記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease characterized by necrotizing inflammation of small blood vessels. Glucocorticoids (GC) in combination with rituximab or cyclophosphamide can reduce AAV-related mortality and rescue renal function. However, several side effects associated with these agents, including GC toxicity, are concerning. Avacopan, an inhibitor of the C5a receptor, is now available for AAV treatment and is expected to mitigate GC toxicity. We present a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis (MPA) with rapidly progressive glomerulonephritis treated with an early switch from GC to avacopan in combination with rituximab during induction therapy. Over a 6-month treatment period, clinical remission was achieved and maintained without infection or elevated liver enzyme levels. Efficacy and safety data regarding avacopan for AAV induction therapy remain limited. Therefore, more case reports are required to clarify the role of avacopan in AAV induction and maintenance therapy. Since the MPO-ANCA titer remained elevated despite the clinical remission of AAV in this case, the ANCA titer may not necessarily be a reliable biomarker for predicting AAV relapse when avacopan is applied as an induction therapy for AAV.

DOI： 10.1007/s13730-023-00841-3

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia-reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) and Vash2 homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration.

DOI： 10.3390/ijms21124545

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/-) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/- mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/- mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

DOI： 10.1152/ajprenal.00045.2019

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin. Male C57BL/6 J wild-type and ERRα-/- mice received a single intraperitoneal injection of 20 mg/kg cisplatin. Seventy-two hours after the injection, kidney function and morphology were evaluated. ERRα expression was observed in renal tubules, and cisplatin inhibited its translocation into nuclei. ERRα deficiency exacerbated cisplatin-induced renal dysfunction and tubular injury, as well as oxidative stress and apoptosis. ERRα-/- mice kidneys revealed lower mitochondrial DNA content and swollen mitochondria with reduced cristae. In addition, these mice had lower expression of the mitochondrial fusion protein mitofusin-2. The cisplatin-induced decrease in mitochondrial DNA and altered mitochondrial structure were more severe in ERRα-/- mice. In cultured mouse proximal tubular epithelial cells, the ERRα inverse agonist XCT-790 significantly inhibited mitofusin-2 expression and induced mitochondrial fragmentation. Taken together, our findings suggest the involvement of ERRα in the progression of cisplatin-induced AKI probably through impaired mitochondrial dynamics.

DOI： 10.1016/j.bbrc.2018.03.080

PubMed

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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