Kelly J Hunt1, Alicia J Jenkins2, Dongxu Fu3, Danielle Stevens4, Jian-Xing Ma5, Richard L Klein6, Madona Azar3, Sarah X Zhang7, Maria F Lopes-Virella6, Timothy J Lyons2. 1. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States of America; Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America. Electronic address: huntke@musc.edu. 2. Division of Endocrinology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States of America. 3. Section of Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America. 4. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States of America. 5. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America. 6. Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC, United States of America; Division of Endocrinology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States of America. 7. Department of Ophthalmology and Ross Eye Institute, University at Buffalo & SUNY Eye Institute, State University of New York, Buffalo, NY, United States of America.
Abstract
BACKGROUND: To determine if serum pigment epithelium-derived factor (PEDF) levels predict cardiovascular events, renal dysfunction and mortality in the Veterans Affairs Diabetes Study (VADT). METHODS: PEDF was evaluated in relation to subsequent cardiovascular outcomes, mortality, and renal dysfunction (defined as urinary albumin creatinine ratio (ACR) ≥300 mg/g), or chronic kidney disease (CKD) stages 3 (eGFR<60 ml/min) or 4 (eGFR<60 and <30 ml/min respectively). PEDF was measured by ELISA on sera from 881 participants collected a median (range) of 1.7 (0-5.0) years post-baseline, and later, from 832 participants 4.0 (1.5-6.9) years post-baseline. RESULTS: In 743 participants, PEDF was measured at both time-points. PEDF increased over time from (mean ± SD) 10.5 ± 4.03 to 11.0 ± 4.86 ng/ml (paired t-test p = 0.0092). Lower eGFR (p < 0.01), higher serum creatinine (p < 0.01) and urinary ACR (p < 0.01) were associated with increasing PEDF. Multivariate event time models included either one or two follow-up windows (i.e., between first and second PEDF measures; and, when available, from second PEDF measure until study-end). PEDF tertiles were not associated with cardiovascular events, but were significantly associated with all-cause mortality [HR = 2.00 (1.03, 3.89) comparing first to third tertile] in models adjusted for age, minority status, VADT treatment arm and prior cardiovascular event status. Higher PEDF levels also associated with development of kidney dysfunction with adjusted HRs (95% CI comparing third to first PEDF tertiles: 2.74 (1.71, 4.39) for stage 3 CKD; and 3.84 (95% CI: 1.17, 12.5) for stage 4 CKD. CONCLUSIONS: Over 2-years, higher serum PEDF levels predicted advanced nephropathy in patients with type 2 diabetes. Published by Elsevier Inc.
BACKGROUND: To determine if serum pigment epithelium-derived factor (PEDF) levels predict cardiovascular events, renal dysfunction and mortality in the Veterans Affairs Diabetes Study (VADT). METHODS:PEDF was evaluated in relation to subsequent cardiovascular outcomes, mortality, and renal dysfunction (defined as urinary albumin creatinine ratio (ACR) ≥300 mg/g), or chronic kidney disease (CKD) stages 3 (eGFR<60 ml/min) or 4 (eGFR<60 and <30 ml/min respectively). PEDF was measured by ELISA on sera from 881 participants collected a median (range) of 1.7 (0-5.0) years post-baseline, and later, from 832 participants 4.0 (1.5-6.9) years post-baseline. RESULTS: In 743 participants, PEDF was measured at both time-points. PEDF increased over time from (mean ± SD) 10.5 ± 4.03 to 11.0 ± 4.86 ng/ml (paired t-test p = 0.0092). Lower eGFR (p < 0.01), higher serum creatinine (p < 0.01) and urinary ACR (p < 0.01) were associated with increasing PEDF. Multivariate event time models included either one or two follow-up windows (i.e., between first and second PEDF measures; and, when available, from second PEDF measure until study-end). PEDF tertiles were not associated with cardiovascular events, but were significantly associated with all-cause mortality [HR = 2.00 (1.03, 3.89) comparing first to third tertile] in models adjusted for age, minority status, VADT treatment arm and prior cardiovascular event status. Higher PEDF levels also associated with development of kidney dysfunction with adjusted HRs (95% CI comparing third to first PEDF tertiles: 2.74 (1.71, 4.39) for stage 3 CKD; and 3.84 (95% CI: 1.17, 12.5) for stage 4 CKD. CONCLUSIONS: Over 2-years, higher serum PEDF levels predicted advanced nephropathy in patients with type 2 diabetes. Published by Elsevier Inc.
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