Fast Detection of Renal Ischemia in Transplanted Kidneys With Delayed Graft Function—An Experimental Study

Keller, Anna Krarup; Jørgensen, Troels Munch; Vittrup, Dorthe M.; Kjerkegaard, Ulrik Knap; Jespersen, Bente; Krag, Susanne; Bibby, Bo Martin; Stolle, Lars Bjørn

doi:10.1097/tp.0b013e318276a1c8

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…Approximately 50-70% of the mortality occurs in ARF patients in intensive care who require dialysis and among postoperative patients, 25-100% of them suffer from ARF. Regarding renal transplantation, renal IRI may elicit acute posttransplant tubular necrosis [85][86][87][88] and delayed graft function [89,90]. Reperfusion provokes inflammation by the activation of enzymes and chemical mediators, such as prostaglandins, leukotrienes, lysozymes, phospholipase A2, and ROS, in renal IRI.…”

Section: Renal Irimentioning

confidence: 99%

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

Fujino

Nishio

Ito

et al. 2016

International Immunopharmacology

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5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy.

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Section: Renal Irimentioning

confidence: 99%

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

Fujino

Nishio

Ito

et al. 2016

International Immunopharmacology

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“…The mortality rate of ARF remains between 50% and 70% among patients who receive intensive care who require dialysis and ranges between 25% and 100% in postoperative patients suffering from ARF. Renal IRI is unavoidable in renal transplantation and may lead to acute posttransplant tubular necrosis (21,24,49,55) and delayed graft function (27,47). Recent findings have indicated that carbon monoxide (CO), an endogenous byproduct of heme degradation through the heme oxygenase (HO) system, exerts cytoprotective effects by reducing the expression of proinflammatory mediators, preventing vascular constriction, decreasing platelet aggregation, and inhibiting apoptosis (41, 66).…”

mentioning

confidence: 99%

5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury

Hou

Cai

Kitajima

et al. 2013

American Journal of Physiology-Renal Physiology

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(Fe 2ϩ ), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe 2ϩ 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe 2ϩ increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe 2ϩ treatments significantly decreased the tubular damage and number of apoptotic cells. IRIinduced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe 2ϩ group. Furthermore, mRNA expression of HO-1, TNF-␣, and interferon-␥ was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-␣ and interferon-␥ were decreased in the 5-ALA/Fe 2ϩ -pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/ Fe 2ϩ can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.5-aminolevulinic acid; carbon monoxide; hemeoxygenase-1; kidney; ischemia-reperfusion injury; oxidative stress RENAL ISCHEMIA-REPERFUSION INJURY (IRI) is a complex pathophysiological process involving programmed cell death (PCD) and oxidant damage that leads to acute renal failure (AFR). The mortality rate of ARF remains between 50% and 70% among patients who receive intensive care who require dialysis and ranges between 25% and 100% in postoperative patients suffering from ARF. Renal IRI is unavoidable in renal transplantation and may lead to acute posttransplant tubular necrosis (21,24,49,55) and delayed graft function (27,47). Recent findings have indicated that carbon monoxide (CO), an endogenous byproduct of heme degradation through the heme oxygenase (HO) system, exerts cytoprotective effects by reducing the expression of proinflammatory mediators, preventing vascular constriction, decreasing platelet aggregation, and inhibiting apoptosis (41, 66). Subsequent studies have actively used exogenous CO to treat various experimental disease conditions. In the field of transplantation, CO has been shown to inhibit acute and chronic allograft rejection (37, 57) and the rejection of xenografts (53). Furthermore, studies in the area of renal disease have reported that CO-releasing molecules (CORMs) protect against the renal damage in ischemia-induced ARF in mice (63), cisplatin-induced nephrotoxicity in rats (60), and cold ischemia and reperfusion injury during kidney transplantation of both iso-and allografts in rats (5) and mice (55).5-Aminolevulinic acid (5-ALA), an intermediate in heme synthesis, is fundamental for aerobic energy metabolism. It is used as a photo sensitizer precursor for photodynamic diagnosis and photodynamic therapy to identify and kill tu...

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“…Blood samples were analyzed for creatinine, while urinary samples were analyzed for creatinine, protein and N -acetyl-β- d -glucosaminidase (NAGase) activity as described previously [ 13 ]. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) were determined using a commercially available enzyme-linked immunosorbent assay kit (BioPorto Diagnostics A/S, Gentofte, Denmark) [ 22 ]. NGAL and NAGase are both markers of tubular injury.…”

Section: Methodsmentioning

confidence: 99%

Adenosine, lidocaine and Mg2+improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

et al. 2014

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IntroductionThe combination of Adenosine (A), lidocaine (L) and Mg2+ (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model.MethodsPigs (37 to 42 kg) were randomized into: 1) Control (n = 8) or 2) ALM (n = 8) followed by lipopolysaccharide infusion (1 μg∙kg-1∙h-1) for five hours. ALM treatment consisted of 1) a high dose bolus (A (0.82 mg/kg), L (1.76 mg/kg), M (0.92 mg/kg)), 2) one hour continuous infusion (A (300 μg∙kg-1 ∙min-1), L (600 μg∙kg-1 ∙min-1), M (336 μg∙kg-1 ∙min-1)) and three hours at a lower dose (A (240∙kg-1∙min-1), L (480 μg∙kg-1∙min-1), M (268 μg∙kg-1 ∙min-1)); controls received normal saline. Hemodynamic, cardiac, pulmonary, metabolic and renal functions were evaluated.ResultsALM lowered mean arterial pressure (Mean value during infusion period: ALM: 47 (95% confidence interval (CI): 44 to 50) mmHg versus control: 79 (95% CI: 75 to 85) mmHg, P <0.0001). After cessation of ALM, mean arterial pressure immediately increased (end of study: ALM: 88 (95% CI: 81 to 96) mmHg versus control: 86 (95% CI: 79 to 94) mmHg, P = 0.72). Whole body oxygen consumption was significantly reduced during ALM infusion (ALM: 205 (95% CI: 192 to 217) ml oxygen/min versus control: 231 (95% CI: 219 to 243) ml oxygen/min, P = 0.016). ALM treatment reduced pulmonary injury evaluated by PaO2/FiO2 ratio (ALM: 388 (95% CI: 349 to 427) versus control: 260 (95% CI: 221 to 299), P = 0.0005). ALM infusion led to an increase in heart rate while preserving preload recruitable stroke work. Creatinine clearance was significantly lower during ALM infusion but reversed after cessation of infusion. ALM reduced tumor necrosis factor-α peak levels (ALM 7121 (95% CI: 5069 to 10004) pg/ml versus control 11596 (95% CI: 9083 to 14805) pg/ml, P = 0.02).ConclusionALM infusion induces a reversible hypotensive and hypometabolic state, attenuates tumor necrosis factor-α levels and improves cardiac and pulmonary function, and led to a transient drop in renal function that was reversed after the treatment was stopped.

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Fast Detection of Renal Ischemia in Transplanted Kidneys With Delayed Graft Function—An Experimental Study

Abstract: Microdialysis provided an early warning of arterial occlusion in transplanted grafts with delayed graft function. It may become a valuable tool for postoperative monitoring and detection of thrombosis after renal transplantation.

Cited by 12 publications

References 23 publications

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury

Adenosine, lidocaine and Mg2+improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

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