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Time‐dependent serum, urinary and tissue biomarker responses to renal ischemia/reperfusion injury in rats (1134.13)
Author(s) -
Richards Toni,
Glascock Christopher,
Horn Todd,
McFarland Kelli,
Plato Craig
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1134.13
Subject(s) - creatinine , medicine , renal function , kidney , acute kidney injury , urinary system , ischemia , acute tubular necrosis , renal ischemia , biomarker , endocrinology , urology , reperfusion injury , pathology , chemistry , biochemistry
Acute kidney injury (AKI) secondary to acute renal ischemia is associated with high mortality and morbidity with few effective treatments. To elucidate potential novel therapeutic targets, the current study sought to characterize the acute serum, urinary and tissue biomarker response profiles to discrete durations of renal ischemia/reperfusion (I/R)‐induced AKI in rats. At d0, rats underwent sham (n=4) or warm, bilateral renal I/R (n=8/group; 30’ or 40’ ischemia) surgery using our proprietary vascular clamp. Rats were single‐housed in metabolic cages for balance of study (24 or 48 hrs post‐reperfusion). In 24 hr intervals post‐reperfusion, urine volumes were determined and sampled, and serum was collected. Clinical chemistry and ELISAs were applied to urine and serum analyses. At endpoint, renal tissue was collected for analysis of mRNA expression (quantitated via Luminex) and ED1+ immunohistochemistry. I/R injury elicited perturbations in multiple indices of renal function compared to sham rats including increased renal mass, serum BUN and creatinine (30’: 4.1±1.2 fold; 40’: 10.8±1.5 fold at 48 hr), urinary protein:, albumin:, Kim‐1: (30’: 131.4 fold; 40’: 60.4 fold at 48 hr), and MCP‐1:creatinine (30’: 10.4 fold; 40’: 86.6 fold at 24 hr), and decreased creatinine clearance (30’: ‐76%; 40’: ‐95% at 48 hr),. I/R injury altered tissue mRNA expression of several biomarkers (pro‐inflammatory, pro‐fibrotic, pro‐ and anti‐oxidative stress, tissue remodeling, apoptosis, angiotensin II receptor, endothelin receptor) and increased renal macrophage infiltration. The biomarker expression profile was dependent on both ischemia and reperfusion durations. The distinct biomarker expression profiles of varying durations of renal I/R in rats can subsequently be utilized to define potential therapeutic targets and possible new AKI diagnostic markers.