Surgical Sepsis and Organ Crosstalk: The Role of the Kidney

Department of Surgery, The Methodist Hospital and Research Institute, Houston Texas, USA.
Journal of Surgical Research (Impact Factor: 1.94). 12/2010; 167(2):306-15. DOI: 10.1016/j.jss.2010.11.923
Source: PubMed


Acute kidney injury (AKI) is a common complication of hospitalized patients, and clinical outcomes remain poor despite advances in renal replacement therapy. The accepted pathophysiology of AKI in the setting of sepsis has evolved from one of simple decreased renal blood flow to one that involves a more complex interaction of intra-glomerular microcirculatory vasodilation combined with the local release of inflammatory mediators and apoptosis. Evidence from preclinical AKI models suggests that crosstalk occurs between kidneys and other organ systems via soluble and cellular inflammatory mediators and that this involves both the innate and adaptive immune systems. These interactions are reflected by genomic changes and abnormal rates of cellular apoptosis in distant organs including the lungs, heart, gut, liver, and central nervous system. The purpose of this article is to review the influence of AKI, particularly sepsis-associated AKI, on inter-organ crosstalk in the context of systemic inflammation and multiple organ failure (MOF).

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Available from: Frederick Alan Moore, Jul 07, 2014
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    • "Malaria and septic shock have important similarities in relation to induction of AKI [3], [14], [20]. Contrary to what was observed with sepsis, we showed a reversal of important parameters such as GFR, serum creatinine, collagen deposition, and size of interstitial space, indicating that malaria-surviving mice are less susceptible to a second kidney injury. "
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    ABSTRACT: Malaria is a worldwide disease that leads to 1 million deaths per year. Plasmodium falciparum is the species responsible for the most severe form of malaria leading to different complications. Beyond the development of cerebral malaria, impairment of renal function is a mortality indicator in infected patients. Treatment with antimalarial drugs can increase survival, however the long-term effects of malaria on renal disease, even after treatment with antimalarials, are unknown. The aim of this study was to evaluate the effect of antimalarial drug treatment on renal function in a murine model of severe malaria and then evaluate kidney susceptibility to a second renal insult. Initially, mice infected with Plasmodium berghei ANKA achieved 20% parasitemia on day 5 post infection, which was completely abolished after treatment with 25 mg/kg artesunate and 40 mg/kg mefloquine. The treatment also decreased plasma creatinine levels by 43% and partially reversed the reduction in the glomerular filtration rate induced by infection. The urinary protein/creatinine ratio, collagen deposition, and size of the interstitial space decreased by 75%, 40%, and 20%, respectively, with drugs compared with untreated infected animals. In infected-treated mice that underwent a second renal insult, the plasma creatinine level decreased by 60% and the glomerular filtration rate increased compared with infected animals treated only with antimalarials. The number of glomerular cells, collagen deposition and the size of the interstitial space decreased by 20%, 39.4%, and 41.3%, respectively, in the infected group that underwent a second renal insult compared with the infected-treated groups. These functional and structural data show that renal injury observed in a murine model of severe malaria is partially reversed after antimalarial drug treatment, making the kidney less susceptible to a second renal insult.
    PLoS ONE 04/2014; 9(4):e93634. DOI:10.1371/journal.pone.0093634 · 3.23 Impact Factor
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    • "Indeed, we often experience oliguria in the perioperative management of patients with acute generalized peritonitis due to GI perforation and ileus. This oliguria results in reduced renal perfusion due to hypovolemia caused by systemic inflammatory response syndrome [19], sepsis [20], and intra-abdominal hypertension [21]. Empirically, we treat oliguria by infusion of extracellular fluid. "
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    ABSTRACT: Purpose: We studied the effectiveness of human atrial natriuretic peptide (hANP) on management of acute kidney injury. Methods: This retrospective single-center study included 43 patients from January 2007 to February 2010 who had undergone non-elective abdominal surgery for gastrointestinal perforation and ileus. Patients were separated into 2 groups according to whether hANP was administered or not, and 4 subgroups according to whether or not baseline serum creatinine <1.2 mg/dL; normal cre/hANP (-) (n = 22), high cre/hANP (-) (n = 10), normal cre/hANP (+) (n = 4), and high cre/hANP (+) (n = 7). The administration of hANP was started during operation. Results: The administration rate of hANP ranged between 0.02 and 0.05 μg/kg per minute, except for one patient and the average postoperative administration time of hANP was 167 ± 237 h (range, 8-888 h). There were no significant differences in characteristics of patients within four subgroups, except for patient's weight. Serum creatinine in high cre/hANP (+) got to decrease more than high cre/hANP (-). Outcomes such as 28-day mortality were not significantly different among four subgroups. No patients required renal replacement therapy in each subgroup. Conclusion: Intravenous low dose of hANP was useful as acute kidney injury management in gastrointestinal perforation and ileus patients undergoing non-elective surgery.
    Journal of critical care 10/2012; 28(2). DOI:10.1016/j.jcrc.2012.07.020 · 2.00 Impact Factor
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    • "Although kidney injury occurs very frequently during sepsis, its pathophysiology is not that well understood [34,35]. Most studies have focused on alterations of perfusion whereas the role of changes in GFB structure and/or function have scarcely been investigated, even though they are likely to occur as suggested by the early appearance of albuminuria in postoperative patients who evolve to sepsis compared to those having a regular postoperative course [36]. "
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    ABSTRACT: Increased vascular permeability represents one of the hallmarks of sepsis. In the kidney, vascular permeability is strictly regulated by the 'glomerular filtration barrier' (GFB), which is comprised of glomerular endothelium, podocytes, their interposed basement membranes and the associated glycocalyx. Although it is likely that the GFB and its glycocalyx are altered during sepsis, no study has specifically addressed this issue. The aim of this study was to evaluate whether albuminuria--the hallmark of GFB perm-selectivity--occurs in the initial stage of sepsis and whether it is associated with morphological and biochemical changes of the GFB. Cecal ligation and puncture (CLP) was used to induce sepsis in the rat. Tumor necrosis factor (TNF)-alpha levels in plasma and growth of microorganisms in the peritoneal fluid were evaluated at 0, 3 and 7 hours after CLP or sham-operation. At the same times, kidney specimens were collected and structural and ultrastructural alterations in the GFB were assessed. In addition, several components of GFB-associated glycocalyx, syndecan-1, hyluronan (HA) and sialic acids were evaluated by immunofluorescence, immunohistochemistry and lectin histochemistry techniques. Serum creatinine and creatinine clearance were measured to assess kidney function and albuminuria for changes in GFB permeability. Analysis of variance followed by Tukey's multiple comparison test was used. Septic rats showed increased TNF-alpha levels and growth of microorganisms in the peritoneal fluid. Only a few renal corpuscles had major ultrastructural and structural alterations and no change in serum creatinine or creatinine clearance was observed. Contrarily, urinary albumin significantly increased after CLP and was associated with diffuse alteration in the glycocalyx of the GFB, which consisted in a decrease in syndecan-1 expression and in HA and sialic acids contents. Sialic acids were also changed in their structure, exhibiting a higher degree of acetylation. In its initial phase, sepsis is associated with a significant alteration in the composition of the GFB-associated glycocalyx, with loss of GFB perm-selectivity as documented by albumin leakage into urine.
    Critical care (London, England) 11/2011; 15(6):R277. DOI:10.1186/cc10559 · 4.48 Impact Factor
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