TY - JOUR AU - Hawley C. AU - Pascoe E. AU - Palmer S. AU - Strippoli G. AU - Roberts M. AU - Johnson D. AU - Cass A. AU - Craig J. AU - Hiremath S. AU - Boudville N. AU - Badve S. AU - Whalley G. AU - Teixeira-Pinto A. AU - Perkovic Vlado AB -

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. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Participants with any stages of CKD. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials with 3 or more months' follow-up that reported LVM data. INTERVENTION: Any pharmacologic or nonpharmacologic intervention. OUTCOMES: 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). LIMITATIONS: 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.

AD - 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.
Australasian Kidney Trials Network, Brisbane, Australia; Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
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.
Australasian Kidney Trials Network, Brisbane, Australia; Department of Renal Medicine, Eastern Health Clinical School, Monash University, Melbourne, Australia.
School of Public Health, University of Sydney, Sydney, Australia.
Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Australasian Kidney Trials Network, Brisbane, Australia; Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
Division of Nephrology, University of Ottawa, Ottawa, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine, The University of Queensland, Brisbane, Australia.
Australasian Kidney Trials Network, Brisbane, Australia; The George Institute for Global Health, University of Sydney, Sydney, Australia.
Unitec Institute of Technology, Auckland, New Zealand.
Australasian Kidney Trials Network, Brisbane, Australia; School of Public Health, University of Sydney, Sydney, Australia; Cochrane Kidney and Transplant Group, Sydney, Australia. AN - 27138469 BT - American Journal of Kidney Diseases DA - 169520011183 DP - NLM ET - 2016/05/04 LA - Eng LB - AUS
R&M
FY16 N1 - Badve, Sunil V
Palmer, Suetonia C
Strippoli, Giovanni F M
Roberts, Matthew A
Teixeira-Pinto, Armando
Boudville, Neil
Cass, Alan
Hawley, Carmel M
Hiremath, Swapnil S
Pascoe, Elaine M
Perkovic, Vlado
Whalley, Gillian A
Craig, Jonathan C
Johnson, David W
Am J Kidney Dis. 2016 Apr 30. pii: S0272-6386(16)30024-5. doi: 10.1053/j.ajkd.2016.03.418. N2 -

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. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Participants with any stages of CKD. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials with 3 or more months' follow-up that reported LVM data. INTERVENTION: Any pharmacologic or nonpharmacologic intervention. OUTCOMES: 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). LIMITATIONS: 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.

PY - 2016 SN - 1523-6838 (Electronic)
0272-6386 (Linking) T2 - American Journal of Kidney Diseases TI - 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 VL - pii: S0272-6386(16)30024-5. Y2 - FY16 ER -