Background: Infection, bacteremia and sepsis are major sources of morbidity and mortality in patients with end-stage renal disease. This study sought to determine the association between predialysis chronic kidney disease (CKD) and infection-related mortality. Methods: We analyzed participants in the Third National Health and Nutrition Examination Survey (NHANES III). The study included adults ≧45- years-old without end-stage renal disease. Estimated glomerular filtration rate (eGFR) was categorized as ≧60, 45–59.9 and <45 ml/min per 1.73 m2, and urinary albumin-to-creatinine ratio (ACR) as <30, 30–299.9 and ≧300 mg/g. The study identified infection-related mortality, including septicemia, respiratory, abdominal and gastrointestinal, cardiac, kidney and genitourinary, neurologic, and other infections over a median of 13 years using the National Death Index. Results: Of 7,400 participants included in the study, 206 died from infections. Compared to individuals with eGFR ≧60 ml/min per 1.73 m2, infection-related mortality was higher for those with lower eGFR [adjusted HR = 1.36 (95% CI: 0.81, 2.30) and 2.36 (1.04, 5.38) for eGFR of 45–59.9 and <45 ml/min per 1.73 m2, respectively; p trend = 0.06]. Compared to individuals with ACR <30 mg/g, infection-related mortality was higher for ACR levels of 30–299 and ≧300 mg/g [adjusted HR = 1.68 (95% CI: 0.97, 2.92) and 2.84 (0.92, 8.74), p trend = 0.02]. Conclusions: Reduced eGFR and albuminuria are associated with increased risk for infection-related mortality. Efforts are needed to reduce its incidence and mitigate the effects of infections among individuals with CKD.

Keywords:
Chronic kidney disease, Infection, Sepsis, Mortality
1.
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS: Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038–2047.
2.
James MT, Hemmelgarn BR, Tonelli M: Early recognition and prevention of chronic kidney disease. Lancet 2010;375:1296–1309.
3.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–1305.
4.
Warnock DG, Muntner P, McCullough PA, Zhang X, McClure LA, Zakai N, Cushman M, Newsome BB, Kewalramani R, Steffes MW, Howard G, McClellan WM: Kidney function, albuminuria, and all-cause mortality in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Am J Kidney Dis 2010;56:861–871.
5.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296–327.
6.
Sarnak MJ, Jaber BL: Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 2000;58:1758–1764.
7.
Powe NR, Jaar B, Furth SL, Hermann J, Briggs W: Septicemia in dialysis patients: Incidence, risk factors, and prognosis. Kidney Int 1999;55:1081–1090.
8.
Kahn JM, Goss CH, Heagerty PJ, Kramer AA, O’Brien CR, Rubenfeld GD: Hospital volume and the outcomes of mechanical ventilation. N Engl J Med 2006;355:41–50.
9.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions conference. Intensive Care Med 2003;29:530–538.
10.
Selvin E, Manzi J, Stevens LA, Van Lente F, Lacher DA, Levey AS, Coresh J: Calibration of serum creatinine in the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004. Am J Kidney Dis 2007;50:918–926.
11.
Levey AS, Stevens LA: Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 2010;55:622–627.
12.
Loria CM, Sempos CT, Vuong C: Plan and operation of the NHANES II Mortality Study, 1992. Vital Health Stat 1999;38:1–16.
13.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303–1310.
14.
Wang HE, Devereaux RS, Yealy DM, Safford MM, Howard G: National variation in United States sepsis mortality: a descriptive study. Int J Health Geogr 2010;9:9.
15.
Hoen B, Paul-Dauphin A, Hestin D, Kessler M: EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol 1998;9:869–876.
16.
James MT, Laupland KB, Tonelli M, Manns BJ, Culleton BF, Hemmelgarn BR: Risk of bloodstream infection in patients with chronic kidney disease not treated with dialysis. Arch Int Med 2008;168:2333–2339.
17.
Hallan S, Astor B, Romundstad S, Aasarod K, Kvenild K, Coresh J: Association of kidney function and albuminuria with cardiovascular mortality in older versus younger individuals: The HUNT II study. Arch Int Med 2007;167:2490–2496.
18.
Aird WC: Sepsis and coagulation. Crit Care Clin 2005;21:417–431.
19.
Mathieu P, Poirier P, Pibarot P, Lemieux I, Despres JP: Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease. Hypertension 2009;53:577–584.
20.
Schuetz P, Yano K, Sorasaki M, Ngo L, St Hilaire M, Lucas JM, Aird W, Shapiro NI: Influence of diabetes on endothelial cell response during sepsis. Diabetologia 2011;54:996–1003.
21.
Vachharajani V, Vital S: Obesity and sepsis. J Intensive Care Med 2006;21:287–295.
22.
Landgarten MJ, Kumar A, Parrillo JE: Cardiovascular dysfunction in sepsis and septic shock. Curr Treat Options Cardiovasc Med 2000;2:451–459.
23.
Gupta R, Plantinga LC, Fink NE, Melamed ML, Coresh J, Fox CS, Levin NW, Powe NR: Statin use and sepsis events in patients with chronic kidney disease. JAMA 2007;297:1455–1464.
24.
Plantinga LC, Tuot DS, Powe NR: Awareness of chronic kidney disease among patients and providers. Adv Chronic Kidney Dis 2010;17:225–236.
25.
McClellan WM, Newsome BB, McClure LA, Cushman M, Howard G, Audhya P, Abramson JL, Warnock DG: Chronic kidney disease is often unrecognized among patients with coronary heart disease: the REGARDS cohort study. Am J Nephrol 2009;29:10–17.
26.
Williams BC, Demitrack LB, Fries BE: The accuracy of the National Death Index when personal identifiers other than social security number are used. Am J Public Health 1992;82:1145–1147.
27.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS: Prevalence of chronic kidney disease and decreased kidney function in the adult us population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41:1–12.
© 2011 S. Karger AG, Basel
2011
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