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Increased renal expression and urinary excretion of TLR 4 in acute kidney injury associated with cirrhosis
Author(s) -
Shah Naina,
Mohamed Fatma E.,
JoverCobos Maria,
Macnaughtan Jane,
Davies Nathan,
Moreau Richard,
Paradis Valerie,
Moore Kevin,
Mookerjee Raj,
Jalan Rajiv
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12047
Subject(s) - cirrhosis , medicine , acute kidney injury , urinary system , kidney , creatinine , biomarker , gastroenterology , hepatorenal syndrome , kidney disease , alcoholic liver disease , acute tubular necrosis , pathology , biology , biochemistry
Background Patients with cirrhosis frequently develop renal dysfunction, a proportion of who do not fulfill criteria for hepatorenal syndrome ( HRS ). We hypothesized that the kidneys in these patients would exhibit histological and biomarker evidence of kidney injury. We looked specifically for TLR expression as they may mediate kidney injury. Methods Sixty seven subjects (6); alcoholic cirrhosis: compensated (9), acute deterioration of alcoholic cirrhosis (52)] were included. Renal dysfunction was defined as a creatinine of >133 μmol/L and/or according to the AKI network criteria. Urinary biomarkers, KIM ‐1, π GST , α GST and a novel biomarker, urinary TLR 4 were measured. Renal biopsies were also available from eight other alcoholic cirrhosis patients (three non‐ HRS renal dysfunction; five HRS ) that were stained for TLR 4 and caspase‐3. Results Fourteen patients developed renal dysfunction, amongst these three had type 2 HRS . KIM ‐1, π GST and α GST were higher in patients with acute deterioration of cirrhosis compared with patients with compensated cirrhosis, but did not differ between those with and without renal dysfunction. Urinary TLR 4 was significantly higher in patients with renal dysfunction associated with infection/inflammation. Kidney biopsies from non‐ HRS renal dysfunction patients showed tubular damage with evidence of increased tubular expression of TLR 4, and caspase‐3. Minor changes were observed in HRS patients. Conclusions The data provide proof of concept that renal dysfunction in patients with cirrhosis with superimposed inflammation is associated with significant tubular injury and apoptosis and with increased renal expression and urinary excretion of the TLR 4, suggesting a potential role of TLR 4 as mediator of renal injury.