Reduced Production of Creatinine Limits Its Use as Marker of Kidney Injury in Sepsis

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 thi...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2009-06, Vol.20 (6), p.1217-1221
Main Authors: DOI, Kent, YUEN, Peter S. T, EISNER, Christoph, XUZHEN HU, LEELAHAVANICHKUL, Asada, SCHNERMANN, Jürgen, STAR, Robert A
Format: Article
Language:English
Subjects:
Animals
Antimalarials - therapeutic use
Bacterial diseases
Bacterial sepsis
Biological and medical sciences
Biomarkers - blood
Brief Communication
Chloroquine - therapeutic use
Creatinine - blood
Human bacterial diseases
Infectious diseases
Male
Medical sciences
Mice
Nephrectomy
Nephrology. Urinary tract diseases
Renal Insufficiency - blood
Renal Insufficiency - diagnosis
Renal Insufficiency - etiology
Sepsis - blood
Sepsis - complications
Sepsis - drug therapy
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Summary: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.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2008060617