have been insufficient power to detect certain associations. CONCLUSIONS: In this study, the majority of older dialyzing patients report "Same/better health" at 24 and 36 months. Maori and Pacific people report better outcomes on dialysis. Social and/or clinical interventions aimed at improving social satisfaction, sense of community, and help with usual activities may impact favorably on the experiences for older dialysis patients. TRIAL REGISTRATION: Australian and New Zealand clinical trials registry: ACTRN12611000024943.

CONTEXTE: La participation des patients à la prise de décisions est essentielle en contexte de traitements de dialyse. On en sait toutefois peu sur les résultats observés par les patients en cours de traitement. OBJECTIF: Examiner les résultats liés à la santé sur une période de 24 et de 36 mois dans une cohorte de patients âgés suivant des traitements de dialyse. TYPE D'ÉTUDE: Cette étude intitulée Dialysis outcomes in those aged ≥65 years est une étude de cohorte prospective et longitudinale menée auprès de Néo-Zélandais atteints d'insuffisance rénale. CADRE: Trois unités de néphrologie en Nouvelle-Zélande. SUJETS: Des patients âgés de plus de 65 ans atteints d'insuffisance rénale (dialyse et prédialyse). Nous avions antérieurement décrit les résultats observés après 12 mois de dialyse par rapport au début de l'étude. MESURES: Les facteurs sociaux et l'état de santé déclarés par les patients par l'entremise des questionnaires SF-36, EQ-5D et Kidney Symptom Score. MÉTHODOLOGIE: Dans cet article, nous décrivons et comparons les caractéristiques de 120 patients âgés atteints d'insuffisance rénale selon qu'ils avaient déclaré un état de santé « inchangé/meilleur ¼ ou « empiré ¼ après 24 et 36 mois. Nous discutons également des facteurs prédictifs d'un état de santé jugé « empiré ¼. Un modèle de régression de Poisson corrigé a servi à estimer le risque relatif (RR) de progresser vers un état de santé « empiré ¼. RÉSULTATS: Des 120 patients évalués après 12 mois, 47,5 % avaient déclaré un état de santé « empiré ¼ ou étaient décédés après 24 mois. Parmi les survivants à 24 mois d'étude (n = 80), 40 % avaient déclaré un état de santé « empiré ¼ ou étaient décédés après 36 mois. Les variables associées de façon indépendante à un risque réduit de voir l'état de santé empiré (24 mois) étaient : le fait d'être Maori (RR = 0,44; IC 95% = 0.26-0.75) ou issu d'une population du Pacifique (RR = 0.39; IC 95% = 0.33-0.46) et une satisfaction sociale plus élevée (RR = 0.57; IC 95% = 0.46-0.7) constituent les variables qui ont été associées de façon indépendante à un risque réduit de voir un état de santé empiré après 24 mois. Parmi les variables associées à un risque accru d'aggravation de l'état de santé, on compte des difficultés à pratiquer les activités quotidiennes (RR = 1.32; IC 95% = 1.04-1.37) et la douleur ou l'inconfort (RR = 1.48; IC 95% = 1.34-1.63). Après 36 mois de traitement, l'absence d'un sentiment de communauté (RR = 1,41; IC 95% = 1.18-1.69), le fait de présenter au moins deux maladies concomitantes (RR = 1.21; IC 95% = 1.13-1.29) et des problèmes liés à une mauvaise santé (RR = 1.47; IC 95% = 1.41-1.54) ont été associés à un état de santé jugé « empiré ¼. LIMITES: Le faible nombre de participants a restreint le nombre de variables pouvant être incluses dans le modèle multivarié, il est donc possible que la puissance de détection de certaines associations soit insuffisante. CONCLUSION: Dans cette étude, la majorité des patients âgés sous dialyse ont déclaré avoir un état de santé « inchangé/meilleur ¼ après 24 et 36 mois de traitement. Les patients Maoris et ceux qui sont originaires du Pacifique ont déclaré de meilleurs résultats de dialyse. Les interventions sociales ou cliniques visant à améliorer la satisfaction sociale, le sentiment d'appartenance à la communauté et l'aide aux activités quotidiennes pourraient avoir un effet bénéfique sur le vécu des patients âgés suivant des traitements de dialyse.

Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease?

This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD). The INH assumes that glomerular filtration rate (GFR) will account for all kidney drug handling even for drugs eliminated by tubular secretion like metformin. We conducted two studies: (1) a regression analysis to explore the relationship between metformin clearance and eGFR metrics, and (2) a joint population pharmacokinetic analysis to test the relationship between metformin renal clearance and gentamicin clearance. The relationship between metformin renal clearance and eGFR metrics and gentamicin clearance was found to be linear, suggesting that a proportional dose reduction based on GFR in patients with CKD is reasonable.

Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15-29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.

Refinement of a protocol to induce reliable muscle cramps in the abductor hallucis.

OBJECTIVE: To test the reliability of immediate replication of muscle cramp characteristics induced with different electrical stimulation protocols. APPROACH: Five (age 33.8 ± 5.7 y, 60% male) and ten (age 47.4 ± 11.7 y, 60% male) participants completed independent discovery and validation cohorts, respectively. This was to identify a protocol that resulted in consistent muscle cramp characteristics (discovery), and to examine the test-retest reliability of the identified protocol (validation). Electrical stimulation (150 burst) at abductor hallucis motor-point was used to induce muscle cramps with 4 Hz increments in stimulation frequency (8-32 Hz) or until muscle cramp was first evident, followed by refinement (2 and 1 Hz) until at least two muscle cramps occurred. This defined the cramp threshold frequency, and concurrent electromyogram activity and duration of the cramp were quantified. The discovery cohort involved three separate randomised sessions where intervals between stimulation was 60, 90, and 120 s respectively. In each session, four randomised electrical stimulation protocols were completed. Stimulation current was fixed at 10, 20, and 30% higher than m-wave stimulation current (protocols 1-3 respectively), or randomised within 4 Hz steps (protocol 4) to minimise any order effect. MAIN RESULTS: We were able to immediately replicate tolerable muscle cramp at least twice. Discovery cohort demonstrated (i) incremental changes in stimulation frequency (protocols 1-3 vs. protocol 4, i.e. order effect), and (ii) changes in stimulation current with differing protocols did not significantly alter the prevailing muscle cramp characteristics, and (iii) defining the muscle cramp characteristics elicits good-to-excellent inter-observer reliability. The validation cohort's test-retest reliability and the minimum detectable change were improved for all muscle cramp characteristics when immediately replicated more than twice at the lowest stimulation frequency. SIGNIFICANCE: This study provides evidence for a reliable method for inducing repeatable muscle cramps in abductor hallucis.

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.

The pharmacokinetics of meropenem and piperacillin-tazobactam during sustained low efficiency haemodiafiltration (SLED-HDF).

OBJECTIVE: We analysed the pharmacokinetics of meropenem and piperacillin-tazobactam in patients undergoing a standardised session of sustained low efficiency haemodiafiltration (SLED-HDF) to inform the dosing of these drugs in an acute setting. PARTICIPANTS: Six stable patients with end-stage kidney disease. METHODS: An open-label pilot pharmacokinetic study of meropenem and piperacillin-tazobactam. SLED-HDF was undertaken for 4 h. Plasma drug concentrations were measured pre- and post-filter and in the effluent at multiple time points. The pharmacokinetic data was analysed using non-compartmental methods. The fraction of time that individual plasma concentration profiles were predicted to remain above the MIC break-points for commonly isolated gram-negative pathogens during a prolonged SLED-HDF session was assessed using two targets; fT > MIC (fraction of time above the MIC) and the more aggressive fT > 4 × MIC (fraction of time above 4 × MIC). RESULTS: Meropenem total and SLED-HDF clearance ranged from 141 to 180 mL/min and 126-205 mL/min, respectively. Piperacillin total and SLED-HDF clearance values ranged from 131 to 252 mL/min and 135-162 mL/min, respectively. Our results suggest that prolonged SLED-HDF (12 h) will only maintain a sufficient meropenem and piperacillin-tazobactam plasma concentration to achieve a target of fT > MIC for gram-negative pathogens (MIC 2 mg/L-meropenem, 8 mg/L-piperacillin-tazobactam) for less than 40% of the time. Plasma concentrations would be inadequate to achieve the more aggressive target of 100 % fT > 4xMIC target recommended for critically unwell patients. CONCLUSIONS: The pharmacokinetic data obtained from this pilot study demonstrate significant quantities of meropenem and piperacillin are removed during a SLED-HDF session. This may lead to subtherapeutic concentrations of piperacillin and meropenem over the duration of HDF session. TRIAL REGISTRATION: Australasian Clinical Trials Registry Network (ACTRN12616000078459).

Recruitment and participant baseline characteristics in the dialysis outcomes in those aged 65 years or older study.

BACKGROUND: Despite an increasing number of older people commencing dialysis the impact of dialysis on their quality of life and survival, remains unclear. The Dialysis Outcomes in those aged over 65 years or older study is an accelerated prospective cohort longitudinal design study, designed to obtain sufficient health related quality of life data, linked to clinical data, to inform clinicians' and patients' decision-making with respect to end stage kidney disease (ESKD), outcomes, and options for management in New Zealand (NZ). METHODS: The study has an accelerated prospective cohort longitudinal design, comprised of cross-sectional and longitudinal components. We report the baseline data on the 225 participants enrolled in the study. Dialysis duration was grouped in tertiles from less than one year (incident patients), 1-3 years and greater than 3 years. Health related quality of life data was obtained from self-reported questionnaires including KDQoL-36, EQ-5D-3 L, FACIT, WHODAS II, and the Personal Well-being Score. RESULTS: The median age of the cohort was 71 years and two thirds were male. Three quarters of the participants were on dialysis at the baseline, with 42% of those on home dialysis (haemodialysis or peritoneal dialysis). Maori and Pacific people were over represented (20% Maori and 24% Pacific) in the sample, when compared to the general NZ population of the same age group (where 5% are Maori and 2% are Pacific). At baseline, there were no differences observed in sociodemographic, quality of life or health characteristics between the dialysis groups either by modality or duration of dialysis. CONCLUSIONS: We report the baseline characteristics of participants enrolled prospectively into a longitudinal cohort observational study examining health related quality of life factors with clinical characteristics on dialysis outcomes in a group of New Zealanders aged 65 years or older who are either on dialysis or have been educated about dialysis (BMC Nephrol 14:175, 2013). Subsequent publications are planned, analysing the prospective longitudinal data to identify key factors that determine both outcome and quality of life for individuals of this age group. TRIAL REGISTRATION: ACTRN12611000024943 .

Prevalence and risk factors for chronic kidney disease in primary health care in the southern region of New Zealand.

AIM: While the prevalence of end stage kidney disease in New Zealand (NZ) is well defined, the prevalence of chronic kidney disease (CKD) in NZ is unknown. To estimate the prevalence of and risk factors for CKD in the southern region of New Zealand. METHODS: A retrospective electronic health record cohort study using data from the Southern Primary Care register covering 94% of the population. Patients, 20 years or older were identified and linked to laboratory results for serum creatinine and urinary albumin excretion. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2 (G3-5) or the presence of albuminuria of greater than 3 mg/mmol (A2-3). Diabetes was identified from a national virtual diabetes database. From this, we estimated the prevalence of CKD by age, gender, ethnicity, deprivation and the presence of diabetes mellitus. RESULTS: Of a total adult population of 211 980, 159 799 had a serum creatinine checked and 27 905 had an estimate of albuminuria. The estimated prevalence of CKD was 11.8%. 6.3% of total population had CKD stage G3a, 2.4% G3b, 0.8% G4, 0.2% G5, 1.8% A2 albuminuria and 0.3% A3 albuminuria. Increasing age, female sex, ethnic group, social deprivation and diabetes mellitus were associated with an increased risk of CKD. 11 351 patients had a diagnosis of diabetes mellitus and were almost universally tested (99.3%) for CKD. The presence of albuminuria was strongly correlated with ethnic group, male sex and living in a deprived area. The retrospective electronic health record study with associated selection and testing bias are potential limitations of the present study. CONCLUSION: Chronic kidney disease prevalence in this region appears to be similar to other reported populations. The majority of those at risk for CKD were tested for reduced eGFR. The presence of albuminuria, an integral component of CKD diagnostic criteria, was under utilized in the non-diabetic population.

Medication Exposure and Health Outcomes in Older Patients with End-Stage Kidney Disease: A Prospective Study Undertaken in New Zealand.

BACKGROUND: The impact of multiple medication exposure on health outcomes among older patients with end-stage kidney disease (ESKD) is unknown. OBJECTIVE: The objective of this study was to identify the impact of medicine exposure on hospitalisation rates and mortality in a prospective longitudinal observational study of older dialysis patients. METHODS: Patient demographics, medication use, hospitalisation, mortality and co-morbidity data were collected through the prospective longitudinal cohort study DOS65 + (Dialysis Outcomes in those aged ≥ 65 years Study) (n = 225). Medication exposure was measured by the total number of individual medications and the number of predetermined 'medication groups'. Associations between medications prescribed at recruitment and health outcomes as measured by hospitalisation and mortality were assessed by univariate and multivariable regression analyses. RESULTS: Older ESKD patients were exposed to a median of ten (0-20) medications and eight (0-15) medication groups. Multivariate analyses estimate each additional medication increased mortality risk by 8% (relative risk [RR] = 1.08; 95% confidence interval [CI] 1.07-1.09); each medication group increased mortality risk by 11% (RR = 1.11; 95% CI 1.09-1.12). Similar trends were observed for hospitalisation. Certain medication groups were associated with reduced hospitalisation rates, namely angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (RR = 0.62; 95% CI 0.53-0.72) and dihydropyridines (RR = 0.64; 95% CI 0.54-0.76). Warfarin, gastric acid suppressants, diuretics and ß-blockers were associated with increased hospitalisation rates. Warfarin was associated with an increased mortality rate (RR = 1.40; 95% CI 1.19-1.65). CONCLUSIONS: Multiple medication exposure was prevalent in this older ESKD population, and was associated with an increased risk of mortality and hospitalisation. While this study is not able to determine the cause of these relationships, review of medication use is warranted in this population. TRIAL REGISTRATION: ACTRN12611000024943.

Endovascular Renal Denervation in End-Stage Kidney Disease Patients: Cardiovascular Protection-A Proof-of-Concept Study.

INTRODUCTION: Sympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic overactivity and blood pressure in resistant hypertension. We investigated the effect of RDN on sympathetic neural activation and left ventricular mass in patients with ESKD. METHODS: Nine ESKD (6 hemodialysis and 3 peritoneal dialysis) patients with dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a nondialysis day; at baseline, 1, 3, and 12 months post-RDN. RESULTS: At baseline sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in 8 of the 9 patients. At 12 months post-RDN, blind analysis revealed that MSNAfrequency (-12.2 bursts/min1, 95% CI [-13.6, -10.7]) and LV mass (-27 g/m2, 95% CI [-47, -8]) were reduced. Mean ambulatory BP (systolic: -24 mm Hg, 95% CI [-42, -5] and diastolic: -13 mm Hg, 95% CI [-22, -4]) was also reduced at 12 months. Office BP was reduced as early as 1 month (systolic: -25 mm Hg, 95% CI [-45, -5] and diastolic: -13 mm Hg, 95% CI [-24, -1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12 months. DISCUSSION: Catheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD.

Predictors of Health Deterioration Among Older Adults After 12 Months of Dialysis Therapy: A Longitudinal Cohort Study From New Zealand.

BACKGROUND: Involving patients in dialysis decision making is crucial, yet little is known about patient-reported experiences and patient-reported outcomes of dialysis. STUDY DESIGN: A prospective longitudinal cohort study of older patients receiving long-term dialysis. Predictors of worse health status were assessed using modified Poisson regression analysis. SETTING & PARTICIPANTS: 150 New Zealanders 65 years or older with end-stage kidney disease dialyzing at 1 of 3 nephrology centers. PREDICTORS: Patient-reported social and health characteristics based on the 36-Item Short Form Health Survey, EQ-5D, and Kidney Symptom Score questionnaires and clinical information from health records. OUTCOMES: Health status after 12 months of follow-up. RESULTS: 35% of study participants had reported worse health or had died at 12 months. Baseline variables independently associated with reduced risk for worse health status were Pacific ethnicity (relative risk [RR], 0.63; 95% CI, 0.53-0.72), greater bother on the Kidney Symptom Score (RR, 0.78; 95% CI, 0.62-0.97), and dialyzing at home with either home hemodialysis (RR, 0.55; 95% CI, 0.36-0.83) or peritoneal dialysis (RR, 0.86; 95% CI, 0.79-0.93). Baseline variables independently associated with increased risk were greater social dissatisfaction (RR, 1.66; 95% CI, 1.27-2.17), lower sense of community (RR, 1.70; 95% CI, 1.09-2.64), comorbid conditions (RR, 1.70; 95% CI, 1.09-2.64), EQ-5D anxiety/depression (RR, 1.61; 95% CI, 1.07-2.42); poor/fair overall general health (RR, 1.60; 95% CI, 1.37-1.85), and longer time on dialysis therapy (RR, 1.03; 95% CI, 1.00-1.05). LIMITATIONS: Small sample size restricted study power. CONCLUSIONS: Most older dialyzing patients studied reported same/better health 12 months later. Home-based dialysis, regardless of whether hemodialysis or peritoneal dialysis, was associated with reduced risk for worse health, and older Pacific People reported better outcomes on dialysis therapy. Social and/or clinical interventions aimed at improving social satisfaction, sense of community, and reducing anxiety/depression may favorably affect the experiences of older patients receiving long-term dialysis.

Accuracy of ethnicity data recorded in hospital-based patient clinical records and the Australia and New Zealand Dialysis and Transplant Registry.

AIM: Sustained health inequities are experienced by indigenous and minority populations. Accurate ethnicity data are fundamental to healthcare planning and provision and monitoring of health outcomes to address such inequities. This study investigated the accuracy of ethnicity data in a large clinical registry of end-stage kidney disease patients (the Australia and New Zealand Dialysis and Transplant Registry; ANZDATA) and hospital-based patient clinical records compared with self-reported ethnicity data collected in the 'Dialysis Outcomes in those aged ≥65 years' (DOS65+) study. METHODS: Self-reported ethnicity data were collected, as per national guidelines, from DOS65+ participants and compared with ethnicity data recorded for these participants in ANZDATA and hospital-based patient clinical records. Ethnicities were first prioritised and then grouped into one of the following: European, Maori, Pacific, Asian and Other. Cohen's Kappa statistics were calculated to determine overall non-random agreement. Concordances for ethnic group categories were calculated. RESULTS: There was high concordance between self-reported ethnicity and ethnicity recorded in both the ANZDATA (κ=0.95) and hospital-based patient clinical records (κ=0.93). Concordances for ethnic group categories between datasets ranged from 86% to 100%. CONCLUSION: Our findings show a high level of agreement for ethnicity recorded for end-stage kidney disease patients between the three datasets, suggesting robust data to support health planning and research. Despite this, alignment of ethnicity data collection methods, as per national guidelines, should occur for all databases used for research and clinical practice in New Zealand.

To dialyse or delay: a qualitative study of older New Zealanders' perceptions and experiences of decision-making, with stage 5 chronic kidney disease.

BACKGROUND: Issues related to renal replacement therapy in elderly people with end stage kidney disease (ESKD) are complex. There is inadequate empirical data related to: decision-making by older populations, treatment experiences, implications of dialysis treatment and treatment modality on quality of life, and how these link to expectations of ageing. STUDY POPULATION: Participants for this study were selected from a larger quantitative study of dialysis and predialysis patients aged 65 years or older recruited from three nephrology services across New Zealand. All participants had reached chronic kidney disease (CKD) stage 5 and had undergone dialysis education but had not started dialysis or recently started dialysis within the past 6 months. METHODOLOGY: Serial qualitative interviews were undertaken to explore the decision-making processes and subsequent treatment experiences of patients with ESKD.Analytical approach: A framework method guided the iterative process of analysis. Decision-making codes were generated within NVivo software and then compared with the body of the interviews. RESULTS: Interviews were undertaken with 17 participants. We observed that decision-making was often a fluid process, rather than occurring at a single point in time, and was heavily influenced by perceptions of oneself as becoming old, social circumstances, life events and health status. LIMITATIONS: This study focuses on participants' experiences of decision-making about treatment and does not include perspectives of their nephrologists or other members of the nephrology team. CONCLUSIONS: Older patients often delay dialysis as an act of self-efficacy. They often do not commit to a dialysis decision following predialysis education. Delaying decision-making and initiating dialysis were common. This was not seen by participants as a final decision about therapy. Predialysis care and education should be different for older patients, who will delay decision-making until the time of facing obvious uraemic symptoms, threatening blood tests or paternalistic guidance from their nephrologist. TRIAL REGISTRATION NUMBER: Australasian Clinical Trials Registry ACTRN 12611000024943; results.

A Population Pharmacokinetic Model for 51Cr EDTA to Estimate Renal Function.

BACKGROUND AND OBJECTIVES: 51Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw 51Cr EDTA measurements over-simplifies the disposition of 51Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for 51Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. PATIENTS AND METHODS: Data from 40 individuals who received ~7.4 MBq of 51Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24 h after the dose. A population analysis was conducted using NONMEM® version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). RESULTS: A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24 h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5 mL/min/1.73 m2 [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73 m2, respectively). CONCLUSIONS: The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). STUDY REGISTRATION: The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.