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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Acute Kidney Injury, Animals, Ischemia, Kidney, Male, Rats, Rats, Sprague-Dawley, Recombinant Proteins, Thrombomodulin.
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Does intrarenal administration of recombinant human soluble thrombomodulin ameliorate ischaemic acute renal failure? Context: Thrombomodulin (TM) is an endothelial anti-coagulant cofactor which also has anti-inflammatory properties. The present study was performed to investigate the effects of recombinant human soluble TM (RHS-TM) on ischaemia/reperfusion (I/R) renal injury. A right nephrectomy was performed in rats, and the left kidney was filled with RHS-TM (0.25 mg/kg), argatroban (20 mg/kg) or a vehicle for 45 min. Before reperfusion, the fluid trapped in the kidney was completely removed. At 24 h after I/R, renal cortical blood flow was measured using a CCD video camera, and the kidneys were harvested for the study. Next, cultured human umbilical vein endothelial cells were treated with RHS-TM (2, 10 or 50 mg/ml) or a vehicle, and incubated for 5 h in culture medium containing 300 microM hydrogen peroxide. Apoptotic cell death was analysed by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Immunohistochemistry revealed that the level of TM expression decreased in rat kidneys after I/R. RHS-TM significantly decreased blood urea nitrogen and serum creatinine levels. It also prevented a reduction in cortical blood flow, and attenuated tubular damage and macrophage/neutrophil infiltration. In addition, the number of TUNEL-positive cells decreased significantly in rats treated with RHS-TM. In contrast, argatroban, an inhibitor of thrombin did not show significant renoprotective actions. The results of in vitro study showed that RHS-TM significantly suppressed the number of apoptotic cells.
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The transient intrarenal administration of RHS-TM, but not argatroban, to the kidney attenuates I/R renal injury. The present study suggests that RHS-TM would be a useful tool in preventing transplanted kidney damage or treating acute renal failure in the clinical setting. Final Decision: yes