Review
Biochemistry & Molecular Biology
Anna Gluba-Sagr, Beata Franczyk, Magdalena Rysz-Gorzynska, Janusz Lawinski, Jacek Rysz
Summary: Chronic kidney disease is a significant health concern, with renal fibrosis being a major mechanism of renal dysfunction. MicroRNAs play important roles in the development of fibrosis and chronic kidney disease. However, the effects and regulation of miRNAs may vary in different tissues and cells.
Article
Pharmacology & Pharmacy
Mei-Zi Wang, Jie Wang, Dong-Wei Cao, Yue Tu, Bu-Hui Liu, Can-Can Yuan, Huan Li, Qi-Jun Fang, Jia-Xin Chen, Yan Fu, Bing-Ying Wan, Zi-Yue Wan, Yi-Gang Wan, Guo-Wen Wu
Summary: The study confirmed that FPS, similar to RAP, can alleviate RF in DKD by inhibiting NLRP3 inflammasome-mediated podocyte pyroptosis, regulating the AMPK/mTORC1/NLRP3 signaling axis. These findings provide an in-depth understanding of the pathogenesis of RF, aiding in identifying precise targets for DKD treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fatimah K. Khalaf, Chrysan J. Mohammed, Prabhatchandra Dube, Jacob A. Connolly, Apurva Lad, Usman M. Ashraf, Joshua D. Breidenbach, Robin C. Su, Andrew L. Kleinhenz, Deepak Malhotra, Amira F. Gohara, Steven T. Haller, David J. Kennedy
Summary: This study found that decreased PON-1 is associated with the progression of renal inflammation and fibrosis independent of blood pressure. By knockout of the Pon1 gene in a rat model, it was discovered that the absence of PON-1 leads to increased renal fibrosis, sclerosis, and tubular injury, as well as increased recruitment of immune cells in the renal interstitium and the expression of inflammatory genes. Furthermore, the absence of PON-1 also results in a decline in renal function and increased renal oxidative stress.
Article
Biochemistry & Molecular Biology
Anja Saalbach, Ulf Anderegg, Ralph Wendt, Joachim Beige, Anette Bachmann, Nora Kloeting, Matthias Blueher, Ming-Zhi Zhang, Raymond C. Harris, Michael Stumvoll, Anke Toenjes, Thomas Ebert
Summary: Kidney fibrosis, a major factor in chronic kidney disease (CKD), leads to irreversible organ function loss. This study investigated the association of the soluble form of Thymocyte differentiation antigen-1 (sThy-1) with clinical parameters in CKD patients receiving hemodialysis. The study also examined Thy-1 tissue expression in a mouse model of diabetic CKD. The results showed that sThy-1 levels increased with worsening renal function, regardless of the presence of diabetes. Serum creatinine was found to be a major predictor of sThy-1 levels. Additionally, sThy-1 was found to be an independent predictor of markers of renal function. The study suggests that Thy-1 may have a role in controlling kidney fibrosis and could potentially be used as a renal antifibrotic factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dentistry, Oral Surgery & Medicine
Youn Soo Lee, Ae Ri Kim, Yeong-Eui Jeon, Eun-Jung Bak, Yun-Jung Yoo
Summary: The objective of this study was to examine the effect of periodontitis on renal function and morphology in rats with or without nephrectomy-induced chronic kidney disease. The results showed that periodontitis increased renal fibrosis and inflammation, but did not affect renal function. In the presence of chronic kidney disease, periodontitis also increased TNFa expression in the kidneys.
Article
Biochemistry & Molecular Biology
Antonella La Russa, Danilo Lofaro, Alberto Montesanto, Daniele La Russa, Gianluigi Zaza, Simona Granata, Michele Di Dio, Raffaele Serra, Michele Andreucci, Renzo Bonofiglio, Anna Perri
Summary: In this study, the association of functional variants of NLRP3 pathway-related genes (NLRP3-rs10754558, CARD8-rs2043211) with CKD susceptibility was investigated for the first time. Logistic regression analyses revealed significantly higher frequencies of the G allele of NLRP3 variant (67.3%) and the T allele of CARD8 variant (70.8%) among cases compared to controls (35.9% and 31.2%, respectively). The results suggest that NLRP3 rs10754558 and CARD8 rs2043211 variants may be associated with susceptibility to CKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sandra Rayego-Mateos, Laura Marquez-Exposito, Pamela Basantes, Lucia Tejedor-Santamaria, Ana B. Sanz, Tri Q. Nguyen, Roel Goldschmeding, Alberto Ortiz, Marta Ruiz-Ortega
Summary: Inflammation is a key characteristic of kidney diseases, and the NLRP3/Inflammasome, RIPK3, and NRF2/oxidative pathways are involved in kidney inflammation regulation. CCN2 is a fibrotic biomarker and mediator of kidney damage, and its role in the NLRP3/RIPK3/NRF2 pathways has not been evaluated.
Review
Pharmacology & Pharmacy
Melanie Tepus, Elisa Tonoli, Elisabetta A. M. Verderio
Summary: Chronic kidney disease (CKD) is a global health issue affecting up to 16% of the population worldwide. If left untreated, it can progress to end-stage kidney disease (ESKD), requiring dialysis or transplantation. Kidney fibrosis, the unsuccessful wound-healing of kidney tissue, is the end point of CKD. Urinary extracellular vesicles (uEVs), which carry low-abundant proteins and large molecules, are a potential source of rare CKD biomarkers. This review discusses the diagnostic and prognostic value of uEVs biomarkers and their potential application in experimental antifibrotic therapeutics.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrei Niculae, Mihai-Emil Gherghina, Ileana Peride, Mirela Tiglis, Ana-Maria Nechita, Ionel Alexandru Checherita
Summary: Acute kidney injury (AKI) is a major cause of chronic kidney disease (CKD), leading to renal fibrosis and chronic kidney damage. Maladaptive kidney processes play a crucial role in the transition from AKI to CKD. Risk factors include the frequency and severity of kidney injury, as well as chronic diseases and unmodifiable factors. Understanding these mechanisms and risk factors is important for preventing or delaying the development of CKD from AKI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Ashish Verma, Anand Vaidya, Sonu Subudhi, Sushrut S. Waikar
Summary: The study found that higher serum aldosterone levels are independently associated with an increased risk for kidney disease progression in individuals with chronic kidney disease, regardless of concomitant diabetes. This suggests a potential role for mineralocorticoid receptor antagonists in delaying CKD progression even in those without diabetes.
EUROPEAN HEART JOURNAL
(2022)
Review
Pharmacology & Pharmacy
Jonatan Barrera-Chimal, Frederic Jaisser, Hans-Joachim Anders
Summary: Chronic kidney disease is a major public health concern globally, with MR antagonists emerging as a potential therapeutic approach against various forms of kidney disease. Experimental and clinical studies have shown the protective effects of MRAs in reducing albuminuria and slowing disease progression. Recent evidence also suggests that MRAs can reduce hard kidney outcomes, particularly in CKD associated with type 2 diabetes, highlighting their potential benefit in maximizing organ protection through combination therapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Physiology
Roberto Palacios-Ramirez, Ixchel Lima-Posada, Benjamin Bonnard, Marie Genty, Amaya Fernandez-Celis, Judith Hartleib-Geschwindner, Fabienne Foufelle, Natalia Lopez-Andres, Krister Bamberg, Frederic Jaisser
Summary: Obesity and metabolic diseases are linked to chronic kidney disease, and mineralocorticoid receptor antagonists have shown potential in treating non-diabetic chronic kidney disease associated with metabolic diseases. This study used a mouse model to demonstrate the beneficial effects of the mineralocorticoid receptor antagonist canrenoate in improving metabolic function and reducing proteinuria in chronic kidney disease mice, while also preventing the detrimental effects of a high fat diet on renal fibrosis and inflammation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Satoyasu Ito, Eri Manabe, Yi Dai, Masaharu Ishihara, Takeshi Tsujino
Summary: The study suggests that Juzentaihoto (TJ-48) may exert a renal protective effect in mice with adenine-induced chronic kidney disease by suppressing fibrosis and inflammation.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alice Barinotti, Massimo Radin, Irene Cecchi, Silvia Grazietta Foddai, Elena Rubini, Dario Roccatello, Savino Sciascia
Summary: Chronic kidney disease is a widely prevalent pathological condition with a significant impact on patients' quality of life. Renal fibrosis, the main biological mechanism underlying CKD, poses challenges for therapeutic strategies. Kidney biopsy is currently the best tool for assessing renal fibrosis, but non-invasive biomarkers are needed. Systematic review of serological markers associated with renal fibrosis in CKD patients over the past five years showed scattered evidence, highlighting the complexity of the fibrotic process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Li-Ting Tsai, Te- Weng, Ting-Yu Chang, Kuo-Cheng Lan, Chih-Kang Chiang, Shing-Hwa Liu
Summary: The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). Exposure to IS can induce ferroptosis, characterized by iron accumulation, impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys.