Microvascular endothelial injury and dysfunction during ischemic acute renal failure

Sutton, Timothy A.; Fisher, Charles J.; Molitoris, Bruce A.

doi:10.1046/j.1523-1755.2002.00631.x

Cited by 502 publications

(408 citation statements)

References 111 publications

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“…Among several causes of AKI after cardiac surgery one of the most important is cellular ischemia [15], since blood pressure during cardiac surgery is often at the lower limits or even below the limits of autoregulation of the blood flow. In addition, many cardiac surgery patients may have impaired autoregulation of kidney blood flow due perioperative administration of medications.…”

Section: Discussionmentioning

confidence: 99%

Fatores de risco para lesão renal aguda após cirurgia cardíaca

Rodrigues¹,

Évora²,

Bassetto³

et al. 2009

Rev Bras Cir Cardiovasc

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Fatores de risco para lesão renal aguda após cirurgia cardíacaRisk factors for acute kidney injury after cardiac surgery Abstract Objective: The objective of the present investigation was to identify risk factors for acute kidney injury in patients with normal levels of serum creatinine who underwent coronary artery bypass graft (CABG) surgery and/or valve surgery.Methods: Data from a cohort of 769 patients, after the exclusion criteria were applied, were analyzed using bivariate analyses and binary logistic regression modeling.Results: Three hundred eighty one patients experienced CABG, 339 valve surgery and 49 went through both simultaneously. Forty six percent of the patients were female and the mean age was 57±14 years (13 to 89 years). Seventy eight patients presented renal dysfunction postoperatively (10%), of these 23% needed hemodialysis (2.4% of all patients). The mortality for the whole cohort was 10%. The overall mortality for patients experiencing postoperative renal dysfunction was 40 % (versus 7%, P<0.001), 29% for those who did not need dialysis and 67% for those who needed dialysis (P=0.004). The risk factors that were independently associated with AKI were: age (P<0.000, OR: 1.056), congestive heart failure (P=0.

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Section: Discussionmentioning

confidence: 99%

Fatores de risco para lesão renal aguda após cirurgia cardíaca

Rodrigues¹,

Évora²,

Bassetto³

et al. 2009

Rev Bras Cir Cardiovasc

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“…Exacerbation of IRI in these mice was complement dependent and was associated with C3 and MAC deposition on microvascular endothelium and with evidence of peritubular capillary thrombosis. Our results suggest that complement-mediated microvascular injury, leading to an extension phase of ATN that compounds the initial ischemic assault (17), may be an important mechanism of complement injury during renal IRI. Thus, anti-complement therapies in the setting of IRI should be directed at blocking anaphylatoxin function as well as at preventing MAC-induced endothelial injury.…”

mentioning

confidence: 91%

Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59

Yamada

Miwa

Liu

et al. 2004

The Journal of Immunology

153

135

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Renal ischemia-reperfusion injury (IRI) is a feature of ischemic acute renal failure and it impacts both short- and long-term graft survival after kidney transplantation. Complement activation has been implicated in renal IRI, but its mechanism of action is uncertain and the determinants of complement activation during IRI remain poorly understood. We engineered mice deficient in two membrane complement regulatory proteins, CD55 and CD59, and used them to investigate the role of these endogenous complement inhibitors in renal IRI. CD55-deficient (CD55−/−), but not CD59-deficient (CD59−/−), mice exhibited increased renal IRI as indicated by significantly elevated blood urea nitrogen levels, histological scores, and neutrophil infiltration. Remarkably, although CD59 deficiency alone was inconsequential, CD55/CD59 double deficiency greatly exacerbated IRI. Severe IRI in CD55−/−CD59−/− mice was accompanied by endothelial deposition of C3 and the membrane attack complex (MAC) and medullary capillary thrombosis. Complement depletion in CD55−/−CD59−/− mice with cobra venom factor prevented these effects. Thus, CD55 and CD59 act synergistically to inhibit complement-mediated renal IRI, and abrogation of their function leads to MAC-induced microvascular injury and dysfunction that may exacerbate the initial ischemic assault. Our findings suggest a rationale for anti-complement therapies aimed at preventing microvascular injury during ischemia reperfusion, and the CD55−/−CD59−/− mouse provides a useful animal model in this regard.

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“…In the CPB setting, a potential etiology of cardiac‐surgery–related AKI is ischemia/reperfusion (I/R) injury, which can result in tubular epithelial and vascular endothelial damage 6, 7, 8. α‐Melanocyte‐stimulating hormone (α‐MSH) is an endogenous hormone that inhibits inflammatory, cytotoxic, and apoptotic pathways, thus preventing renal injury caused by I/R‐induced AKI 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

McCullough

Bennett‐Guerrero

Chawla³

et al. 2016

JAHA

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BackgroundPatients undergoing cardiac surgeries with cardiopulmonary bypass (on‐pump) have a high risk for acute kidney injury (AKI). We tested ABT‐719, a novel α‐melanocyte‐stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.Methods and ResultsThis phase 2b randomized, double‐blind, placebo‐controlled trial included adult patients with stable renal function undergoing high‐risk on‐pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT‐719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72‐hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800‐, 1600‐, and 2100‐μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair‐wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.Conclusions ABT‐719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90‐day outcomes in patients after cardiac surgery.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

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Microvascular endothelial injury and dysfunction during ischemic acute renal failure

Cited by 502 publications

References 111 publications

Fatores de risco para lesão renal aguda após cirurgia cardíaca

Fatores de risco para lesão renal aguda após cirurgia cardíaca

Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

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