麻豆传媒

A commonly measured biomarker of microvascular damage in kidney disease -- albuminuria -- was also associated with greater lung function decline and greater incident COPD (chronic obstructive pulmonary disease), researchers said.

Increased albuminuria was associated with moderate increases in development of moderate to severe COPD, COPD hospitalizations and deaths, and declines in lung function, as measured by forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) in the combined analysis of data from six National Heart, Lung, and Blood Institute (NHLBI)-funded studies.

Albuminuria (urine albumin-to-creatinine ratio) measures endothelial damage in the kidneys, and also correlates with microvascular dysfunction throughout the body, including pulmonary circulation.

The study findings add to the evidence that endothelial damage in the lungs may play an important role in the development and progression of COPD, suggesting that microvascular mechanisms may be promising targets for COPD prevention and treatment, wrote Elizabeth C. Oelsner, MD, of Columbia University College of Physicians and Surgeons in New York City, and colleagues, in the .

Cross-sectional studies suggest that albuminuria is increased in COPD patients, and that it is adversely associated with lung function, gas exchange, and hypoxia. Co-occurrence of pulmonary and renal endothelial cell injury has also been demonstrated on pathological samples in COPD patients and cigarette smoke-exposed mice, and angiopathy was correlated with albuminuria.

"We hypothesized that albuminuria might be associated with COPD risk because we have increasing evidence that the same type of microvascular disease that we see in the kidney can affect microvasculature in the lungs," Oelsner told 麻豆传媒. "This may actually be a cause of emphysema and COPD."

A total of 31,877 participants in the six studies were included in the analysis. Participants with prevalent clinical lung disease were excluded. Albuminuria was measured in spot samples. Lung function was assessed by spirometry.

Incident chronic lower respiratory disease (CLRD)-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional-hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth-year, cohort, smoking status, pack-years, renal function, hypertension, diabetes, and medications.

Among 10,961 participants included in the analysis with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV₁ decline was 31.5 mL/year.

Participants were followed for changes in lung function over a median of 6 years and for respiratory hospitalizations and mortality over a median of 15 years. The findings were as follows:

• For each standard deviation increase in ln-albuminuria, there was 2.81% greater FEV₁ decline (95% CI 0.86%-4.76%; P=0.0047); 11.02% greater FEV₁/FVC decline (95% CI 4.43%-17.62%; P=0.0011); and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI 2%-31%, P=0.0021)
• Each standard deviation ln-albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI 18%-34%, P<0.0001) among 14,213 participants followed for events
• The associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease, and asthma events were not significantly associated

Oelsner told 麻豆传媒 that the modest size of the observed associations suggest that measuring albuminuria is not likely to be a clinically useful predictor of COPD risk in healthy adults. But she said the findings could have important implications for future research into new drug therapies to treat the disease and other areas of research and patient monitoring.

The researchers concluded that while direct clinical applicability of their findings may be limited, "albuminuria is a non-invasive measure that could be considered in selection and monitoring of high-risk participants enrolled in clinical trials of COPD prevention, if not risk stratification in the general population."

"Our findings also highlight clinically important and well-established associations between COPD and well-known causes of albuminuria – chronic kidney disease and diabetes – while suggesting that these comorbidities may share underlying microvascular mechanisms."