Pre-existing renal disease promotes sepsis-induced acute kidney injury and worsens outcome.

Abstract:

:While it is known that risk of death from sepsis is higher in patients with pre-existing chronic kidney disease its mechanism is unknown. To study this we established a two-stage mouse model where renal disease was first induced by folic acid injection followed by sub-lethal cecal ligation and puncture to induce sepsis. Septic mice with pre-existing renal disease had significantly higher mortality, serum creatinine, vascular permeability, plasma vascular endothelial growth factor (VEGF) levels, bacteremia, serum IL-10, splenocyte apoptosis and more severe septic shock when compared to septic mice without pre-existing disease. To evaluate the contribution of vascular and immunological dysfunction, we treated the folate-septic mice with soluble Flt-1 to bind VEGF and chloroquine to reduce splenocyte apoptosis. These treatments together resulted in a significant improvement in kidney injury, hemodynamics and survival. Our study shows that the sequential mouse model mimics human sepsis frequently complicated by pre-existing renal disease and might be useful in evaluating preventive and therapeutic strategies.

journal_name

Kidney Int

journal_title

Kidney international

authors

Doi K,Leelahavanichkul A,Hu X,Sidransky KL,Zhou H,Qin Y,Eisner C,Schnermann J,Yuen PS,Star RA

doi

10.1038/ki.2008.346

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

1017-25

issue

8

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)53476-5

journal_volume

74

pub_type

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