Severe hypoxemia after radiofrequency ablation for atrial fibrillation in palliatively repaired tetralogy of Fallot: A case report.

Background: Patients with tetralogy of Fallot (TOF) often have arrhythmias, commonly being atrial fibrillation (AF). Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia, but the risk of complications may increase in patients with conditions such as TOF.

Case Summary: We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt.

AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model.

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice.

The Role of Parietal Epithelial Cells in the Pathogenesis of Podocytopathy.

Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions.

Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis.

Background: Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified.

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury.

Background: Macroautophagy (autophagy) is a cellular recycling process involving the destruction of damaged organelles and proteins in intracellular lysosomes for efficient nutrient reuse.

Summary: Impairment of the autophagy-lysosome pathway is tightly associated with multiple kidney diseases, such as diabetic nephropathy, proteinuric kidney disease, acute kidney injury, crystalline nephropathy, and drug- and heavy metal-induced renal injury. The impairment in the process of autophagic clearance may induce injury in renal intrinsic cells by activating the inflammasome, inducing cell cycle arrest, and cell death.

Cyclosporine A blocks autophagic flux in tubular epithelial cells by impairing TFEB-mediated lysosomal function.

Cyclosporine A (CsA) is an immunosuppressor widely used for the prevention of acute rejection during solid organ transplantation. However, severe nephrotoxicity has substantially limited its long-term usage. Recently, an impaired autophagy pathway was suggested to be involved in the pathogenesis of chronic CsA nephrotoxicity.

SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy.

Macroautophagy/autophagy dysregulation has been noted in diabetic nephropathy; however, the regulatory mechanisms controlling this process remain unclear. In this study, we showed that SMAD3 (SMAD family member 3), the key effector of TGFB (transforming growth factor beta)-SMAD signaling, induces lysosome depletion via the inhibition of TFEB-dependent lysosome biogenesis. The pharmacological inhibition or genetic deletion of SMAD3 restored lysosome biogenesis activity by alleviating the suppression of , thereby protecting lysosomes from depletion and improving autophagic flux in renal tubular epithelial cells in diabetic nephropathy.

Autophagy Inhibition Sensitizes Renal Tubular Epithelial Cell to G1 Arrest Induced by Transforming Growth Factor beta (TGF-β).

BACKGROUND Cell cycle arrest and autophagy have been demonstrated to be involved in various transforming growth factor (TGF)-ß-mediated phenotype alterations of tubular epithelial cells (TECs) and tubulointerstitial fibrosis. But the relationship between cell cycle arrest and the autophagy induced by TGF-ß has not been explored well. MATERIAL AND METHODS The effects of autophagy inhibition on TGF-ß-induced cell cycle arrest in TECs were explored in vitro.

Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis.

BACKGROUND The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its association with glomerular lesions were investigated in a mouse model of LN. MATERIAL AND METHODS Eighteen MRL/lpr mice with severe proteinuria were randomly divided into 2 equal groups and intraperitoneally injected with dexamethasone (DEX) or saline; 4 age-matched mice with mild proteinuria served as controls. Serum creatinine and urinary protein levels were analyzed, and kidney histological changes were observed by periodic acid-Schiff and Sirius Red staining.

Blockage of the lysosome-dependent autophagic pathway contributes to complement membrane attack complex-induced podocyte injury in idiopathic membranous nephropathy.

Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model.