Orthostatic hypotension is associated with incident chronic kidney disease: The Atherosclerosis Risk In Communities Study

Background— Orthostatic hypotension (OH) is associated with increased rates of cardiovascular disease and mortality, particularly among middle-aged persons. However, little is known about the association of OH with chronic kidney disease (CKD). Methods and Results— Postural changes in blood pressure (BP) were estimated using the difference between the average of multiple supine and standing BP measurements. OH was defined as a decrease in systolic BP ≥ 20 mm Hg, or a decrease in diastolic BP ≥ 10 mm Hg upon standing. Incident CKD was defined as an increase in serum creatinine ≥ 0.4 mg/dL at the 3- or 9-year follow-up visits, or a hospitalization (discharge) or death due to CKD. Urinary albumin-to-creatinine ratio (ACR, mg/g) was obtained at visit 4 and used to define albuminuria (ACR ≥ 30 mg/g). The association between OH and incident CKD and between OH and categories of albuminuria were modeled using adjusted Cox proportional hazard models and logistic regression, respectively. Among 12,593 individuals, 1,019 developed CKD (3.9 cases/1,000 person-years) over a mean of 16 years. A significantly increased risk of CKD was observed among individuals with OH compared to those without OH after adjustment (hazard ratio 1.67, 95% confidence interval, 1.36, 2.06). OH was associated with increased risk of albuminuria (OR 1.66, 95% CI 1.21, 2.29). Conclusions— These findings suggest that OH increases the risk of CKD in middle-aged persons. Multiple physiologic mechanisms are activated in response to gravitational pooling of blood, reduced venous return and reduced cardiac output. The autonomic nervous system, particularly the sympathetic nervous system, has an important role in the short-term regulation of blood pressure (BP). 1 Individuals with autonomic dysfunction are unable to regulate BP in response to postural changes. Orthostatic hypotension (OH), a manifestation of autonomic dysfunction, is associated with incident hypertension 2 , coronary heart disease 3 , stroke 4 and all-cause mortality 5 in middle-aged persons.