Macrophage involvement in the kidney repair phase after ischaemia/reperfusion injury

Vinuesa, Eugenia; Hotter, Georgina; Jung, Michaela; Herrero‐Fresneda, Immaculada; Torrás, Joan; Solà, Anna

doi:10.1002/path.2259

Cited by 120 publications

(105 citation statements)

References 21 publications

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“…A study preceding that of Jung et al from the same group demonstrated that renal regeneration, prompted by mediators including IL-10, occurs only following, and not during, ischemia/reperfusion injury. 46 This segregation of the two inflammatory arms, with respect to the inflammatory milieu, is consistent with our understanding of the transition in macrophages, which secretes both IL-6 and IL-10, from a state that promotes injury to one that initiates repair. 47 Our study also expands on the literature of these cytokines in the perioperative setting, which has generally been conducted with small cohorts, in single-center settings, and with lack of defined hard outcomes.…”

Section: J Am Soc Nephrol 26: 3123-3132 2015supporting

confidence: 80%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

176

119

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Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a $50% or $0.3-mg/dl increase in serum creatinine from baseline. Pre-and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. AKI is a common complication of cardiac surgery, leading to increased morbidity and mortality. 1 Current paradigms of diagnosis and treatment are based on serum creatinine and are thus insensitive. These limitations have spurred the search for novel proteins that are involved in the process of kidney injury. 2,3 While AKI is traditionally recognized and diagnosed by renal functional impairment and structural damage, it is also an inflammatory condition. Understanding and measuring the processes of inflammation in AKI may provide unique tools for its assessment and prediction.To this end, we developed an ancillary study to our large, multicenter cohort study of adult patients

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Section: J Am Soc Nephrol 26: 3123-3132 2015supporting

confidence: 80%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

176

119

View full text Add to dashboard Cite

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“…In many settings regeneration of the kidney is macrophage dependent, evidenced by the switch of macrophage phenotype from a pro-inflammatory to an anti-inflammatory phenotype, 21 which is followed by the production of angiogenic and anti-inflammatory factors in addition to phagocytic tissue remodeling. 22,61 The precise phenotype of the macrophages seen in the repairing kidney in our study does not strictly conform to the M1/M2 dichotomy, because we see expression of genes associated with both extremes and the profile changes with time. Mosser and Edwards 48 have suggested a third macrophage classification, associated with wound healing, that is distinct from the M2 category.…”

Section: Discussionmentioning

confidence: 67%

Colony-Stimulating Factor-1 Promotes Kidney Growth and Repair via Alteration of Macrophage Responses

Alikhan

Jones

Williams

et al. 2011

The American Journal of Pathology

132

134

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Colony-stimulating factor (CSF)-1 controls the survival, proliferation, and differentiation of macrophages, which are recognized as scavengers and agents of the innate and the acquired immune systems. Because of their plasticity, macrophages are endowed with many other essential roles during development and tissue homeostasis. We present evidence that CSF-1 plays an important trophic role in postnatal organ growth and kidney repair. Notably, the injection of CSF-1 postnatally enhanced kidney weight and volume and was associated with increased numbers of tissue macrophages. Moreover, CSF-1 promotes postnatal renal repair in mice after ischemia-reperfusion injury by recruiting and influencing macrophages toward a reparative state. CSF-1 treatment rapidly accelerated renal repair with tubular epithelial cell replacement, attenuation of interstitial fibrosis, and functional recovery. Analysis of macrophages from CSF-1-treated kidneys showed increased expression of insulin-like growth factor-1 and anti-inflammatory genes that are known CSF-1 targets. Taken together, these data suggest that CSF-1 is important in kidney growth and the promotion of endogenous repair and resolution of inflammatory injury.

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“…Recent studies in other forms of immune-mediated renal injury raise the possibility that it is the effector phenotype of the recruited macrophages rather than their presence alone that determines the extent of renal parenchymal injury. 13,14 Macrophages exhibit a range of phenotypes, a phenomenon that has been described as macrophage polarization or heterogeneity. [15][16][17] The "classically" activated or F4/80 ϩ…”

mentioning

confidence: 99%

Distinct Macrophage Phenotypes Contribute to Kidney Injury and Repair

Lee¹,

Huen²,

Nishio³

et al. 2011

Journal of the American Society of Nephrology

756

796

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The ischemically injured kidney undergoes tubular cell necrosis and apoptosis, accompanied by an interstitial inflammatory cell infiltrate. In this study, we show that iNos-positive proinflammatory (M1) macrophages are recruited into the kidney in the first 48 hours after ischemia/reperfusion injury, whereas arginase 1-and mannose receptor-positive, noninflammatory (M2) macrophages predominate at later time points. Furthermore, depletion of macrophages before ischemia/reperfusion diminishes kidney injury, whereas depletion at 3 to 5 days after injury slows tubular cell proliferation and repair. Infusion of Ifn␥-stimulated, bone marrowderived macrophages into macrophage-depleted mice at the time of kidney reperfusion restored injury to the level seen without macrophage depletion, suggesting that proinflammatory macrophages worsen kidney damage. In contrast, the appearance of macrophages with the M2 phenotype correlated with the proliferative phase of kidney repair. In vitro studies showed that IFN␥-stimulated, proinflammatory macrophages begin to express markers of M2 macrophages when cocultured with renal tubular cells. Moreover, IL-4 -stimulated macrophages with an M2 phenotype, but not IFN␥-stimulated proinflammatory macrophages, promoted renal tubular cell proliferation. Finally, tracking fluorescently labeled, IFN␥-stimulated macrophages that were injected after injury showed that inflammatory macrophages can switch to an M2 phenotype in the kidney at the onset of kidney repair. Taken together, these studies show that macrophages undergo a switch from a proinflammatory to a trophic phenotype that supports the transition from tubule injury to tubule repair.

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Macrophage involvement in the kidney repair phase after ischaemia/reperfusion injury

Cited by 120 publications

References 21 publications

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Colony-Stimulating Factor-1 Promotes Kidney Growth and Repair via Alteration of Macrophage Responses

Distinct Macrophage Phenotypes Contribute to Kidney Injury and Repair

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