SP289HYPERTENSION AGGRAVATES ACUTE KIDNEY INJURY (AKI) AND ACCELERATES PROGRESSION TO CHRONIC KIDNEY DISEASE (CKD) IN CD1 MICE

Abstract

Introduction and Aims: Acute kidney injury (AKI) is a frequent complication after major cardiac surgery and solid organ transplantation. AKI can be complicated by hypertension due to activation of the RAAS system . However, the most frequently used laboratory mouse strain (C57Bl/6) lacks blood pressure elevation after renal injury. In this study we provide evidence that hypertension aggravates post-ischemic AKI and accelerates progression to chronic kidney disease (CKD) in CD1 mice. Methods: IRI was induced by transient clamping of the renal pedicles for 35 minutes in CD1 compared to C57Bl/6 mice. Survival, renal function (creatinine, BUN), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by inulin/ PAH-clearance and renal perfusion impairment was assessed by functional magnetic resonance imaging (MRI). Systemic blood pressure was measured by a tail cuff method at different time points after IRI. Morphological changes were investigated by Masson Goldner staining and immunohistochemistry for inflammation (myeloid cell infiltration) and fibrosis (collagen and fibronectin expression). In addition, silver stain was done to quantify mesangial matrix expansion. Results: Renal function impairment after IRI was similar in CD1 and C57Bl/6 mice but only the CD1 mice developed severe blood pressure elevation (+20 mmHg) within 2 weeks. Functional MRI revealed long lasting impairment of renal perfusion in CD1 mice and markedly better recovery in C57Bl/6 mice. Similar results were obtained by PAH clearance measurements. Histologically, AKI score and inflammation was similar at day 1 after IRI in both mouth strains. Within 14 days after IRI CD1 mice developed severe tubulo interstitial fibrosis with marked elevation of fibronectin and collagen expression. In contrast, C57Bl/6 recovered and had only mild focal cortical scaring after 14 days. Silver stain revealed significant mesangial matrix expansion only in CD1 mice correlating with accelerated glomerulosclerosis. Conclusions: CD1 mice show severe blood pressure elevation in ischemia induced AKI which accelerates the progression to CKD.