Lung Dysfunction Associated with Degree of Renal Function Impairment in CKD Patients

The third leading cause of death in the United States is chronic lower respiratory disease. In the general population, the prevalence of restrictive lung dysfunction is 7% and the prevalence of obstructive lung dysfunction is 14%.  Although advanced chronic kidney disease (CKD) can severely affect the lungs, an increased prevalence of lung dysfunction is seen even in those with CKD stages 1 to 4. According to the National Health and Nutrition Examination Survey 2007-2012, the prevalence of restrictive lung dysfunction among patients with CKD is 10% and the prevalence of obstructive lung dysfunction in that patient population is 16%.

Due to fluid retention and metabolic, endocrine, and cardiovascular changes, as glomerular filtration rate (GFR) declines, pulmonary edema and respiratory muscle dysfunction become more common. Urinary protein excretion may also be linked to worsening lung function. However, according to Abdul Rashid Qureshi, MD, PhD, and colleagues, lung assessment is not part of routine clinical practice in the management of patients with CKD, and there are few data available on the prevalence, characteristics, and clinical implications of restrictive and obstructive lung dysfunction in patients with varying degrees of renal impairment.

The researchers recently conducted a study designed to examine lung function in relation to specified GFR categories in individuals with normal to reduced renal function. The study sought to identify associations of lung dysfunction with all-cause and cardiovascular disease-related mortality. Results of the study were reported online in Kidney & Blood Pressure Research [doi:10.1159/000488699].

Patients (n=404) were divided into five GFR categories according to the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines: G1 (n=31; GFR >90 mL/min/1.73 m²); G2 (n=46); G3 (n=33), G4 (n=49), and G5 (n=245; GFR <15 mL/min/1.73 m²). Participants underwent spirometry yielding lung function indices forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and peak expiratory flow (PEF).

Among the 404 participants, 63% (n=252) had normal lung function; 10% (n=42) had obstructive lung function; and 27% (n=110) had restrictive lung function at baseline. The three groups were similar in age and sex. Patients with restrictive lung function had more comorbidities (diabetes mellitus, cardiovascular disease, and protein-energy wasting [PEW]), higher levels of inflammation biomarkers (high-sensitivity C-reactive protein [hsCRP] and interleukin-6), lower physical activity, lower hand-grip strength, and more frequent use of beta blockers and statins.

The patients with restrictive lung function had low %FVC (median, 69%) and %FEV₁ (median, 73%); the decline in %FVC was more pronounced than that of %FEV₁, resulting in a high ratio of FEV₁/FVC (median, 88%).  In patients with obstructive lung function, the %FEV₁ was median 63%, with less change in %FVC (median, 82%), resulting in a markedly reduced FEV₁/FVC ratio to median 65%.

The patients with more advanced categories of GFR were more likely to have more comorbidities (diabetes mellitus, cardiovascular disease, and PEW), lower hand-grip strength, and more inflammatory biomarkers compared with patients in other GFR categories. They also had lower %FEV₁, %FVC, and %PEF; FEV₁/FVC was similar across GFR categories. Lung dysfunction, obstructive and, especially restrictive, was more common in patients with advanced GFR (categories 4 and 5).

Compared with other tertiles, there was an association between the highest tertiles of %Fev1 and %FVC and lower all-cause mortality after adjusting for tertiles of Framingham cardiovascular disease score (representing age, sex, diabetes mellitus, systolic blood pressure, use of anti-hypertensive medication, total cholesterol, high-density lipoprotein cholesterol, and smoking); presence of cardiovascular disease, PEW, and albumin; and levels of body mass index (BMI), hsCRP, and albuminuria (sub-hazard ratio [sHR], 0.49; 95% confidence interval [CI], 0.27-0.88; P=.001 and 0.56; 95% CI, 0.32-0.98; P=.04, respectively).

Following the same adjustments, compared with other tertiles, the highest tertiles of %FEV₁ was associated with lower cardiovascular disease mortality (sHR, 0.16; 95%CI, 0.04-0.69; P=.01). There was no statistical significance with the association of the highest tertile of %FVC and cardiovascular disease mortality.

After adjusting for Framingham cardiovascular risk score, presence of cardiovascular disease, PEW, and albuminuria; and levels of BMI, plasma albumin, and hsCRP, and % hand grip strength, there was an association between restrictive lung dysfunction and increased risk of mortality (sHR, 1.80; 95% CI, 1.04-3.13; P=.03). The association between obstructive lung dysfunction impairment and increased risk of mortality was not significant.

The observational design of the study was cited by the authors as a limitation to the findings, limiting the ability to draw conclusions about causality, and including only clinically stable patients of whom only a few had pre-existing lung disease, limiting the generalizability of the findings to the CKD population as a whole.

In conclusion, the authors said, “Impaired lung function, especially restrictive lung dysfunction, is a common feature of advanced CKD that associates with severity of renal failure, presence of PEW, inflammation and cardiovascular disease, and with 5-year all-cause and cardiovascular disease-related mortality. The prevalence of restrictive lung function increased in proportion to the number of comorbid conditions, PEW, inflammation, and cardiovascular disease, being present concomitantly, from 13% in patients with none of these conditions to 64% when three of them were present. Further studies in larger cohorts of CKD patients on causes and consequences of lung dysfunction, especially restrictive lung function, are warranted to confirm these findings.”

Takeaway Points

1. Researchers conducted a study to examine the association of lung function with mortality in individuals with normal to severely reduced glomerular filtration rate (GFR).
2. With decreasing GFR and higher burden of comorbidity, the prevalence of both obstructive and restrictive lung dysfunction increased; the increase was greater with restrictive lung dysfunction.
3. Both obstructive and restrictive lung dysfunction were independent predictors of increased morality risk in patients with advanced chronic kidney disease.