What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic Kidney Disease (n=19071). Intervention: Stage 3/4 Chronic Kidney Disease (eGFR 15-59 ml/min/1.73 m2) vs. Normal kidney function (eGFR ≥90 ml/min/1.73 m2). Primary outcome: Incident venous thromboembolism (VTE) (RR 1.71, 95% CI 1.18 to 2.49, p=0.005).

November 22, 2007

Chronic Kidney Disease Increases Risk for Venous Thromboembolism

Key Result

Stage 3/4 chronic kidney disease independently increased the risk of incident venous thromboembolism by 71% compared to normal kidney function (adjusted RR 1.71).

Study Design

Type

Cohort (n=19,071)

Multicenter

Yes

Structured PICO

Does chronic kidney disease increase the risk of incident venous thromboembolism in middle-aged and elderly adults?

Population

19,071 middle-aged and elderly adults (mean age 59 yr) from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study (combining ARIC and CHS cohorts). Key exclusions: baseline history of VTE, cancer, or taking warfarin.

Intervention

Stage 3/4 chronic kidney disease (eGFR 15 to 59 ml/min per 1.73 m2) and mildly decreased kidney function (eGFR 60 to 89 ml/min per 1.73 m2)

Comparator

Normal kidney function (eGFR >90 ml/min per 1.73 m2)

Outcome

Incident venous thromboembolism (VTE)hard clinical

Middle-aged and elderly patients with stage 3/4 chronic kidney disease have a significantly increased risk of incident venous thromboembolism compared to those with normal kidney function.

Main Result

Effect estimate: RR 1.71 (95% CI 1.18 to 2.49)

Absolute Event Rate: 4.5% vs 1.5%

p-value: p=0.005

Limitations

Renal function estimated by the MDRD formula and serum creatinine is not as accurate as direct measurement.
Estimation of renal function was based on only one measure of serum creatinine and may be subject to intraindividual variation.
Creatinine was measured on average 11.8 years before incident VTE events, and changes in kidney function during the interval could result in misclassification.
Pooled two large population-based studies, which could have differences in exposure measurement.
Lack of information on proteinuria before VTE onset.
VTE cases could have been missed if events did not occur in the hospital or were not recognized by clinicians.

Abstract

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval CI 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.

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