Background. Dialysate [Na ⁺ ] is often overlooked as a contributor to hypertension in patients on haemodialysis (HD). We report observational experience with a facility level decrease in dialysate [Na ⁺ ] from 141 mmol/l to 138 mmol/l, in the absence of concurrent change with respect to dietary sodium regulation. Methods. The sample comprised all patients ( n = 52) dialysing at a single HD facility over an 8-month period flanking the change in dialysate [Na ⁺ ]. Outcomes included repeated observations of blood pressure (BP), interdialytic weight gain (IDWG), pre-dialysis plasma [Na ⁺ ] and adverse events. Predictors other than dialysate [Na ⁺ ] included patient demographics, clinical characteristics and number of antihypertensive medications. The study used a longitudinal unbalanced panel design, and hierarchical linear and Poisson mixed models. Results. In multivariate analyses, the change in dialysate [Na ⁺ ] was associated with a statistically significant small to medium-sized decrease in pre- and post-dialysis systolic and diastolic BP, pre-dialysis plasma [Na ⁺ ], but not IDWG. Change was greatest in the patient tertile with the highest initial BP. There was no change in the frequency of adverse events. Modelling dialysate [Na ⁺ ] exposure as the diffusion gradient from dialysate to blood water did not improve the strength of associations. Conclusions. A facility level decrease in dialysate [Na ⁺ ] from 141 mmol/l to 138 mmol/l appears to be safe and well tolerated, and a useful means of improving BP control. The lack of change in IDWG probably reflects lack of dietary salt restriction, and but does raise the issue of volume-independent effects of sodium exposure on BP.

Introduction: Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1–3) due to ADPKD. Methods and analysis: A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m ² ) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety. Ethics and dissemination: The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD. Trial registration number: ANZCTR12614001216606.

Significance Statement: Because fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality, there is a global trend to use low-sodium dialysate in hemodialysis with the goal of reducing fluid overload. To investigate whether lower dialysate sodium during hemodialysis improves left ventricular mass, the authors conducted a randomized clinical trial of 99 adults that compared use of low-sodium dialysate (135 mM) with conventional dialysate (140 mM) for 12 months. Although participants with lower dialysate sodium showed significant improvement in fluid status, the intervention had no effect on left ventricular mass index. The intervention also increased intradialytic hypotension. Given these findings, the current trend to lower dialysate sodium should be reassessed, pending the results of large trials with hard clinical end points. 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.

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

Metformin associated lactic acidosis in Auckland City Hospital 2005 to 2009