A rat model of Immunologic and hypertensive kidney injury.

Abstract

Non-surgical rodent chronic kidney disease (CKD) models for both glomerular and tubular injuries are currently limited. The current study aimed to develop a rat model of CKD by combining anti-Fx1A with N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) administrations. Rats were assigned to groups receiving L-NAME, anti-Fx1A, anti-Fx1A + L-NAME, or vehicle. Renal function, stiffness, renal injury biomarkers, histopathology and renal genome-wide transcriptomic changes were evaluated. Protein and renal injury biomarker levels in urine were elevated in the anti-Fx1A alone and combination group. Shear wave elastography revealed increased stiffness of the kidneys in all treatment groups. Histopathological evaluation revealed glomerular injury, characterized by enlarged glomeruli with increased hyaline materials in both anti-Fx1A groups and tubular degeneration/regeneration in the renal cortex of all treated groups with the highest incidence and severity in the combination group. These tubular changes were sometimes accompanied by interstitial mononuclear cell infiltrates and interstitial fibrosis. Proteinuria and mild changes in blood, urine renal injury biomarkers and imaging endpoints were noted in association with these histopathologic changes. The concurrence and higher incidence and/or severity of glomerular and tubular injuries in the combination group indicates that this would be a useful and relevant CKD model suitable for mechanistic, pharmacologic and toxicologic investigations.