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Introduction: Acute kidney injury (AKI) and myocardial injury (MI) are severe conditions in patients with severe burn injury, and combination of both is even worst and is called the cardiorenal syndrome (CRS). Identifying a distinct cardiorenal phenotype could significantly enhance the management of these patients. Galectin-3 (Gal3) and soluble CD146 (sCD146) are biomarkers for renal and cardiac injuries. This study aims to assess the occurrence and reliability of these biomarkers in recognizing CRS in individuals who have been severely burn., Methods: This study is a single-center prospective proof-of-concept study involving patients with severe burn injuries. Plasma samples for Gal3 and sCD146 measurements were collected daily during the initial 7 days following admission. CRS was defined after 24 h of admission by the association of AKI stage 1 or more (KDIGO definition) and MI defined on high sensitive troponin (hsTnT) (variation >20% baseline value or absolute value >40 ng/mL)., Results: Forty patients met the inclusion criteria and were included in this study. Thirty-eight patients had CRS. The pooled values of Gal3 or combination of Gal3 and sCD146 values following 7 days after admission were associated with CRS with an odds ratio (OR) of 1.145 (95% CI: 1.081-1.211), p < 0.001, and 1.147 (95% CI: 1.085-1.212), p < 0.001, respectively. Gal3 values at admission (D0) had a predictive performance for CRS with an AUC of 0.78 (95% CI: 0.63-0.93), and this performance improved when using the combination of Gal3 and sCD146 values at admission (D0), with an AUC of 0.81 (95% CI: 0.66-0.96). Gal3 levels during the first 7 days were associated with patients experiencing AKI and no MI, with an OR of 1.129 (95% CI: 1.065-1.195), p < 0.001, and MI without AKI with an OR of 1.095 (95% CI: 1.037-1.167), p < 0.001. sCD146 alone was not associated with AKI without MI or MI without AKI and was poorly associated with CRS., Conclusion: In severely burned patients, CRS is a frequent and severe condition. Gal3 values during the first 7 days following admission were associated with CRS. The use of sCD146 with Gal3 improved prediction performance for CRS identification. The use of such biomarkers to identify CRS is important and needs to be confirmed in other studies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

To guide the development of therapeutic interventions for acute kidney injury, elucidating the deleterious pathways of this global health problem is highly warranted. Emerging evidence has indicated a pivotal role of endothelial dysfunction in the etiology of this disease. We found that the class III semaphorin SEMA3C was ectopically upregulated with full length protein excreted into the blood and truncated protein secreted into the urine upon kidney injury and hypothesized a role for SEAM3C in acute kidney injury. Sema3c was genetically abrogated during acute kidney injury and subsequent kidney morphological and functional defects in two well-characterized models of acute kidney injury; warm ischemia/reperfusion and folic acid injection were analyzed. Employing a beta actin-dependent, inducible knockout of Sema3c, we demonstrate that in acute kidney injury SEMA3C promotes interstitial edema, leucocyte infiltration and tubular injury. Additionally, intravital microscopy combined with Evans Blue dye extravasation and primary culture of magnetically sorted peritubular endothelial cells identified a novel role for SEMA3C in promoting vascular permeability. Thus, our study points to microvascular permeability as an important driver of injury in acute kidney injury, and to SEMA3C as a novel permeability factor and potential target for therapeutic intervention., (Copyright © 2022 International Society of Nephrology. All rights reserved.)

Background: Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages., Methods: This is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition., Results: Two thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI 95% [0.74-0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI 95% [1.68-1.93], p < 0.001, non-adjusted and OR 1.37 CI 95% [1.27-1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screat adm , pNGAL with a NRI of 0.27 CI 95% (0.16-0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively)., Conclusion: Plasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission. Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011., (© 2022. The Author(s).)

Background: The matricellular protein periostin has been associated with CKD progression in animal models and human biopsy specimens. Periostin functions by interacting with extracellular matrix components to drive collagen fibrillogenesis and remodeling or by signaling through cell-surface integrin receptors to promote cell adhesion, migration, and proliferation. However, its role in AKI is unknown., Methods: We used mice with conditional tubule-specific overexpression of periostin or knockout mice lacking periostin expression in the renal ischemia-reperfusion injury model, and primary cultures of isolated tubular cells in a hypoxia-reoxygenation model., Results: Tubular epithelial cells showed strong production of periostin during the repair phase of ischemia reperfusion. Periostin overexpression protected mice from renal injury compared with controls, whereas knockout mice showed increased tubular injury and deteriorated renal function. Periostin interacted with its receptor, integrin- β 1, to inhibit tubular cell cycle arrest and apoptosis in in vivo and in vitro models. After ischemia-reperfusion injury, periostin-overexpressing mice exhibited diminished expression of proinflammatory molecules and had more F4/80 + macrophages compared with knockout mice. Macrophages from periostin-overexpressing mice showed increased proliferation and expression of proregenerative factors after ischemia-reperfusion injury, whereas knockout mice exhibited the opposite. Coculturing a macrophage cell line with hypoxia-treated primary tubules overexpressing periostin, or treating such macrophages with recombinant periostin, directly induced macrophage proliferation and expression of proregenerative molecules., Conclusions: In contrast to the detrimental role of periostin in CKD, we discovered a protective role of periostin in AKI. Our findings suggest periostin may be a novel and important mediator of mechanisms controlling renal repair after AKI., (Copyright © 2020 by the American Society of Nephrology.)

Acute kidney injury is a major risk factor for subsequent chronic renal and/or cardiovascular complications. Previous studies have shown that Notch3 was de novo expressed in the injured renal epithelium in the early phases of chronic kidney disease. Here we examined whether Notch3 is involved in the inflammatory response and the epithelial cell damage that typifies ischemic kidneys using Notch3 knockout mice and mice with short-term activated Notch3 signaling (N3ICD) in renal epithelial cells. After ischemia/reperfusion, N3ICD mice showed exacerbated infiltration of inflammatory cells and severe tubular damage compared to control mice. Inversely, Notch3 knockout mice were protected against ischemia/reperfusion injury. Renal macrophages derived from Notch3 knockout mice failed to activate proinflammatory cytokines. Chromatin immunoprecipitation analysis of the Notch3 promoter identified NF-κB as the principal inducer of Notch3 in ischemia/reperfusion. Thus, Notch3 induced by NF-κB in the injured epithelium sustains a proinflammatory environment attracting activated macrophages to the site of injury leading to a rapid deterioration of renal function and structure. Hence, targeting Notch3 may provide a novel therapeutic strategy against ischemia/reperfusion and acute kidney injury by preservation of epithelial structure and disruption of proinflammatory signaling., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)