Maoqing Tian, Lu Zhang, Yujuan Wang, Meili Deng, Cancan Peng, W. Liang, G. Ding, Bo Shen, Huiming Wang
Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.
{"title":"Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis","authors":"Maoqing Tian, Lu Zhang, Yujuan Wang, Meili Deng, Cancan Peng, W. Liang, G. Ding, Bo Shen, Huiming Wang","doi":"10.1159/000521564","DOIUrl":"https://doi.org/10.1159/000521564","url":null,"abstract":"Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"40 1","pages":"168 - 179"},"PeriodicalIF":3.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90564396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. Summary: ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. Key Message: Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.
{"title":"Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease","authors":"Henry H. L. Wu, R. Chinnadurai","doi":"10.1159/000521162","DOIUrl":"https://doi.org/10.1159/000521162","url":null,"abstract":"Background: Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. Summary: ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. Key Message: Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"1 1","pages":"103 - 114"},"PeriodicalIF":3.7,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78244529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Wang, Zhuoshu Li, Longfei Mao, Mingyi Zhao, Bingchang Yang, Xi Tao, Yuxiang Li, Guangming Yin
Background: Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. Summary: Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO−), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O2−) and hydrogen peroxide (H2O2). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H2 in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. Key Messages: This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.
{"title":"Hydrogen: A Novel Treatment Strategy in Kidney Disease","authors":"Bo Wang, Zhuoshu Li, Longfei Mao, Mingyi Zhao, Bingchang Yang, Xi Tao, Yuxiang Li, Guangming Yin","doi":"10.1159/000520981","DOIUrl":"https://doi.org/10.1159/000520981","url":null,"abstract":"Background: Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. Summary: Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO−), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O2−) and hydrogen peroxide (H2O2). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H2 in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. Key Messages: This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"155 1","pages":"126 - 136"},"PeriodicalIF":3.7,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73446110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gestation complications have a recurrence risk and could predispose to each other in the next pregnancy. We aimed to evaluate the relationship between a history of adverse pregnancy and maternal-fetal outcomes in subsequent pregnancy in patients with Immunoglobulin A nephropathy (IgAN). Methods: A retrospective cohort study from a Chinese single center was conducted. Pregnant women with biopsy-proven primary IgAN and aged ≥18 years were enrolled and divided into the 2 groups by a history of adverse pregnancy. The primary outcome was adverse pregnancy outcome, which included maternal-fetal outcomes. Logistical regression model was used to evaluate the association of a history of adverse pregnancy with subsequent adverse maternal and fetal outcomes. Results: Ninety-one women with 100 pregnancies were included, of which 54 (54%) pregnancies had a history of adverse pregnancy. IgAN patients with adverse pregnancy history had more composite maternal outcomes (70.4% vs. 45.7%, p = 0.012), while there was no difference in the composite adverse fetal outcomes between the 2 groups (55.6% vs. 45.7%). IgAN patients with a history of adverse pregnancy were associated with an increased risk of subsequent adverse maternal outcomes (adjusted odds ratio [OR], 2.64; 95% CI, 1.07–6.47). Similar results were shown in those with baseline serum albumin <3.5 g/dL, 24 h proteinuria ≥1 g/day, and a history of hypertension. There was no association between a history of adverse pregnancy and subsequent adverse fetal outcomes in IgAN patients (adjusted OR, 1.56; 95% CI, 0.63–3.87). Conclusion: A history of adverse pregnancy was associated with an increased risk of subsequent adverse maternal outcomes, but not for adverse fetal outcomes in IgAN patients.
背景:妊娠期并发症有复发的危险，且在下次妊娠时有相互易感性。我们的目的是评估不良妊娠史与免疫球蛋白a肾病(IgAN)患者随后妊娠的母胎结局之间的关系。方法:采用中国单中心回顾性队列研究。入选活检证实为原发性IgAN且年龄≥18岁的孕妇，根据不良妊娠史分为两组。主要结局为不良妊娠结局，包括母胎结局。logistic回归模型用于评估不良妊娠史与随后不良母婴结局的关系。结果:纳入91例100次妊娠，其中54例(54%)有不良妊娠史。有不良妊娠史的IgAN患者产妇综合结局较多(70.4% vs. 45.7%， p = 0.012)，而两组胎儿综合不良结局无差异(55.6% vs. 45.7%)。有不良妊娠史的IgAN患者与随后不良产妇结局的风险增加相关(校正优势比[OR]， 2.64;95% ci, 1.07-6.47)。基线血清白蛋白<3.5 g/dL、24小时蛋白尿≥1 g/天、有高血压史的患者也出现了类似的结果。IgAN患者不良妊娠史与随后的不良胎儿结局之间没有关联(校正OR, 1.56;95% ci, 0.63-3.87)。结论:不良妊娠史与随后不良产妇结局的风险增加有关，但与IgAN患者不良胎儿结局的风险无关。
{"title":"History of Adverse Pregnancy on Subsequent Maternal-Fetal Outcomes in Patients with Immunoglobulin A Nephropathy: A Retrospective Cohort Study from a Chinese Single Center","authors":"Xingji Lian, L. Fan, Xin Ning, Cong Wang, Yi-fen Lin, Wenfang Chen, Wei Chen, Xueqing Yu","doi":"10.1159/000520586","DOIUrl":"https://doi.org/10.1159/000520586","url":null,"abstract":"Background: Gestation complications have a recurrence risk and could predispose to each other in the next pregnancy. We aimed to evaluate the relationship between a history of adverse pregnancy and maternal-fetal outcomes in subsequent pregnancy in patients with Immunoglobulin A nephropathy (IgAN). Methods: A retrospective cohort study from a Chinese single center was conducted. Pregnant women with biopsy-proven primary IgAN and aged ≥18 years were enrolled and divided into the 2 groups by a history of adverse pregnancy. The primary outcome was adverse pregnancy outcome, which included maternal-fetal outcomes. Logistical regression model was used to evaluate the association of a history of adverse pregnancy with subsequent adverse maternal and fetal outcomes. Results: Ninety-one women with 100 pregnancies were included, of which 54 (54%) pregnancies had a history of adverse pregnancy. IgAN patients with adverse pregnancy history had more composite maternal outcomes (70.4% vs. 45.7%, p = 0.012), while there was no difference in the composite adverse fetal outcomes between the 2 groups (55.6% vs. 45.7%). IgAN patients with a history of adverse pregnancy were associated with an increased risk of subsequent adverse maternal outcomes (adjusted odds ratio [OR], 2.64; 95% CI, 1.07–6.47). Similar results were shown in those with baseline serum albumin <3.5 g/dL, 24 h proteinuria ≥1 g/day, and a history of hypertension. There was no association between a history of adverse pregnancy and subsequent adverse fetal outcomes in IgAN patients (adjusted OR, 1.56; 95% CI, 0.63–3.87). Conclusion: A history of adverse pregnancy was associated with an increased risk of subsequent adverse maternal outcomes, but not for adverse fetal outcomes in IgAN patients.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"26 1","pages":"160 - 167"},"PeriodicalIF":3.7,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79359050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haiyang Li, Jiachuan Xiong, Yupei Du, Yinghui Huang, Jinghong Zhao
Background: Dual-specificity phosphatases (DUSPs) belong to the family of protein tyrosine phosphatases, which can dephosphorylate both serine/threonine and tyrosine residues. During the past decades, DUSPs have been implicated in various physiological and pathological activities. Besides mitogen-activated protein kinases (MAPKs) as the main substrates, other protein and nonprotein substrates can also be dephosphorylated by DUSPs. Aberrant regulations of DUSPs have been found in various diseases such as cancer, neurological disorders, and kidney diseases, suggesting the involvement of DUSPs in the pathogenesis of diseases. Summary: In this review, we summarize the general characteristics of DUSPs and the research progress made in the field of kidney diseases, including diabetic nephropathy, hypertensive nephropathy, chronic kidney disease, acute kidney injury, and lupus nephritis. As the main biochemical function of DUSPs is to dephosphorylate MAPKs activity, decreased DUSPs are found in kidney disease models, whereas forced DUSPs expression reverses the disease presentation, which was proved by using transgenic or gene knockout model. Key Messages: Mounting evidence demonstrates that DUSPs have essential physiological and pathological functions in kidney disease. Fully understanding the functions and mechanisms of DUSPs in kidney disease contributes to their clinical application in translation medicine.
{"title":"Dual-Specificity Phosphatases and Kidney Diseases","authors":"Haiyang Li, Jiachuan Xiong, Yupei Du, Yinghui Huang, Jinghong Zhao","doi":"10.1159/000520142","DOIUrl":"https://doi.org/10.1159/000520142","url":null,"abstract":"Background: Dual-specificity phosphatases (DUSPs) belong to the family of protein tyrosine phosphatases, which can dephosphorylate both serine/threonine and tyrosine residues. During the past decades, DUSPs have been implicated in various physiological and pathological activities. Besides mitogen-activated protein kinases (MAPKs) as the main substrates, other protein and nonprotein substrates can also be dephosphorylated by DUSPs. Aberrant regulations of DUSPs have been found in various diseases such as cancer, neurological disorders, and kidney diseases, suggesting the involvement of DUSPs in the pathogenesis of diseases. Summary: In this review, we summarize the general characteristics of DUSPs and the research progress made in the field of kidney diseases, including diabetic nephropathy, hypertensive nephropathy, chronic kidney disease, acute kidney injury, and lupus nephritis. As the main biochemical function of DUSPs is to dephosphorylate MAPKs activity, decreased DUSPs are found in kidney disease models, whereas forced DUSPs expression reverses the disease presentation, which was proved by using transgenic or gene knockout model. Key Messages: Mounting evidence demonstrates that DUSPs have essential physiological and pathological functions in kidney disease. Fully understanding the functions and mechanisms of DUSPs in kidney disease contributes to their clinical application in translation medicine.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"13 1","pages":"13 - 25"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78199210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue-ru Zhao, Yue Lang, Mingchao Zhang, S. Liang, Xiaodong Zhu, Zhihong Liu
Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.
{"title":"miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury","authors":"Yue-ru Zhao, Yue Lang, Mingchao Zhang, S. Liang, Xiaodong Zhu, Zhihong Liu","doi":"10.1159/000520140","DOIUrl":"https://doi.org/10.1159/000520140","url":null,"abstract":"Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"59 1","pages":"137 - 147"},"PeriodicalIF":3.7,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84273029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryohei Miyamoto, Akinari Sekine, T. Fujimaru, Tatsuya Suwabe, H. Mizuno, E. Hasegawa, M. Yamanouchi, Motoko Chiga, Takayasu Mori, E. Sohara, S. Uchida, N. Sawa, Y. Ubara, J. Hoshino
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease and is well known to have extrarenal complications. Cardiovascular complications are of particular clinical relevance because of their morbidity and mortality; however, unclear is why they occur so frequently in patients with ADPKD and whether they are related to the genotypes. Methods: We extracted and retrospectively analyzed clinical data on patients with ADPKD who underwent echocardiography and whose genotype was confirmed by genetic testing between April 2016 and December 2020. We used next-generation sequencing to compare cardiac function, structural data, and the presence of cardiac valvular disease in patients with 1 of 3 genotypes: PKD1, PKD2, and non-PKD1, 2. Results: This retrospective study included 65 patients with ADPKD. Patients were divided into 3 groups: PKD1, n = 32; PKD2, n = 12; and non-PKD1, 2, n = 21. The prevalence of mitral regurgitation (MR) was significantly higher in the PKD1 group than in the PKD2 and non-PKD1, 2 group (46.9% vs. 8.3% vs. 19.0%, respectively; p = 0.02). In contrast, no significant difference was found for other cardiac valve complications. Conclusion: This study found a significantly higher prevalence of MR in patients with the PKD1 genotype than in those with the PKD2 or non-PKD1, 2 genotypes. Physicians may need to perform echocardiography earlier and more frequently in patients with ADPKD and the PKD1 genotype and to control fluid volume and blood pressure more strictly in these patients to prevent future cardiac events.
背景:常染色体显性多囊肾病(ADPKD)是最常见的遗传性多囊肾病，通常有肾外并发症。心血管并发症因其发病率和死亡率而具有特殊的临床意义;然而，目前尚不清楚为什么它们在ADPKD患者中如此频繁地发生，以及它们是否与基因型有关。方法:我们提取并回顾性分析2016年4月至2020年12月期间接受超声心动图检查并经基因检测确认基因型的ADPKD患者的临床资料。我们使用新一代测序来比较3种基因型(PKD1、PKD2和非PKD1、2)中1种基因型患者的心功能、结构数据和心脏瓣膜疾病的存在。结果:本回顾性研究纳入65例ADPKD患者。患者分为3组:PKD1组，n = 32;PKD2, n = 12;非pkd1, 2, n = 21。PKD1组的二尖瓣反流(MR)发生率明显高于PKD2组和非PKD1, 2组(分别为46.9%、8.3%和19.0%;P = 0.02)。相比之下，其他心脏瓣膜并发症无显著差异。结论:本研究发现PKD1基因型患者MR患病率明显高于PKD2或非PKD1, 2基因型患者。对于患有ADPKD和PKD1基因型的患者，医生可能需要更早、更频繁地进行超声心动图检查，并更严格地控制这些患者的液量和血压，以防止未来发生心脏事件。
{"title":"Echocardiographic Findings and Genotypes in Autosomal Dominant Polycystic Kidney Disease","authors":"Ryohei Miyamoto, Akinari Sekine, T. Fujimaru, Tatsuya Suwabe, H. Mizuno, E. Hasegawa, M. Yamanouchi, Motoko Chiga, Takayasu Mori, E. Sohara, S. Uchida, N. Sawa, Y. Ubara, J. Hoshino","doi":"10.1159/000520300","DOIUrl":"https://doi.org/10.1159/000520300","url":null,"abstract":"Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease and is well known to have extrarenal complications. Cardiovascular complications are of particular clinical relevance because of their morbidity and mortality; however, unclear is why they occur so frequently in patients with ADPKD and whether they are related to the genotypes. Methods: We extracted and retrospectively analyzed clinical data on patients with ADPKD who underwent echocardiography and whose genotype was confirmed by genetic testing between April 2016 and December 2020. We used next-generation sequencing to compare cardiac function, structural data, and the presence of cardiac valvular disease in patients with 1 of 3 genotypes: PKD1, PKD2, and non-PKD1, 2. Results: This retrospective study included 65 patients with ADPKD. Patients were divided into 3 groups: PKD1, n = 32; PKD2, n = 12; and non-PKD1, 2, n = 21. The prevalence of mitral regurgitation (MR) was significantly higher in the PKD1 group than in the PKD2 and non-PKD1, 2 group (46.9% vs. 8.3% vs. 19.0%, respectively; p = 0.02). In contrast, no significant difference was found for other cardiac valve complications. Conclusion: This study found a significantly higher prevalence of MR in patients with the PKD1 genotype than in those with the PKD2 or non-PKD1, 2 genotypes. Physicians may need to perform echocardiography earlier and more frequently in patients with ADPKD and the PKD1 genotype and to control fluid volume and blood pressure more strictly in these patients to prevent future cardiac events.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"34 1","pages":"246 - 252"},"PeriodicalIF":3.7,"publicationDate":"2021-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76992277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiuyu Li, Fei Liu, Xiaoxiao Tang, Haidong Fu, Jianhua Mao
Background: The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. Summary: HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. Key Messages: In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.
{"title":"Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism","authors":"Qiuyu Li, Fei Liu, Xiaoxiao Tang, Haidong Fu, Jianhua Mao","doi":"10.1159/000520141","DOIUrl":"https://doi.org/10.1159/000520141","url":null,"abstract":"Background: The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. Summary: HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. Key Messages: In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"52 1","pages":"44 - 56"},"PeriodicalIF":3.7,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84312650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acknowledgement to the Reviewers","authors":"","doi":"10.1159/000519978","DOIUrl":"https://doi.org/10.1159/000519978","url":null,"abstract":"","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"62 1","pages":"521 - 522"},"PeriodicalIF":3.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87025083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunsun Dai – Nanjing Medical University, Nanjing, China Zheng Dong – Augusta University, Augusta, GA, USA Chuan-Ming Hao – Fudan University, Shanghai, China John Cijiang He – Icahn School of Medicine at Mount Sinai, New York, NY, USA Gui-Sen Li – Sichuan Provincial People’s Hospital, Sichuan, China Jing Nie – Southern Medical University, Guangzhou, China Jan Novak – University of Alabama at Birmingham, Birmingham, AL, USA Fan Yi – Shandong University, Jinan, China Shengqiang Yu – Second Military Medical University, Shanghai, China Aihua Zhang – Nanjing Medical University, Nanjing, China Hong Zhang – Peking University, Beijing, China Jinghong Zhao – Third Military Medical University, Chongqing, China
{"title":"Contents Vol. 7, 2021","authors":"J. Kopp","doi":"10.1159/000519990","DOIUrl":"https://doi.org/10.1159/000519990","url":null,"abstract":"Chunsun Dai – Nanjing Medical University, Nanjing, China Zheng Dong – Augusta University, Augusta, GA, USA Chuan-Ming Hao – Fudan University, Shanghai, China John Cijiang He – Icahn School of Medicine at Mount Sinai, New York, NY, USA Gui-Sen Li – Sichuan Provincial People’s Hospital, Sichuan, China Jing Nie – Southern Medical University, Guangzhou, China Jan Novak – University of Alabama at Birmingham, Birmingham, AL, USA Fan Yi – Shandong University, Jinan, China Shengqiang Yu – Second Military Medical University, Shanghai, China Aihua Zhang – Nanjing Medical University, Nanjing, China Hong Zhang – Peking University, Beijing, China Jinghong Zhao – Third Military Medical University, Chongqing, China","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"1 1","pages":"I - VI"},"PeriodicalIF":3.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87925781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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