Massive chemokine transcription in acute renal failure due to polymicrobial sepsis

Abdominal sepsis and septic shock are still major causes of mortality in in tensive care units (ICU). Acute renal failure (ARF) is one of the hallmarks encountered in septic shock. The pathophysiological alterations leading to ARF are poorly understood. A novel murine model of polymicrobial sepsis (c o[on ascendens stent peritonitis [CASP] was used to investigate functional renal parameters, renal chemokine transcription levels, and recruitment of inflammatory leukocytes in septic ARF. GASP was induced by inserting a 14-g auge stent into the colon ascendens of C57BL/6 mice, generating a septic fo cus resulting in polymicrobial sepsis, Mice were monitored for urine output and serum azotemia. Kidneys were harvested for analysis of leukocyte infil tration by immunohistochemistry and chemokine gene expression by RNase prot ection assay (3, 6, 12, and 18 h). GASP, but not sham-CASP, resulted in anu ria immediately after surgery and in elevated serum creatinine and BUN dete cted 18 h after GASP surgery, confirming acute renal failure. Progressive i nduction of chemokine gene expression was observed for [P-IO, MIP-2, MIP-1 alpha, MIP-1 beta, MCP-1, and RANTES peaking at 12 h with subsequent decrea se. Immunohistochemistry revealed an accumulation of neutrophils and monocy tes which had adhered to the renal vascular endothelium. Thus, acute renal failure in sepsis is accompanied by a marked upregulation of chemokines of the CC and CXC group within the kidney.