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.

Figure 1. Cumulative incidence curves for incident ESRD by (A) percent-predicted FVC and (B) FEV₁/FVC

The thresholds of quartiles (%) are as follows: white men, 90.1, 98.9, and 108.0; white women, 95.1, 105.0, and 114.4; black men, 85.3, 94.9, and 103.8; and black women, 89.1, 99.5, and 110.1, for percent-predicted FVC; white men, 68.6, 74.0, and 78.2; white women, 71.5, 75.7, and 79.3; black men, 70.9, 76.5, and 80.7; and black women, 73.8, 78.5, and 82.0, for FEV₁/FVC. Abbreviations: ESRD, end-stage renal disease; FEV₁, forced expiratory volume in 1 second of expiration; FVC, forced vital capacity

Figure 1. Cumulative incidence curves for incident ESRD by (A) percent-predicted FVC and (B) FEV₁/FVC

The thresholds of quartiles (%) are as follows: white men, 90.1, 98.9, and 108.0; white women, 95.1, 105.0, and 114.4; black men, 85.3, 94.9, and 103.8; and black women, 89.1, 99.5, and 110.1, for percent-predicted FVC; white men, 68.6, 74.0, and 78.2; white women, 71.5, 75.7, and 79.3; black men, 70.9, 76.5, and 80.7; and black women, 73.8, 78.5, and 82.0, for FEV₁/FVC. Abbreviations: ESRD, end-stage renal disease; FEV₁, forced expiratory volume in 1 second of expiration; FVC, forced vital capacity

Figure 2. Adjusted cause-specific hazard ratios of ESRD associated with 10% decrease of (A) percent-predicted FVC and (B) FEV₁/FVC in predefined subgroups

Data are adjusted for age, sex, race, education levels, height, known cardiovascular and kidney risk factors (i.e., diabetes, systolic blood pressure, antihypertensive medication, history of cardiovascular disease, smoking status, cigarette-years of smoking, body mass index, eGFR, and total and HDL cholesterol), and inflammatory marker (i.e., white blood cell count). Abbreviations: DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; FEV₁, forced expiratory volume in 1 second of expiration; FVC, forced vital capacity

Figure 2. Adjusted cause-specific hazard ratios of ESRD associated with 10% decrease of (A) percent-predicted FVC and (B) FEV₁/FVC in predefined subgroups

Data are adjusted for age, sex, race, education levels, height, known cardiovascular and kidney risk factors (i.e., diabetes, systolic blood pressure, antihypertensive medication, history of cardiovascular disease, smoking status, cigarette-years of smoking, body mass index, eGFR, and total and HDL cholesterol), and inflammatory marker (i.e., white blood cell count). Abbreviations: DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; FEV₁, forced expiratory volume in 1 second of expiration; FVC, forced vital capacity

Figure 3. Cumulative incidence curves for incident ESRD by lung function patterns

Abbreviations: ESRD, end-stage renal disease