Lung Function and Incident Kidney Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD).

Study design: Prospective cohort study.

Setting & participants: 14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012.

Predictors: Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV₁/FVC) at baseline determined with spirometry.

Outcomes: Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ≥25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m², or CKD-related hospitalizations/deaths) as the secondary outcome.

Results: During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV₁/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV₁/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV₁/FVC≥70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC≥80% and FEV₁/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV₁/FVC≥70%, or percent-predicted FVC≥80% and FEV₁/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD.

Limitations: Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline.

Conclusions: Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.

Keywords: Atherosclerosis Risk in Communities (ARIC) Study; Lung function; chronic kidney disease (CKD); end-stage renal disease (ESRD); estimated glomerular filtration rate (eGFR); obstructive lung function; restrictive lung function; spirometry.