Egfr and the Risk of Community-Acquired Infections
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CJASN ePress. Published on August 17, 2017 as doi: 10.2215/CJN.00250117 Article eGFR and the Risk of Community-Acquired Infections | | Hong Xu,*† Alessandro Gasparini,†‡ Junichi Ishigami,§ Khaled Mzayen, Guobin Su, ¶ Peter Barany,† Johan A¨rnlo¨v,**†† Bengt Lindholm,† Carl Gustaf Elinder,† Kunihiro Matsushita,§ and Juan Jesu´s Carrero*† Abstract Background and objectives Community-acquired infections are common, contributing to adverse outcomes and increased health care costs. We hypothesized that, with lower eGFR, the incidence of community-acquired infections increases, whereas the pattern of site-specific infections varies. Departments of 6 *Medical Epidemiology Design,setting, participants,&measurementsAmong 1,139,470health careusers(meanage =52 18 years old, 53% and Biostatistics and | women) from the Stockholm CREAtinine Measurements Project, we quantified the associations of eGFR with the Public Health † risk of infections, overall and major types, over 12 months. Sciences and Division of Renal Medicine and Baxter Novum, ResultsA total of 106,807 counts of infections were recorded throughout 1,128,313 person-years. The incidence rate Department of Clinical of all infections increased with lower eGFR from 74/1000 person-years for individuals with eGFR=90–104 ml/min Science, Intervention per 1.73 m2 to 419/1000 person-years for individuals with eGFR,30 ml/min per 1.73 m2.ComparedwitheGFRof and Technology, 90–104 ml/min per 1.73 m2, the adjusted incidence rate ratios of community-acquired infections were 1.08 (95% Karolinska Institutet, fi – 2 fi Stockholm, Sweden; con dence interval, 1.01 to 1.14) for eGFR of 30 59 ml/min per 1.73 m and 1.53 (95% con dence interval, 1.39 to ‡Department of Health , 2 1.69) for eGFR 30 ml/min per 1.73 m . The relative proportions of lower respiratory tract infection, urinary tract Sciences, University of infection, and sepsis became increasingly higher along with lower eGFR strata (e.g., low respiratory tract infection Leicester, Leicester, , – 2 United Kingdom; accounting for 25% versus 15% of community-acquired infections in eGFR 30 versus 90 104 ml/min per 1.73 m , § respectively). Differences in incidence associated with eGFR were in general consistent for most infection types, Department of Epidemiology, Johns except for nervous system and upper respiratory tract infections, for which no association was observed. Hopkins Bloomberg School of Public Conclusions This region-representative health care study finds an excess community-acquired infections Health, Baltimore, incidence in individuals with mild to severe CKD. Lower respiratory tract infection, urinary tract infection, and Maryland; ¶Department of sepsis are major infections in CKD. Nephrology, Clin J Am Soc Nephrol 12: ccc–ccc, 2017. doi: https://doi.org/10.2215/CJN.00250117 Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Introduction would inform health care policymakers about appropri- Medicine, Guangzhou CKD is common, with a population prevalence of 5%– ate prevention strategies and health service planning in City, Guangdong 15% in most developed countries (1,2), and it is Province, China; the context of CKD. In this study, we hypothesized **School of Health and associated with a markedly increased risk of death that, with lower eGFR, the incidence of community- Social Studies, Dalarna and hospitalizations (3,4). Infections are probably the acquired infections increases, whereas the pattern of University, Falun, most significant and serious noncardiovascular compli- fi Sweden; and speci cinfectionsvaries. †† cations among persons with CKD (https://www.usrds. Department of Medical Sciences, org/adr.aspx) (5). Decreased kidney function leads to Uppsala University retention of metabolic waste products and alteration of Materials and Methods Hospital, Uppsala, multiple pathways, including the immune system (6). Study Population Sweden In patients undergoing dialysis, the risks of fatal We used data from the Stockholm CREAtinine and nonfatal infections are markedly high (7–9), and a Measurements (SCREAM) Project (2,19). Briefly, the Correspondence: few studies have shown that mildly to moderately SCREAM Project is a health care utilization cohort Dr. Juan Jesu´s Carrero, Department of Medical decreased kidney function is also associated with from the region of Stockholm, Sweden, and it includes Epidemiology and increased risk of infections (10–15). However, almost all residents who undertook at least one measurement Biostatistics (MEB), all of these studies focus on mortality or hospitaliza- of serum creatinine in ambulatory or hospital care Karolinska Institutet, tion due to infections, including both nosocomial and during 2006–2011. Creatinine and other laboratory Nobels va¨g 12A, Box community acquired (10–15). data were linked with regional and national admin- 281, 171 77 Stockholm, Sweden. Community-acquired infections account for consid- istrative databases for information on health care Email: juan.jesus. erable morbidity and mortality as well as substantial utilization, dispensed drugs, validated RRT end [email protected] health care costs worldwide (16–18), but a compre- points, and follow-up for death, with virtually no or hensive analysis on the risk of infections and possible minimal loss to follow-up. Given the commonness of differences in their proportions across the full spec- creatinine testing, the SCREAM Project captured 66% trum of kidney function is lacking. Such an analysis of the complete population census of the region, www.cjasn.org Vol 12 September, 2017 Copyright © 2017 by the American Society of Nephrology 1 2 Clinical Journal of the American Society of Nephrology including .75% of individuals above the age of 45 years old this follow-up to reduce possible misclassification bias and (19). For this study, index date was determined by the first assumed that eGFR remained stable during this short period. available serum creatinine measurement of any adult (.18 The primary outcome was the overall incidence of community- years old) (Supplemental Figure 1). Exclusion criteria were acquired infections, includingupperandlowerrespiratory creatinine measurement during a hospital stay, pregnancy tract infections, gastrointestinal tract infections, urinary tract (defined by the presence of an International Classification of infections (UTIs), skin/soft tissue infections, nervous system Disease, 10th Revision, Clinical Modification [ICD-10] infections, sepsis, musculoskeletal system infections, and code among Z321, Z33–Z38, and any O code in the cardiovascular system infections (Supplemental Table 1) di- preceding 6 months), presence of chronic infections (in- agnosed in health care (at primary care, outpatient specialist cluding HIV; ICD-10 codes B15–B19, B20–B24, and A15– consultation, or primary hospitalization diagnosis). The sec- A19), or undergoing RRT (dialysis or history of kidney ondary outcome was the incidence of type-specificinfections. transplantation as ascertained by linkage with the Swedish To avoid overestimation from repeated attendance for the Renal Registry (http://www.medscinet.net/snr/) (Supplemental same infection, repeated diagnostic codes recorded within 28 Material). To avoid selecting creatinine values that may be days of one another were attributed to a single episode of determined by preexisting infections, we excluded serum infection, and the date of appearance of the first code was creatinine measurements with a diagnosis of infection during selected as the event date. We further excluded infections the preceding 3 months (definitions of infection are likely to be acquired in hospital, which encompassed post- in Supplemental Table 1). surgical infections, central line–associated bloodstream in- fections, catheter-associated UTIs, and ventilator-associated Exposure and Covariates pneumonia ICD-10 diagnoses (a list of excluded codes is The exposure was eGFR calculated from serum creati- detailed in Supplemental Table 3); in addition, infections nine using the 2009 Chronic Kidney Disease Epidemiology diagnosed in the 14 days after a hospital discharge were also Collaboration equation (20). All creatinine measurements considered hospital-acquired infections and excluded. were standardized to isotope dilution mass spectrometry standards. Although data for ethnicity were not available Data Analyses fi by law, misclassi cation of eGFR is expected to be minimal, We present descriptive values as mean and SD or count because the vast majority of the residents of the Stockholm with proportion. We calculated crude incidence rates with region are of white origin (21). Five categories of eGFR 95% confidence intervals (95% CIs) using the exact method $ – – – , were studied: eGFR 105, 90 104, 60 89, 30 59, and 30 and adjusted incidence rates and incidence rates ratios (IRRs) 2 – ml/min per 1.73 m , with eGFR of 90 104 ml/min per using a zero-inflated negative binomial model to account for 1.73 m2 serving as the reference group for consistency overdispersion and excess zero counts. We also included an with a previous publication in a comparable health care offset term in the model to account for time at risk. Covariates extraction from Canada (11) and because this range included in the model were age in categories; sex; and use of showed the lowest risk of the study outcome. immunosuppressive medication, antibiotics, antimycotics, fi fi Other covariates were de ned at index date of the rst and antivirals as well as the abovementioned comorbidities. recorded serum creatinine measurement