Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism:Pooled Analysis of Five Prospective General Population Cohorts

Bakhtawar K. Mahmoodi, MD, PhD; Ron T. Gansevoort, MD, PhD; Inger Anne Næss, MD, PhD; Pamela L. Lutsey, PhD, MPH; Sigrid K. Brækkan, PhD; Nic J.G.M. Veeger, PhD; Ellen E. Brodin, MD, PhD; Karina Meijer, MD, PhD; Yingying Sang, MSc; Kunihiro Matsushita, MD, PhD; Stein I. Hallan, MD, PhD; Jens Hammerstrøm, MD, PhD; Suzanne C. Cannegieter, MD, PhD; Brad C. Astor, PhD, MPH; Josef Coresh, MD, PhD; Aaron R. Folsom, MD, MPH; John-Bjarne Hansen, MD, PhD; Mary Cushman, MD, MSc

Circulation. 2012; 126: 1964-1971

Abstract
Background—Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted.

Methods and Results—We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m2, hazard ratios for VTE were 1.29 (95% confidence interval, 1.04–1.59) for eGFR 75, 1.31 (1.00–1.71) for eGFR 60, 1.82 (1.27–2.60) for eGFR 45, and 1.95 (1.26–3.01) for eGFR 30 mL/min per 1.73 m2. In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04–1.72) for ACR 30 mg/g, 1.60 (1.08–2.36) for ACR 300 mg/g, and 1.92 (1.19–3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m2 or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15–2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well.

Conclusions—Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges