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Critical Care
Published in: Critical Care 5/2010

Open Access 01-10-2010 | Research

Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery

Authors: Paula Dennen, Christopher Altmann, Jonathan Kaufman, Christina L Klein, Ana Andres-Hernando, Nilesh H Ahuja, Charles L Edelstein, Melissa A Cadnapaphornchai, Angela Keniston, Sarah Faubel

Published in: Critical Care | Issue 5/2010

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Abstract

Introduction

Interleukin-6 (IL-6) is a proinflammatory cytokine that increases early in the serum of patients with acute kidney injury (AKI). The aim of this study was to determine whether urine IL-6 is an early biomarker of AKI and determine the source of urine IL-6. Numerous proteins, including cytokines, are filtered by the glomerulus and then endocytosed and metabolized by the proximal tubule. Since proximal tubule injury is a hallmark of AKI, we hypothesized that urine IL-6 would increase in AKI due to impaired proximal tubule metabolism of filtered IL-6.

Methods

Urine was collected in 25 consecutive pediatric patients undergoing cardiac bypass surgery (CPB). AKI was defined as a 50% increase in serum creatinine at 24 hours (RIFLE (Risk, Injury, Failure, Loss, End stage), R). Mouse models of AKI and freshly isolated proximal tubules were also studied.

Results

Urine IL-6 increased at six hours in patients with AKI versus no AKI (X2 = 8.1750; P < 0.0042). Urine IL-6 > 75 pg/mg identified AKI with a sensitivity of 88%. To assess whether increased urine IL-6 occurs in functional versus structural renal failure, mouse models of pre-renal azotemia after furosemide injection (no tubular injury), ischemic AKI (tubular injury) and cisplatin AKI (tubular injury) were studied. Urine IL-6 did not significantly increase in pre-renal azotemia but did increase in ischemic and cisplatin AKI. To determine if circulating IL-6 appears in the urine in AKI, recombinant human (h)IL-6 was injected intravenously and urine collected for one hour; urine hIL-6 increased in ischemic AKI, but not pre-renal azotemia. To determine the effect of AKI on circulating IL-6, serum hIL-6 was determined one hour post-intravenous injection and was increased in ischemic AKI, but not pre-renal azotemia. To directly examine IL-6 metabolism, hIL-6 was added to the media of normal and hypoxic isolated proximal tubules; hIL-6 was reduced in the media of normal versus injured hypoxic proximal tubules.

Conclusions

Urine IL-6 increases early in patients with AKI. Animal studies demonstrate that failure of proximal tubule metabolism of IL-6 results in increased serum and urine IL-6. Impaired IL-6 metabolism leading to increased serum IL-6 may contribute to the deleterious systemic effects and increased mortality associated with AKI.
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Metadata
Title
Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery
Authors
Paula Dennen
Christopher Altmann
Jonathan Kaufman
Christina L Klein
Ana Andres-Hernando
Nilesh H Ahuja
Charles L Edelstein
Melissa A Cadnapaphornchai
Angela Keniston
Sarah Faubel
Publication date
01-10-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 5/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc9289

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