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( Ran-hui Cha ),( Shin Wook Kang ),( Cheol Whee Park ),( Dae Ryong Cha ),( Ki Young Na ),( Sung Gyun Kim ),( Sun Ae Yoon ),( Sejoong Kim ),( Sang Youb Han ),( Jung Hwan Park ),( Jae Hyun Chang ),( Chu 대한신장학회 2017 Kidney Research and Clinical Practice Vol.36 No.1
Background: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). Methods: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. Results: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). Conclusion: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.
Hui Ran,Yao Lu,Qi Zhang,Qiuyue Hu,Junmei Zhao,Kai Wang,Xuemei Tong,Qing Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.3
Background: Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear. Methods: We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle. Results: MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake. Conclusion: MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.
Pharmacologic therapeutics in sarcopenia with chronic kidney disease
( Ran-hui Cha ) 대한신장학회 2024 Kidney Research and Clinical Practice Vol.43 No.2
Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.
Ran-hui Cha,Su Hyun Kim,Eun Hui Bae,유민아,Beom Soon Choi,최훈영,Sun Woo Kang,Jung-Ho Shin,한상엽,양철우,강덕희 대한신장학회 2019 Kidney Research and Clinical Practice Vol.38 No.3
Background: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. Methods: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. Results: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serumuric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). Conclusion: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebrocardiovascular complications.
( Ran-hui Cha ),( Hajeong Lee ),( Jung Pyo Lee ),( Young Rim Song ),( Sung Gyun Kim ),( Yon Su Kim ) 대한신장학회 2017 Kidney Research and Clinical Practice Vol.36 No.4
Background: Blood pressure (BP) control is the most-established method for the prevention of chronic kidney disease (CKD) progression. However, the ideal BP target for CKD patients is still under debate. Methods: We performed a survey of regular registered members of the Korean Society of Nephrology to determine physician perceptions of BP control in patients with CKD. In addition, we evaluated the target BP achievement rate using data from the APrODiTe-2 study. Results: Two-thirds of physicians considered the target BP for CKD to be < 130/85 mmHg. The systolic BP (SBP) thresholds for diabetic CKD, proteinuria ≥ 300 mg/day, 30 ≤ glomerular filtration rate (GFR) < 60 mL/min/1.73 m<sup>2</sup>, age < 60 years, and the presence of atherosclerotic (ASO) complications were significantly lower than the SBP thresholds of the opposite parameters. The three major hurdles to controlling BP were non-compliance with lifestyle modification and medications, and self-report of well-controlled home BP. Most physicians prescribed home and ambulatory BP monitoring to less than 50% of their patients. The target BP achievement rates using the SBP thresholds in this survey were as follows: non-diabetic (69.3%); diabetic (29.5%); proteinuria < 300 mg/day (72.3%); proteinuria > 300 mg/day (33.7%); GFR ≥ 60 (76.4%); GFR < 30 (47.8%); no evidence of ASO (67.8%); and the presence of ASO (42.9%). Conclusion: The target BP was lower in patients with higher cerebro-cardiovascular risks. These patient groups also showed lower target BP achievement rates. We also found a relatively lower application and clinical reflection rate of home or ambulatory BP monitoring.
( Ran Hui Cha ),( Ha Jeong Lee ),( Soo Hee Kim ),( Eun Jung Jung ),( Kyung Chul Moon ),( Yon Su Kim ) 대한신장학회 2010 Kidney Research and Clinical Practice Vol.29 No.1
We report a case of microscopic polyangiitis, presenting with rapidly progressive glomerulonephritis, neuropsychiatric abnormalities, and urticarial vasculitis. A 65-year-old woman reported loss of appetite, significant weight loss, and a transient history of veering tendency. She was presented with a mild fever, cough, and sputum. Routine laboratory test revealed anemia, leukocytosis with a left shift, azotemia, and elevated highly sensitive C-reactive protein. The bilateral kidneys were observed to be enlarged (right kidney 16.3 cm, left kidney 18.2 cm) on an abdominal computed tomography. The perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) titer was >1:640 and MPO-ANCA was positive. Her chief complaints consisted of character change, visual illusion, and hearing loss. A skin rash with a bullous change resembling urticaria was further developed. Kidney biopsy demonstrated pauci-immune diffuse crescentic glomerulonephritis. Skin biopsy was compatible with urticarial vasculitis. Having received intravenous cyclophosphamide and oral prednisolone, she showed sustained improvement in renal function, as well as her neuropsychiatric symptoms and skin rash.