title: The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Left ventricular mass (LVM) is a widely used surrogate end point in randomized trials involving people with chronic kidney disease (CKD) because treatment-induced LVM reductions are assumed to lower cardiovascular risk. The aim of this study was to assess the validity of LVM as a surrogate end point for all-cause and cardiovascular mortality in CKD.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Participants with any stages of CKD.
  
  
  METHODS
  Randomized controlled trials with 3 or more months' follow-up that reported LVM data.
  
  
  METHODS
  Any pharmacologic or nonpharmacologic intervention.
  
  
  RESULTS
  The surrogate outcome of interest was LVM change from baseline to last measurement, and clinical outcomes of interest were all-cause and cardiovascular mortality. Standardized mean differences (SMDs) of LVM change and relative risk for mortality were estimated using pairwise random-effects meta-analysis. Correlations between surrogate and clinical outcomes were summarized across all interventions combined using bivariate random-effects Bayesian models, and 95% credible intervals were computed.
  
  
  RESULTS
  73 trials (6,732 participants) covering 25 intervention classes were included in the meta-analysis. Overall, risk of bias was uncertain or high. Only 3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials; SMD, -0.13; 95% CI, -0.23 to -0.03), renin-angiotensin-aldosterone system inhibitors (13 trials; SMD, -0.28; 95% CI, -0.45 to -0.12), and isosorbide mononitrate (2 trials; SMD, -0.43; 95% CI, -0.72 to -0.14). All interventions had uncertain effects on all-cause and cardiovascular mortality. There were weak and imprecise associations between the effects of interventions on LVM change and all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95% credible interval, -0.13 to 0.59) and cardiovascular mortality (13 trials; 2,327 participants; correlation coefficient, 0.30; 95% credible interval, -0.54 to 0.76).
  
  
  CONCLUSIONS
  Limited long-term data, suboptimal quality of included studies.
  
  
  CONCLUSIONS
  There was no clear and consistent association between intervention-induced LVM change and mortality. Evidence for LVM as a valid surrogate end point in CKD is currently lacking.
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia; Department of Nephrology, St. George Hospital, Sydney, Australia; The George Institute for Global Health, University of Sydney, Sydney, Australia. Electronic address: sbadve@georgeinstitute.org.au.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Badve
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.affiliation: School of Public Health, University of Sydney, Sydney, Australia; Diaverum Scientific Office and Diaverum Academy, Lund, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Italy.
authors.forename: Giovanni F M
authors.initials: GFM
authors.lastname: Strippoli
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; Department of Renal Medicine, Eastern Health Clinical School, Monash University, Melbourne, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Roberts
authors.affiliation: School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Armando
authors.initials: A
authors.lastname: Teixeira-Pinto
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Boudville
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
authors.affiliation: Division of Nephrology, University of Ottawa, Ottawa, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Swapnil S
authors.initials: SS
authors.lastname: Hiremath
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Pascoe
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Unitec Institute of Technology, Auckland, New Zealand.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Whalley
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Public Health, University of Sydney, Sydney, Australia; Cochrane Kidney and Transplant Group, Sydney, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
mesh_terms: D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D002423:Cause of Death; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D009929:Organ Size; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000401:mortality*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers
keywords: LVM regression; Left ventricular mass (LVM); cardioprotection; cardiovascular mortality; chronic kidney disease (CKD); erythropoiesis-stimulating agent (ESA); left ventricular hypertrophy; meta-analysis; nitrate; renin-angiotensin-aldosterone system (RAAS) inhibitor; surrogate endpoint; surrogate outcome