ORIGINAL INVESTIGATION Risk of Bloodstream Infection in Patients With Chronic Kidney Disease Not Treated With Dialysis Matthew T. James, MD; Kevin B. Laupland, MD, MSc; Marcello Tonelli, MD, SM; Braden J. Manns, MD, MSc; Bruce F. Culleton, MD, MS; Brenda R. Hemmelgarn, PhD, MD; for the Alberta Kidney Disease Network Background: Patients with end-stage renal disease re- tion, of which most (75%) were community-onset infec- quiring dialysis are at high risk for bloodstream infec- tions. Compared with patients with an eGFR of 60 mL/ tion and infection-related death. Whether patients with min/1.73 m2 or higher, adjusted hazard ratios (95% chronic kidney disease who are not receiving dialysis are confidence intervals) for bloodstream infection accord- also at increased risk of bloodstream infection is less clear. ing to eGFR were, respectively, 1.24 (1.01-1.52), 1.59 (1.24-2.04), and 3.54 (2.69-4.69) in those with an eGFR Methods: We examined the association between chronic of 45 to 59, 30 to 44, and less than 30 mL/min/1.73 m2. kidney disease not being treated with dialysis and blood- The associations were consistent for both community- stream infection in a cohort of patients 66 years or older. onset and nosocomial infections. Compared with pa- All patients required at least 1 outpatient serum creati- tients with an eGFR of 60 mL/min/1.73 m2 or higher, the nine measurement enabling estimation of glomerular fil- risk of death within 30 days of community-onset blood- tration rate (eGFR) using the Modification of Diet in Re- stream infection was significantly greater in those with nal Disease Study equation. Cox proportional hazards an eGFR less than 30 mL/min/1.73 m2 (hazard ratio, 4.10; models with censoring at the initiation of renal replace- 95% confidence interval, 2.06-8.14). ment therapy or death were used to determine associa- tions between eGFR, bloodstream infection, and death Conclusion: Older adults with chronic kidney disease within 30 days of community-onset bloodstream infec- not being treated with dialysis are at increased risk of tion, adjusting for potential confounders. bloodstream infection and of death following community- onset bloodstream infection. Results: In 25 675 patients followed up for a median of 3.2 years, 797 developed at least 1 bloodstream infec- Arch Intern Med. 2008;168(21):2333-2339 HRONIC KIDNEY DISEASE disease (ESRD) requiring dialysis.8,9 The (CKD), defined by an es- high rate of bloodstream infection in pa- timated glomerular filtra- tients receiving hemodialysis is attribut- tion rate (eGFR) less than able in part to the requirement for vascu- 60 mL/min/1.73 m2 or evi- lar access.10,11 While not as high as in Cdence of structural kidney damage, affects patients receiving dialysis, reported rates at least 20% of adults 65 years or older and of hospitalization because of septicemia in has been independently associated with patients with CKD not being treated with hospitalization and death.1,2 The excess risk dialysis seem to be 3- to 4-fold greater than of morbidity and mortality in patients with in patients without CKD.12 However, it is CKD is largely attributable to cardiovascu- unclear whether this observation is attrib- lar events3,4; however, recent cohort stud- utable to the consequences of CKD or ex- ies have suggested that CKD is also a risk plained by the older age and greater bur- factor for noncardiovascular morbidity and den of comorbidities in patients with CKD. Author Affiliations are listed at mortality5 including that caused by infec- We sought to determine the associa- the end of this article. 6,7 Group Information: A list of tion. Few studies have investigated asso- tion between CKD not treated with dialy- the Alberta Kidney Disease ciations between CKD and specific infec- sis and bloodstream infection in a large Network appears at tious conditions. community-based cohort of older adults. http://www.akdn.info Bacteremia is the second leading cause Cognizant that an increased rate of hos- /contact.html. of death in patients with end-stage renal pitalization for patients with CKD could (REPRINTED) ARCH INTERN MED/ VOL 168 (NO. 21), NOV 24, 2008 WWW.ARCHINTERNMED.COM 2333 ©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 explain increased rates of bloodstream infection from cocci, viridans group streptococci, and Bacillus, Corynebacte- nosocomial infections alone, we also analyzed community- rium, or Propionibacterium species) were excluded from the onset and nosocomial bloodstream infection as separate primary analysis because of the difficulty in establishing their 13,19 outcomes.13 We hypothesized that patients with a lower clinical significance. Further analyses were also performed eGFR would be more likely than patients with pre- by subdividing first bloodstream infection into community- onset or nosocomial bloodstream infection. Infections were de- served renal function to develop bloodstream infection, fined as community-onset if submitted from community-based independent of age or comorbidities. collection sites or identified within the first 2 days of admission to an acute care facility13 and as nosocomial if identified after 2 days METHODS of admission to an acute care facility. The secondary outcome of interest was death within 30 days of community-onset blood- STUDY POPULATION stream infection, with date of death determined by linkage to the Alberta Bureau of Vital Statistics, which maintains records of deaths of all residents of the province of Alberta. Patients were The cohort included all adults 66 years or older with at least 1 followed up to December 31, 2004, for all outcomes, with cen- outpatient serum creatinine measurement between July 1, 2001, soring at date of death or initiation of renal replacement therapy. and December 31, 2001, as identified from the Calgary Labora- Emigration from the Calgary Health Region was not identified; tory Services database in Calgary, Alberta, Canada. Calgary Labo- however, the 2002-2003 population estimates for emigration from ratory Services provides testing for the entire Calgary Health Re- Calgary of less than 2%20 were not expected to bias results. gion (catchment population, 1.1 million, with 80 567 subjects 66 years or older in 2001) using a single regional laboratory and standardized methods that are routinely recalibrated against ref- COVARIATES erence standards. To avert classifying episodes of acute renal fail- ure as CKD, laboratory measurements associated with a hospi- The cohort was linked to provincial administrative data to ob- tal admission were excluded. Patients were excluded if they were tain a measure of comorbidity based on prescription drug use receiving renal replacement therapy (hemodialysis, peritoneal in the 6 months before the index serum creatinine concentra- dialysis, or kidney transplantation) at study enrollment or if the tion as determined by the Chronic Disease Score, which is a baseline estimate of kidney function was clinically implausible validated index weighted on patterns of drug use, with higher (eGFR Ͼ150 mL/min/1.73 m2; n=80). scores reflecting increased comorbidity.21 Prescription drug use was also used to define the presence of diabetes mellitus, de- MEASUREMENT OF KIDNEY FUNCTION fined as at least 1 prescription for insulin or an oral hypogly- cemic agent in the year before cohort entry. Hemoglobin and The GFR for each patient was estimated using the abbreviated albumin measurements were obtained from the Calgary Labo- Modification of Diet in Renal Disease Study equation ratory Services database. Although unavailable for all patients, (eGFR=186ϫplasma creatinine−1.154ϫage−0.203ϫ0.742 [if during the study, hemoglobin levels were determined in 17 979 female]).14 Black race was omitted from the equation because patients (70% of the cohort), and serum albumin levels in 5493 this variable was unavailable in the data source, although this patients (21%). Linkage to the Southern Alberta Renal Pro- is unlikely to bias results because less than 1% of the popula- gram database was performed to determine whether patients 22 tion of Calgary is black.15 Serum creatinine measurements were were receiving care in a dedicated CKD clinic and to exclude analyzed in a single laboratory, eliminating the potential for patients receiving renal replacement therapy at study enroll- interlaboratory measurement variation. We have previously re- ment. The Southern Alberta Renal Program provides ESRD care ported indirect calibration of eGFR results for this laboratory to all patients within the Calgary Health Region and maintains using an isotope dilution mass spectrometry reference stan- computerized records of all patients receiving dialysis, renal 23 dard and the modified Modification of Diet in Renal Disease transplantation, or nondialysis CKD care. Study equation,16 with valid estimates obtained.17 Further- more, we have observed minimal intralaboratory variation in STATISTICAL ANALYSES eGFR over time in our setting, as previously described.18 We used the first eGFR determined during the study entry period Baseline characteristics according to eGFR were summarized as to define baseline kidney function. mean and standard deviation for normally distributed continu- ous variables, percent prevalence for dichotomous variables, and OUTCOMES median with interquartile range for variables with a nonnormal distribution. Differences in baseline characteristics according to The primary outcome of interest was first bloodstream infec- eGFR were