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. 2020 Sep;95(9):1928-1939.
doi: 10.1016/j.mayocp.2020.02.026. Epub 2020 Aug 6.

Hospitalization With Major Infection and Incidence of End-Stage Renal Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Junichi Ishigami  1 , Logan T Cowan  2 , Ryan T Demmer  3 , Morgan E Grams  4 , Pamela L Lutsey  3 , Josef Coresh  5 , Kunihiro Matsushita  4
Affiliations

Hospitalization With Major Infection and Incidence of End-Stage Renal Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Junichi Ishigami et al. Mayo Clin Proc. 2020 Sep.

Abstract

Objective: To evaluate whether the incidence of infectious diseases increases the long-term risk for incident end-stage renal disease (ESRD) in the general population.

Patients and methods: In 10,290 participants of the Atherosclerosis Risk in Communities Study who attended visit 4 (1996-1998), we evaluated the association of incident hospitalization with major infections (pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis) with subsequent risk for ESRD through September 30, 2015. Hospitalization with major infection was entered into multivariable Cox models as a time-varying exposure to estimate the hazard ratios.

Results: Mean age was 63 years, and of 10,290 individuals, 56% (n=5781) were women, 22% (n=2252) were black, and 7% (n=666) had an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During a median follow-up of 17.4 years, there were 2642 incident hospitalizations with major infection and 281 cases of ESRD (132 cases after hospitalization with major infection). The risk for ESRD was higher following major infection compared with while free of major infection (crude incidence rate, 10.9 vs 1.0 per 1000 person-years). In multivariable time-varying Cox analysis, hospitalization with major infection was associated with a 3.3-fold increased risk for ESRD (hazard ratio, 3.34; 95% CI, 2.56-4.37). The association was similar across pneumonia, urinary tract infection, bloodstream infection, and cellulitis and osteomyelitis, and remained significant across subgroups of age, sex, race, diabetes, history of cardiovascular disease, and chronic kidney disease.

Conclusion: Hospitalization with major infection was independently and robustly associated with subsequent risk for ESRD. Whether preventive approaches against infection have beneficial effects on kidney outcomes may deserve future investigations.

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Figures

Figure 1:
Figure 1:. Subgroup analysis for the association of major infection with incident ESRD by age, sex, race, diabetes, history of cardiovascular disease, and CKD: ARIC 1996-2015.
Model was adjusted for age, sex, race, body mass index, ever smoking, ever drink, years of education, systolic blood pressure, antihypertensive drugs, diabetes, eGFR (continuous), ACR (continuous), history of cardiovascular disease, COPD and cancer, and incidence of cardiovascular disease as a time-varying covariate. Covariates were updated when available. ESRD indicates end-stage renal disease. HR indicates hazard ratio. CVD indicates cardiovascular disease. CKD indicates chronic kidney disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
Figure 2:
Figure 2:. Kaplan Meier curves depicting the cumulative incidence of ESRD in matched cohort analysis using the incidence density sampling: ARIC 1996-2015.
The analytic sample was restricted to (A) 7,901 for major infection, (B) 3,820 for pneumonia, (C) 4,014 for urinary tract infection, (D) 2,052 for bloodstream infection, (E) 1,671 for cellulitis/osteomyelitis, and (F) 6,523 for osteoarthritis. Numbers are not equal to three times the number of events due to the inability to find matched controls. ESRD indicates end-stage renal disease.
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