Renal hemosiderosis secondary to intravascular hemolysis after mitral valve repair

Lee, In Hee; Kang, Gun Woo; Kim, Chang-Yeon; Lee, Sunjae; Kim, Minkyung; Ahn, Dong Jik

doi:10.1097/md.0000000000018798

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…Our findings suggest that these substrates are internalized into the cell together with α 2 M, where they undergo lysosomal degradation. Intravascular hemolysis causes autoimmune diseases 38 , infection 39 , and mechanical stress 40 (e.g., running 41 ), which might be associated with accumulation of normally intracellular proteins. Because more than half of all cells in the human body are erythrocytes, sufficient hemolysis would expose numerous intracellular proteins to the extracellular environment.…”

Section: Discussionmentioning

confidence: 99%

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Tomihari

Kiyota

Matsuura

et al. 2023

Sci Rep

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Proteostasis regulates protein folding and degradation; its maintenance is essential for resistance to stress and aging. The loss of proteostasis is associated with many age-related diseases. Within the cell, molecular chaperones facilitate the refolding of misfolded proteins into their bioactive forms, thus preventing undesirable interactions and aggregation. Although the mechanisms of intracellular protein degradation pathways for intracellular misfolded proteins have been extensively studied, the protein degradation pathway for extracellular proteins remain poorly understood. In this study, we identified several misfolded proteins that are substrates for alpha 2-macroglobulin (α2M), an extracellular chaperone. We also established a lysosomal internalization assay for α2M, which revealed that α2M mediates the lysosomal degradation of extracellular misfolded proteins. Comparative analyses of α2M and clusterin, another extracellular chaperone, indicated that α2M preferentially targets aggregation-prone proteins. Thus, we present the degradation pathway of α2M, which interacts with aggregation-prone proteins for lysosomal degradation via selective internalization.

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Section: Discussionmentioning

confidence: 99%

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Tomihari

Kiyota

Matsuura

et al. 2023

Sci Rep

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“…Interestingly, IFTA was decreased in transgenic mice with dilated cardiomyopathy that were treated with NAC as compared to wild‐type mice (Giam et al, 2017 ), suggesting that this treatment is effective not only in experimental models of direct kidney injury but also in other diseases associated with extrarenal etiologies of CKD. Several case reports show improving kidney function after treatment with NAC in patients with biopsy‐proven hemosiderosis in the kidney (Ackermann et al, 2004 ; Lee et al, 2020 ). In CKD patients, especially in those on chronic dialysis, the beneficial effects of treatments with different antioxidants on serum C‐reactive protein levels (a biomarker of kidney dysfunction) have been reported (Supriyadi et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

N‐acetylcysteine ameliorates hematuria‐associated tubulointerstitial injury in 5/6 nephrectomy mice

Medipally

Xiao

Satoskar

et al. 2023

Physiological Reports

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Chronic kidney disease (CKD) is characterized by increased interstitial fibrosis and tubular atrophy (IFTA) in the kidney. Chronic hematuria is a hallmark of several human kidney diseases and often is seen in patients on anticoagulation therapy. We had previously demonstrated that chronic hematuria associated with warfarin increases IFTA in 5/6 nephrectomy (5/6NE) rats, and such treatment increases reactive oxygen species (ROS) in the kidney. The goal of this study was to evaluate the effects of the antioxidant N‐acetylcysteine (NAC) on the progression of IFTA in 5/6NE mice. 5/6NE C57BL/6 and 5/6NE 129S1/SvImJ mice were treated with warfarin alone or with warfarin and NAC for 23 weeks. Serum creatinine (SCr), hematuria, blood pressure (BP), and ROSs in the kidney were measured; kidney morphology was evaluated. Warfarin doses were titrated to achieve prothrombin time (PT) increase to the levels seen with therapeutic human doses. Warfarin treatment resulted in an increased SCr, systolic BP, hematuria, expression of TGF‐ß and ROS in the kidney in both mouse strains. Tumor necrosis factor alpha (TNF‐ɑ) levels in the serum were increased in 5/6NE mice treated with warfarin. IFTA was increased as compared with control 5/6NE mice, and this increase in IFTA was more prominent in 129S1/SvImJ than in C57BL/6 mice. NAC ameliorated the warfarin‐associated increase in SCr and BP but not hematuria. IFTA, TGF‐ß, and ROS in the kidney as well as TNF‐ɑ levels in the serum were reduced in mice treated with NAC and warfarin as compared to mice treated with warfarin alone. NAC mitigates the increase in SCr and IFTA in mice with chronic hematuria by reducing oxidative stress in the kidney. This data open novel possibilities for treatments in CKD patients.

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“…The high shear force can be caused by the annular leakage of the artificial valve, the impact of blood flow on the rough surface of the artificial material, the turbulence formed by the reflux beam, and the special reflux beam types (impact, acceleration, split type). When the shear force increases beyond the maximum stress that the erythrocyte membrane can bear, it will lead to cell breakage [Ishida 2015;Lee 2020;Ishibashi 2005;Qian 2010;Chan 2014]. Some researchers have conducted in vitro experiments and found that when the shear force reaches 50-450 PA, it can lead to red blood cell destruction, and when the flow rate cross valve is 5 m/s, the shear force of blood flow on the aortic wall can be as high as 870 PA.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and Treatment of Mechanical Hemolysis after Mitral Repair in Adult

Wen

et al. 2021

HSF

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Background: Mitral repair has been widely used in the treatment of secondary mitral lesions in recent years. Hemolytic anemia is known to be a rare complication after mitral repair. This study aimed to investigate the diagnosis and treatment of mechanical hemolysis after mitral repair in adults. Methods: In this retrospective study, we reviewed the medical records of patients undergoing mitral repair complicated with mechanical hemolysis at our institution between August 2006 and May 2020. Results: Twenty-four patients undergoing mitral repair complicated with mechanical hemolysis were included in the study. They were divided into two groups: the reoperation group (patients who underwent reoperation; N = 18) and the conservative treatment group (patients who received symptomatic treatments, including blood transfusion, diuresis, alkalization of urine, liver protection, hemodialysis, and oral metoprolol; N = 6. All patients in the reoperation group underwent mitral valve replacement. There were six hospital deaths, all in the conservative treatment group. Seventeen of eighteen patients (94.4%) completed follow up. Fifteen of seventeen survivors (88.2%) were in NYHA class I and 11.8% (2/17) in NYHA class II at the last time follow up. Conclusions: Hemolysis is a sign of failure of mitral repair. Reoperation is the best choice once the hemolysis has been diagnosed. Reoperation should be carried out as soon as possible.

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Renal hemosiderosis secondary to intravascular hemolysis after mitral valve repair

Cited by 6 publications

References 19 publications

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins

N‐acetylcysteine ameliorates hematuria‐associated tubulointerstitial injury in 5/6 nephrectomy mice

Diagnosis and Treatment of Mechanical Hemolysis after Mitral Repair in Adult

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