Acute kidney injury in hospitalized patients with nonexacerbated chronic obstructive pulmonary disease

The current study retrospectively analyzed the clinical data of adult COPD patients (≥18 years) who received treatment at Sichuan Provincial People’s Hospital between January 2011 and September 2016. All the patients with COPD discharge diagnoses were selected. The patients with a diagnosis of AECOPD or any comorbid respiratory infection were considered to have AECOPD, while the others were considered to have NECOPD. The exclusion criteria were as follows: 1) the patient’s baseline serum creatinine levels were unavailable; 2) the patient had advanced chronic kidney disease (CKD), i.e., an estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m²; a minimum SCr level > 353.6 μmol/L (4 mg/dL) during the hospital stay; a clinical diagnosis of stage 5 CKD; or the receipt of a replacement kidney before the onset of AKI; 3) the patient had a maximum SCr level < 53 μmol/L during the hospital stay (to avoid an AKI diagnosis due to a very slight SCr increase and potential malnutrition); 4) the patient previously underwent kidney transplantation or amputation; and 5) the patient had incomplete clinical records that were unable to supply the data for the current research.

Based on the clinical records, medical costs, lengths of hospital stay and in-hospital mortality rates associated with AKI were analyzed as medical burdens; the main outcome was in-hospital mortality.

AKI was diagnosed according to the criteria provided by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines; AKI was confirmed if the SCr value increased by more than 50% compared to the baseline value within 7 days [10]. Considering that the SCr tests before admission are frequently not available, the lowest creatinine level from 1 month before admission to the time of discharge was regarded as the baseline for community-acquired (CA-) AKI. Patients admitted to the hospital with AKI based on a creatinine measurement within 48 h of hospital admission were considered to have CA-AKI [11]; the other patients were considered to have hospital-acquired (HA-) AKI [10]. CKD was classified based on the eGFR, which was calculated by the minimal SCr value within 1 year, according to the EPI equation of the Chronic Kidney Disease Epidemiology Collaboration [12].

Complications were adjusted for based on discharge diagnoses, and the Charlson comorbidity index (CCI) score was evaluated (the CCI is a scoring system that assigns weights to mortality-related comorbid conditions, and it involves 19 comorbidities, namely, myocardial infarction, congestive heart failure, peripheral disease, cerebrovascular disease, chronic pulmonary disease, dementia, connective tissue disease, peptic ulcer disease, mild liver disease, diabetes without end-organ damage, hemiplegia, mild to moderate renal disease, diabetes with end-organ damage, tumor without metastasis, leukemia, lymphoma, moderate or severe liver disease and metastatic solid tumor) [13]. The total CCI score was used as the primary index for predicting in-hospital mortality [14]. The renal disease item in the CCI was assessed based on either a corresponding diagnosis of moderate to severe renal disease or an eGFR < 45 ml/min/1.73m². We also calculated the CCI score after removing renal disease to avoid potential collinearity between CKD and CCI when they were both included as variables in one multivariable analysis. Anemia was defined as a minimum hemoglobin (Hb) concentration < 120 g/L during hospitalization, regardless of sex, according to the World Health Organization standard, because amenorrhea data was unavailable in the female subjects. The Hb level was stratified as < 6 g/dL, 6–8.9 g/dL, 9–11.9 g/dL and ≥ 12 g/dL.

Measurement data are presented as the median [25th quartile (Q25)-75th quartile Q75)], and independent Mann-Whitney-U tests were performed for group comparisons. Enumeration data are presented as case numbers, and χ² tests were used for the comparisons. Multiple comparisons were corrected using the Bonferroni method. Univariate logistic regression was performed, and the variables with a statistically significant difference were included in the multivariate logistic regression analysis by a stepwise forward conditional model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All statistical analyses were performed with SPSS 24.0, and a bilateral P value < 0.05 was considered statistically significant.

A total of 11,199 patients hospitalized for COPD were investigated during this study, 4898 patients were nonacute. After applying the exclusion criteria, this study enrolled 2897 NECOPD patients. Compared with the excluded patients, those enrolled were 1 year older (75 vs 74, P = 0.003), more often male (77.9% vs 67.2%, P < 0.001), less often had cor pulmonale (22.8% vs 55.9%, P < 0.001), and had an eGFR that was 4.7 ml/min/1.73m² lower (91.7 vs 87.0, P < 0.001). Among these patients, 205 patients (7.1%) had CA-AKI, and 349 patients (12.0%) had HA-AKI (Fig. 1). In the CA-AKI and HA-AKI groups, 62 (9.4%) and 113 (17.1%) patients, respectively, presented with cor pulmonale complications. The general data of the patients with the different types of AKI are summarized in Table 1.

Due to a lack of preadmission data for the CA-AKI group, only the associations between clinical data and the development of HA-AKI were analyzed in this study. As medication concerned sensitive data, only drugs that are commonly used for diseases of respiratory origin with potential renal toxicity were retrieved in this study. The prescription time and AKI occurrence were analyzed, and only the medicines used before AKI were further studied. These drugs included proton pump inhibitors (use prevalence, 55.0%), diuretics (including osmotic diuretics such as mannitol; use prevalence, 28.6%), rennin-angiotensin system inhibitors (use prevalence, 26.7%), nonsteroidal anti-inflammatory drugs (NSAIDs; use prevalence, 18.8%), intravenous diodone (use prevalence, 12.2%), intravenous antihemorrhagic drugs (use prevalence, 10.0%), aminoglycosides (use prevalence, 4.8%) and glycopeptides (use prevalence, 2.4%). Univariate regression showed that increased age, female gender, cor pulmonale complication, CKD and diabetes were associated with HA-AKI. Among the drugs with a use prevalence greater than 10%, diuretics and intravenous diodones used before AKI were associated with HA-AKI. Despite a low use prevalence, glycopeptides were associated with the development of HA-AKI (Table 2). The variables with P values < 0.10, i.e., age > 65 years, female gender, diabetes complication, cor pulmonale complication, CKD stage, and pre-AKI diuretic, diodone and glycopeptide use, were included in the multivariate model, according to the univariate regression analyses (Table 2).

A total of 164 patients (5.7%) died during hospitalization. Compared with the surviving patients, the nonsurviving patients were older, more likely be female and had higher comorbidity burdens (Table 3). The relation between AKI and in-hospital mortality was further analyzed. According to the univariate regression analysis, age > 65 years, female gender, cor pulmonale complication, CKD stage, CCI score without renal disease, Hb level (according to the minimum values during hospital stay, < 6 g/dL, 6–8.9 g/dL, 9–11.9 g/dL and ≥ 12 g/dL) and AKI type were associated with in-hospital mortality (Table 4). A multivariate logistic regression model was then constructed for further analysis. Because the CCI already considers CKD, the CCI score without renal disease but not the CCI score with renal disease was included in the model. In addition, due to the interaction between AKI and cor pulmonale according to the preliminary analysis, the cor pulmonale variable was excluded from the multivariate model. The results showed an independent association of in-hospital mortality with increased age [OR 2.051 (95% CI 1.305–3.591)], decreased Hb [OR 1.140 (95% CI 0.727–1.786) for 9–11.9 g/dL; OR 2.165 (95% CI 1.305–3.591) for 6–8.9 g/dL; OR 6.403 (95% CI 2.986–13.730) for < 6 g/dL] and AKI [OR 2.186 (95% CI 1.072–4.455) for CA-AKI; OR 16.949 (95% CI 11.483–25.016) for HA-AKI] (Fig. 2a). Then, we analyzed the independent relation between AKI and in-hospital mortality stratified by cor pulmonale. In both of the subgroups (with or without cor pulmonale), only HA-AKI was an independent risk factor for in-hospital mortality [OR 13.909 (95% CI 8.699–22.238) in the non-cor pulmonale subgroup; OR 26.604 (95% CI 12.166–58.176) in the cor pulmonale subgroup]; however, CA-AKI was not [OR 2.070 (95% CI 0.888–4.828) in the non-cor pulmonale subgroup; OR 2.532 (95% CI 0.647–9.910) in the cor pulmonale subgroup] (Fig. 2b and c).