Connie M Rhee1, Danh V Nguyen2, Hamid Moradi3, Steven M Brunelli4, Ramanath Dukkipati5, Jennie Jing3, Tracy Nakata3, Csaba P Kovesdy6, Gregory A Brent7, Kamyar Kalantar-Zadeh3. 1. Harold Simmons Center of Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA. Electronic address: crhee1@uci.edu. 2. Division of General Internal Medicine, University of California Irvine, Orange, CA. 3. Harold Simmons Center of Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA. 4. DaVita Healthcare Partners Inc, Minneapolis, MN. 5. Division of Nephrology, Harbor-UCLA Medical Center, Torrance, CA. 6. University of Tennessee Health Science Center, Memphis, TN; Division of Nephrology, Memphis VA Medical Center, Memphis, TN. 7. Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Abstract
BACKGROUND: In the general population, circulating adiponectin is associated with a favorable cardiovascular risk profile (eg, lower triglycerides and body fat) and decreased mortality. Hemodialysis (HD) patients have comparatively higher adiponectin concentrations, but prior studies examining the adiponectin-mortality association in this population have not accounted for body composition or shown a consistent relationship. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: We examined baseline serum adiponectin concentrations in 501 HD patients across 13 dialysis centers from the prospective MADRAD (Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease) cohort (entry period, October 2011 to February 2013; follow-up through August 2013). PREDICTOR: Serum adiponectin concentration in tertiles (tertiles 1, 2, and 3 defined as ≤16.1, >16.1-<30.1, and ≥30.1-100.0 μg/mL, respectively). Adjustment variables included case-mix and laboratory test results (age, sex, race, ethnicity, vintage, diabetes, serum albumin, total iron-binding capacity, serum creatinine, white blood cell count, phosphate, hemoglobin, and normalized protein catabolic rate), body composition surrogates (subcutaneous, visceral, and total-body fat and lean body mass), and serum lipid levels (cholesterol, high-density lipoprotein cholesterol, and triglycerides). OUTCOMES: All-cause mortality using survival (Cox) models incrementally adjusted for case-mix and laboratory test results. RESULTS: Among 501 HD patients, 50 deaths were observed during 631.1 person-years of follow-up. In case-mix- and laboratory-adjusted Cox analyses, the highest adiponectin tertile was associated with increased mortality versus the lowest tertile (HR, 3.35; 95% CI, 1.50-7.47). These associations were robust in analyses that additionally accounted for body composition (HR, 3.18; 95% CI, 1.61-8.24) and lipid levels (HR, 3.64; 95% CI, 1.34-7.58). LIMITATIONS: Residual confounding cannot be excluded. CONCLUSIONS: Higher adiponectin level is associated with a 3-fold higher death risk in HD patients independent of body composition and lipid levels. Future studies are needed to elucidate underlying mechanisms and determine therapeutic targets associated with improved outcomes in HD patients.
BACKGROUND: In the general population, circulating adiponectin is associated with a favorable cardiovascular risk profile (eg, lower triglycerides and body fat) and decreased mortality. Hemodialysis (HD) patients have comparatively higher adiponectin concentrations, but prior studies examining the adiponectin-mortality association in this population have not accounted for body composition or shown a consistent relationship. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: We examined baseline serum adiponectin concentrations in 501 HDpatients across 13 dialysis centers from the prospective MADRAD (Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease) cohort (entry period, October 2011 to February 2013; follow-up through August 2013). PREDICTOR: Serum adiponectin concentration in tertiles (tertiles 1, 2, and 3 defined as ≤16.1, >16.1-<30.1, and ≥30.1-100.0 μg/mL, respectively). Adjustment variables included case-mix and laboratory test results (age, sex, race, ethnicity, vintage, diabetes, serum albumin, total iron-binding capacity, serum creatinine, white blood cell count, phosphate, hemoglobin, and normalized protein catabolic rate), body composition surrogates (subcutaneous, visceral, and total-body fat and lean body mass), and serum lipid levels (cholesterol, high-density lipoprotein cholesterol, and triglycerides). OUTCOMES: All-cause mortality using survival (Cox) models incrementally adjusted for case-mix and laboratory test results. RESULTS: Among 501 HDpatients, 50 deaths were observed during 631.1 person-years of follow-up. In case-mix- and laboratory-adjusted Cox analyses, the highest adiponectin tertile was associated with increased mortality versus the lowest tertile (HR, 3.35; 95% CI, 1.50-7.47). These associations were robust in analyses that additionally accounted for body composition (HR, 3.18; 95% CI, 1.61-8.24) and lipid levels (HR, 3.64; 95% CI, 1.34-7.58). LIMITATIONS: Residual confounding cannot be excluded. CONCLUSIONS: Higher adiponectin level is associated with a 3-fold higher death risk in HDpatients independent of body composition and lipid levels. Future studies are needed to elucidate underlying mechanisms and determine therapeutic targets associated with improved outcomes in HDpatients.
Keywords:
Adiponectin; MADRAD (Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease) study; anthropometry; body composition; body fat; body mass index (BMI); cardiovascular disease (CVD); end-stage renal disease; hemodialysis; lipids; mortality; renal replacement therapy (RRT)
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