Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Arginine vasopressin promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increased water intake reduces arginine vasopressin and urine osmolality and may slow kidney cyst growth. METHODS: In this randomized controlled 3-year clinical trial, we randomly assigned adults with ADPKD who had a height-corrected total kidney volume in Mayo imaging subclass categories 1B to 1E and an estimated glomerular filtration rate of 30 ml/min/1.73 m2 or greater to (1) water intake prescribed to reduce 24-hour urine osmolality to 270 mOsmol/kg or less or (2) ad libitum water intake irrespective of 24-hour urine osmolality. The primary end point was the percentage annualized rate of change in height-corrected total kidney volume. RESULTS: A total of 184 patients participated in either the ad libitum water intake group (n=92) or the prescribed water intake group (n=92). Over 3 years, there was no difference in the annualized rate of change in height-corrected total kidney volume between the ad libitum (7.8% per year; 95% confidence interval [CI], 6.6 to 9.0) and prescribed (6.8% per year; 95% CI, 5.8 to 7.7) water intake groups (mean difference, −0.97% per year; 95% CI, −2.37 to 0.44; P=0.18). The difference in mean 24-hour urine osmolality between the ad libitum and prescribed water intake groups was −91 mOsmol/kg (95% CI, −127 to −54 mOsmol/kg), with 52.3% of patients achieving adherence to the target 24-hour urine osmolality and no reduction in serum copeptin over 3 years. The frequency of adverse events was similar between groups. CONCLUSIONS: For patients with ADPKD, prescribed water intake was not associated with excess adverse events and achieved the target 24-hour urine osmolality for half of the patients but did not reduce copeptin or slow the growth of total kidney volume over 3 years compared with ad libitum water intake. (Funded by the National Health and Medical Research Council of Australia [grant GNT1138533], Danone Research, PKD Australia, the University of Sydney, and the Westmead Medical Research Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12614001216606).

Randomised controlled trial to determine the efficacy and safety of prescribed water intake to prevent kidney failure due to autosomal dominant polycystic kidney disease (PREVENT-ADPKD).

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 m2) 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.

Effect of antimicrobial locks for tunneled hemodialysis catheters on bloodstream infection and bacterial resistance: a quality improvement report.

BACKGROUND: Catheter-restricted antimicrobial lock (AML) use reduces catheter-associated bloodstream infection (CA-BSI) in clinical trial settings, but may not be as effective in clinical settings and may increase bacterial resistance. DESIGN: Quality improvement report analyzed using a cross-sectional time series (unbalanced panel) design. SETTING & PARTICIPANTS: The study cohort comprised all prevalent adults treated with hemodialysis through a tunneled catheter for any, but not necessarily all, of the time from January 1, 2003, to June 30, 2006, in Manukau City, New Zealand (135,346 catheter-days, 404 tunneled catheters, 320 patients). QUALITY IMPROVEMENT PLAN: Catheter-restricted AMLs (heparin plus gentamicin) for all tunneled catheters from July 1, 2004. MEASURES: Repeated observations of CA-BSI, hospitalization, tunneled catheter removal, and death from CA-BSI analyzed by using generalized estimating equations with a single level of clustering for each tunneled catheter and patterns of bacterial resistance analyzed by using simple descriptive statistics. RESULTS: AML use was associated with reductions in rates of CA-BSI and hospitalization for CA-BSI by 52% and 69% for patients with tunneled catheters locked continuously with AMLs since their insertion compared with those with tunneled catheters that were not, respectively. AML exposure also was associated with a trend to increased gentamicin resistance amongst coagulase-negative staphylococci isolates, a pattern similar to that observed for BSIs in our general hemodialysis population in which tunneled catheters were not the source of BSI, but different from that in the general non-end-stage renal disease population in the region. LIMITATIONS: This is an uncontrolled observational study and cannot prove causality. The follow-up period of 18 months is longer than for other studies, but still too short to definitely answer whether AML use drives bacterial resistance. CONCLUSIONS: A change to use of AMLs may improve clinical outcomes; however, additional study of associated bacterial resistance is needed before AML use becomes standard care.