CKD and Risk for Hospitalization With Infection: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Individuals on dialysis therapy have a high risk for infection, but risk for infection in earlier stages of chronic kidney disease has not been comprehensively described.

Study design: Observational cohort study.

Setting & participants: 9,697 participants (aged 53-75 years) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed up from 1996 to 1998 through 2011.

Predictors: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR).

Outcomes: Risk for hospitalization with infection and death during or within 30 days of hospitalization with infection.

Results: During follow-up (median, 13.6 years), there were 2,701 incident hospitalizations with infection (incidence rate, 23.6/1,000 person-years) and 523 infection-related deaths. In multivariable analysis, HRs of incident hospitalization with infection as compared to eGFRs≥90mL/min/1.73m² were 2.55 (95% CI, 1.43-4.55), 1.48 (95% CI, 1.28-1.71), and 1.07 (95% CI, 0.98-1.16) for eGFRs of 15 to 29, 30 to 59, and 60 to 89mL/min/1.73m², respectively. Corresponding HRs were 3.76 (95% CI, 1.48-9.58), 1.62 (95% CI, 1.20-2.19), and 0.99 (95% CI, 0.80-1.21) for infection-related death. Compared to ACRs<10mg/g, HRs of incident hospitalization with infection were 2.30 (95% CI, 1.81-2.91), 1.56 (95% CI, 1.36-1.78), and 1.34 (95% CI, 1.20-1.50) for ACRs≥300, 30 to 299, and 10 to 29mg/g, respectively. Corresponding HRs were 3.44 (95% CI, 2.28-5.19), 1.57 (95% CI, 1.18-2.09), and 1.39 (95% CI, 1.09-1.78) for infection-related death. Results were consistent when separately assessing risk for pneumonia, kidney and urinary tract infections, bloodstream infections, and cellulitis and when taking into account recurrent episodes of infection.

Limitations: Outcome ascertainment relied on diagnostic codes at time of discharge.

Conclusions: Increasing provider awareness of chronic kidney disease as a risk factor for infection is needed to reduce infection-related morbidity and mortality.

Keywords: Chronic kidney disease (CKD); albuminuria; bacteremia; cellulitis; chronic kidney failure; chronic renal insufficiency; glomerular filtration rate (GFR); hospitalization; infection; infectious disease; kidney function; pneumonia; proteinuria; respiratory tract infections; urinary tract infections.

Figure 1. Adjusted hazard ratio of hospitalization with infection by eGFR and ACR categories

Abbreviations: GFR, glomerular filtration rate; ACR, albumin-creatinine ratio. Green: low risk; yellow: moderately increased risk; orange: high risk; red, very high risk. For each category, hazard ratio and its 95% confidence interval were presented in the first row, and n= denotes number of events and number of individuals in the second row. The model was adjusted for age, race, sex, body mass index, smoking status, alcohol consumption, education level, use of antineoplastic agents and steroids, hypertension, diabetes, history of cancer, chronic obstructive pulmonary disease, prior heart failure, prior coronary disease, and prior stroke.

Figure 1. Adjusted hazard ratio of hospitalization with infection by eGFR and ACR categories

Abbreviations: GFR, glomerular filtration rate; ACR, albumin-creatinine ratio. Green: low risk; yellow: moderately increased risk; orange: high risk; red, very high risk. For each category, hazard ratio and its 95% confidence interval were presented in the first row, and n= denotes number of events and number of individuals in the second row. The model was adjusted for age, race, sex, body mass index, smoking status, alcohol consumption, education level, use of antineoplastic agents and steroids, hypertension, diabetes, history of cancer, chronic obstructive pulmonary disease, prior heart failure, prior coronary disease, and prior stroke.

Figure 2. Adjusted relative hazards for hospitalization with infection stratified by the types of infection

(A) eGFR; and (B) ACR. The model was adjusted for age, race, sex, body mass index, smoking status, alcohol consumption, education level, use of antineoplastic agents and steroids, history of hypertension, diabetes, cancer, chronic obstructive pulmonary disease, prior heart failure, prior coronary disease, and prior stroke, and the ACR categories for the analysis of eGFR and the eGFR categories for the analysis of ACR. The squares represent the point estimate of relative hazard, and the horizontal lines indicate corresponding 95% confidence intervals. Abbreviations: eGFR, estimated glomerular filtration rate; ACR, albumin-creatinine ratio; HR, hazard ratio; CI, confidence interval.