Cell-free hemoglobin augments acute kidney injury during experimental sepsis.

Cell-free hemoglobin augments acute kidney injury during experimental sepsis. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Shaver CM, Paul MG, Putz ND, Landstreet SR, Kuck JL, Scarfe L, Skrypnyk NI, Yang H, Harrison FE, de Caestecker MP, Bastarache JA, Ware LB Abstract Acute kidney injury is a common complication of severe sepsis and contributes to high mortality. The molecular mechanisms of acute kidney injury during sepsis are not fully understood. Because hemoproteins, including myoglobin and hemoglobin, mediate kidney injury during rhabdomyolysis, we hypothesized that cell-free hemoglobin would exacerbate acute kidney injury during sepsis. Sepsis was induced in mice by intraperitoneal injection of cecal slurry (CS). To mimic elevated levels of cell-free hemoglobin (CFH) observed during human sepsis, mice also received a retro-orbital injection of CFH or control. Four groups of mice were analyzed: sham, CFH alone, CS alone, and CS+CFH. The addition of CFH to CS reduced 48-hour survival compared to CS alone (67% vs 97%, p=0.001) and increased severity of illness. After 24 and 48 hrs, CS+CFH mice had reduced glomerular filtration rate (GFR) from baseline, while sham, CFH, and CS mice maintained baseline GFR. Biomarkers of acute kidney injury, NGAL and Kim-1, were markedly elevated in CS+CFH compared to CS (8-fold for NGAL, 2.4-fold for Kim-1, p
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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