title: Rationale and design of the Myocardial Microinjury and Cardiac Remodeling Extension Study in the Sodium Lowering in Dialysate trial (Mac-SoLID study).
abstract: 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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.
authors.forename: Joanna Leigh
authors.initials: JL
authors.lastname: Dunlop
authors.forename: Alain Charles
authors.initials: AC
authors.lastname: Vandal
authors.forename: Janak Rashme
authors.initials: JR
authors.lastname: de Zoysa
authors.forename: Ruvin Sampath
authors.initials: RS
authors.lastname: Gabriel
authors.forename: Lukas Mathias
authors.initials: LM
authors.lastname: Gerber
authors.forename: Imad Adbi
authors.initials: IA
authors.lastname: Haloob
authors.forename: Christopher John
authors.initials: CJ
authors.lastname: Hood
authors.forename: John Hamilton
authors.initials: JH
authors.lastname: Irvine
authors.forename: Philip James
authors.initials: PJ
authors.lastname: Matheson
authors.forename: David Owen Ross
authors.initials: DO
authors.lastname: McGregor
authors.forename: Kannaiyan Samuel
authors.initials: KS
authors.lastname: Rabindranath
authors.forename: John Benedict William
authors.initials: JB
authors.lastname: Schollum
authors.forename: David John
authors.initials: DJ
authors.lastname: Semple
authors.affiliation: Faculty of Medical and Health Sciences, University of Auckland, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand. mrmarsh@woosh.co.nz.
authors.forename: Mark Roger
authors.initials: MR
authors.lastname: Marshall
mesh_terms: D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D015314:Dialysis Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D009520:New Zealand / Q000453:epidemiology; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D012648:Self Care / Q000379:methods; D016037:Single-Blind Method; D012964:Sodium / Q000008:administration & dosage* / Q000009:adverse effects; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D015314:Dialysis Solutions; D012964:Sodium