Renal histopathology during experimental septic acute kidney injury and recovery

Langenberg, Christoph, Gobe, Glenda, Hood, Sally, May, Clive N. and Bellomo, Rinaldo (2014) Renal histopathology during experimental septic acute kidney injury and recovery. Critical Care Medicine, 42 1: E58-E67. doi:10.1097/CCM.0b013e3182a639da

Author Langenberg, Christoph
Gobe, Glenda
Hood, Sally
May, Clive N.
Bellomo, Rinaldo
Title Renal histopathology during experimental septic acute kidney injury and recovery
Journal name Critical Care Medicine   Check publisher's open access policy
ISSN 0090-3493
Publication date 2014-01
Year available 2014
Sub-type Article (original research)
DOI 10.1097/CCM.0b013e3182a639da
Open Access Status
Volume 42
Issue 1
Start page E58
End page E67
Total pages 10
Place of publication Baltimore, United States
Publisher Lippincott Williams & Wilkins
Collection year 2015
Language eng
Formatted abstract
OBJECTIVES:: Our understanding of septic acute kidney injury is limited. We therefore assessed renal histopathological changes induced by septic acute kidney injury and their evolution during recovery.

DESIGN:: Prospective experimental study.

SETTING:: Physiology Research Institute.

SUBJECTS:: Twenty-two Merino sheep.

INTERVENTION:: We induced septic acute kidney injury by continuous IV infusion of Escherichia coli. We studied histology, immunohistochemistry, markers of apoptosis, and expression of nitric oxide synthase isoforms and hypoxia-inducible factor-1α. Analysis was performed on kidneys from normal sheep, sheep with septic acute kidney injury, and sheep after recovery from septic acute kidney injury.

MEASUREMENTS AND MAIN RESULTS:: In normal, septic, and recovery sheep, respectively, serum creatinine was (median) 82 (interquartile range, 70-85), 289 (171-477), and 70 (51-91) μmol/L and renal blood flow was 270 ± 42, 653 ± 210, and 250 ± 49 mL/min. There were no histological differences between baseline, acute kidney injury, and recovery sheep. There was no evidence of macrophage or myofibroblast infiltration, no evidence of caspase-3 cleavage to suggest activation of apoptotic pathways, and no increase in neutrophil gelatinase-associated lipocalin to suggest tubular injury. Similarly, quantification of apoptosis revealed no differences between the normal and septic groups (normal: median, 3; interquartile range, 0-5 cells per visual field and septic acute kidney injury: median, 3.5; interquartile range, 0-8 cells per visual field; p = 0.618), but in the recovery group, there was increased apoptosis (median, 14; interquartile range, 4-34 cells per visual field; p = 0.002). Expression of all nitric oxide synthase subtypes increased significantly in the renal cortex during septic acute kidney injury but tended to decrease in the medulla. Medullary hypoxia-inducible factor gene expression decreased from 1.00 (95% CI, 0.74-1.36) to 0.26 (95% CI, 0.09-0.76) in recovery (p = 0.0106). Both inducible nitric oxide synthase and neuronal nitric oxide synthase expressions correlated with renal blood flow.

CONCLUSION:: The lack of any tubular injury or increased apoptosis, the increased expression of all cortical nitric oxide synthase isoforms, and the link between inducible nitric oxide synthase and neuronal nitric oxide synthase with renal blood flow suggest in this experimental model that severe sepsis acute kidney injury can develop in the absence of histological or immunohistological changes and may be functional in nature.
Keyword Acute kidney injury
Nitric oxide synthase
Renal blood flow
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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