title: Reduced production of creatinine limits its use as marker of kidney injury in sepsis.
abstract: Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA.
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Asada
authors.initials: A
authors.lastname: Leelahavanichkul
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schnermann
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002738:Chloroquine / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood*; D008297:Male; D051379:Mice; D009392:Nephrectomy; D051437:Renal Insufficiency / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000188:drug therapy
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D002738:Chloroquine; D003404:Creatinine