Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1^M-KO), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1^M-KO exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1^M-KO mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b⁺ F4/80^lo subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1⁺ CD11b⁺ F4/80^lo myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1^M-KO mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.

Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). IRI-induced AKI releases proinflammatory cytokines (e.g. IL-1β, TNF-α, IL-6) that induce a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage. AKI is associated with poor outcomes, particularly when extrarenal complications or distant organ injuries occur. Acute lung injury (ALI) is a major remote organ dysfunction associated with AKI. Hence, kidney-lung cross talk remains a clinical challenge, especially in critically ill population. The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against renal IRI and may be preventively induced using hemin prior to renal insult. However, the use of hemin-induced HO-1 to prevent AKI-induced ALI remains poorly investigated. Mice received an intraperitoneal injection of hemin or sterile saline 1 day prior to surgery. Twenty-four hours later, mice underwent bilateral renal IRI for 26 minutes or sham surgery. After 4 or 24 hours of reperfusion, mice were sacrificed. Hemin-induced HO-1 improved renal outcomes after IRI (i.e. fewer renal damage, renal inflammation and oxidative stress). This protective effect was associated with a dampened systemic inflammation (ie IL-6 and KC). Subsequently, a mitigated lung inflammation was found in hemin-treated mice (ie neutrophils influx and lung KC). The present study demonstrates that hemin-induced HO-1 controls the magnitude of renal IRI and the subsequent AKI-induced ALI. Therefore, targeting HO-1 represents a promising approach to prevent the impact of renal IRI on distant organs, such as lung.

Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). Renal IRI combines major events, including a strong inflammatory immune response leading to extensive cell injuries, necrosis and late interstitial fibrosis. Macrophages act as key players in IRI-induced AKI by polarizing into proinflammatory M1 and anti-inflammatory M2 phenotypes. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1), mediates protection against renal IRI and modulates macrophage polarization by enhancing a M2 subset. Hereafter, we review the dual effect of macrophages in the pathogenesis of IRI-induced AKI and discuss the critical role of HO-1 expressing macrophages.

Varicocele is one of the causes of male infertility. Treatment aims to improve the chance of conception despite lasting controversies about benefits of varicocele repair on fertility. Many techniques have been described for varicocele management including the antegrade scrotal sclerotherapy (ASS). Interestingly, ASS is often presented as a safe, easy, and cost-effective procedure with low recurrence and complication rates. However, we report the first case of spinal cord paralysis following ASS probably due to embolization of venous anastomoses between left spermatic and ascending lumbar veins, which were undetected at preoperative phlebography. Based on this case and recent literature, we raise questions about the safety of ASS and try to figure out what would be the best way to improve the detectability of potential harmful anastomoses at preoperative phlebography.