Kremezin (AST-120) / Mitsubishi Tanabe, Kureha Corp - LARVOL DELTA

Uremic Toxins, Chronic Kidney Disease, and Cognitive Dysfunction. (PubMed, J Am Soc Nephrol) - "Reviewed therapeutic interventions include: AST-120 [indoxyl sulfate absorbent], CH-223191 [aryl hydrocarbon receptor antagonist], TRAM34 [Kca3.1-specific inhibitor], anakinra [IL-1R inhibitor], marimastat, exercise, supplements, and kidney transplantation. Finally, future research directions are suggested including targeting of cellular senescence abundance with senotherapeutics and capitalizing on anti-inflammatory effects of regenerative, cell-based therapeutics (e.g. mesenchymal stem cells and extracellular vesicles), and use of aged murine models. Collectively, CKD-associated cognitive impairment represents a prevalent condition for which remaining knowledge gaps exist, and scientific advancements are needed to preserve cognitive function and improve the lives of in individuals with CKD."

Journal • Alzheimer's Disease • Chronic Kidney Disease • CNS Disorders • Cognitive Disorders • Inflammation • Nephrology • Renal Disease • Transplantation • Vascular Neurology • IL1R1

Impact of using oral spherical carbon adsorbent in predialysis chronic kidney disease period on cardiovascular outcome after dialysis therapy. (PubMed, Sci Rep) - "The oral spherical carbon adsorbent (OSCA), AST-120, has demonstrated efficacy in slowing the progression of chronic kidney disease (CKD)...Additionally, the OSCA ≥ 4 months group experienced significantly fewer composite outcome (HR 0.46, 95% CI 0.24-0.90). These findings indicate that longer-term OSCA use before dialysis initiation could reduce cardiovascular events and death post-dialysis, suggesting a potential 'legacy effect'."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder. (PubMed, Kidney Int) - "The altered p62 /SQSTM1 and LC3-II expression was consistent with impaired mitophagy machinery, and the effects of uremic toxins were reversible by rapamycin. A causal link between uremic toxins and the development of mitochondrial abnormalities and ROD was established by showing that a mitochondria-targeted antioxidant (MitoQ) and the charcoal adsorbent AST-120 were able to mitigate the uremic toxin-induced mitochondrial changes and improve bone health...Targeting uremic toxins, oxygen-free radical production and the mitophagy process may offer novel routes for intervention to preserve bone health in patients with CKD-MBD. This would be timely as our current armamentarium of anti-fracture medications for patients with severe CKD-MBD is limited."

Journal • Chronic Kidney Disease • Metabolic Disorders • Musculoskeletal Diseases • Nephrology • Orthopedics • Osteoporosis • Renal Disease • ATG7 • SQSTM1

The Ability of AST-120 to Lower the Serum Indoxyl Sulfate Level Improves Renal Outcomes and the Lipid Profile in Diabetic and Nondiabetic Animal Models of Chronic Kidney Disease: A Meta-Analysis. (PubMed, Toxins (Basel)) - "AST-120 lowered serum IS and triglyceride levels and improved renal function in animal models of CKD independent of diabetes status. However, AST-120's ability to lower the total cholesterol level was more prominent in animals with diabetic CKD."

Clinical • Journal • Preclinical • Retrospective data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Now You See Me, Now You Don't: Spontaneous Remission of HCC (ACG 2024) - "Labs were notable for chronic HBV co-infection with Hepatitis D, HBV viral load of 60 IU/mL, ALT 91 U/L, AST 120 U/L, total bilirubin 1.4 mg/dL, AFP of 1429 ng/mL...He was referred to medical oncology, who recommended lenvatinib for treatment of unresectable HCC...During this interval, he was started on entecavir 0.5 mg daily for treatment of chronic HBV...MRI abdomen in 11/2017 demonstrated a 93 mm, ill-defined heterogenous mass involving the right lobe of the liver, predominantly in segment 5, 6 and 8 (A). By 12/2018, this mass was no longer recognized (B), and remained as such in 12/2019 (C) and on most recent imaging in 11/2023 (D)."

Clinical • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Pain • Systemic Inflammatory Response Syndrome • Thrombosis • CD4 • IL2 • TNFA

AST-120 Protects Cognitive and Emotional Impairment in Chronic Kidney Disease Induced by 5/6 Nephrectomy. (PubMed, Brain Sci) - "Our findings demonstrate the potential therapeutic effects of AST-120 in lowering IS levels and improving cognitive and emotional impairments associated with CKD."

Journal • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Cognitive Disorders • Mood Disorders • Nephrology • Psychiatry • Renal Disease • GFAP

Plasmablastic Lymphoma in the Duodenum: A Rare and Aggressive disease (ACG 2024) - "He was found to be intermittently febrile, and initial laboratory studies were significant for WBC 1.82 K/μL, Hb 6.0 g/dL, platelets 41 K/μL, alkaline phosphatase 603 U/L, AST 120 U/L, ALT 62 U/L, total bilirubin 0.8 mg/dL, CD4 98 cells/μL, and HIV viral load 2,700,455...Figure 2 (right) reveals Endoscopic findings on initial EGD of near-obstructing mass in duodenal sweep and 2nd portion of duodenum. Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Liver Failure • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • CD4

A Challenging Diagnosis of Low-grade Appendiceal Mucinous Neoplasm Mimicking Ovarian Cancer and Primary Biliary Cholangitis (ACG 2024) - "Labs showed WBC 12.8 k/mm3, lactic acid 2.4 mmol/l, creatinine 5.43 mg/dl (baseline 0.7 mg/dl), AST 120 iu/l, ALT 58 u/l, alkaline phosphatase 468 u/l, and total bilirubin 6.7 mg/dl...Additionally, colorectal cancer should be excluded with a colonoscopy in these patients due to the associated risks. Figure: A. Magnetic Resonance Imaging of the Abdomen and Pelvis without contrast showing moderate to large amounts of abdominal ascites."

Acute Kidney Injury • Appendix Cancer • Colorectal Cancer • Gynecology • Hepatology • Immunology • Nephrology • Oncology • Ovarian Cancer • Primary Biliary Cholangitis • Renal Disease • Solid Tumor • CA 19-9 • MUC16

Effect of Oral Absorbent Therapy on Kidney Progression According to the Cause of CKD (KIDNEY WEEK 2024) - "Changes in Serum Cr Before and After Drug Therapy Over One Year in Each Etiology Group Background: Oral absorbent therapy with DW-7202 (Renemezin®) and AST-120 (Kremezin®) slows the progression of CKD... These findings suggest that oral absorbent therapy has different effects depending on the cause of CKD. The treatment significantly alleviated CKD progression in patients with HTN, DM, ADPKD, and unknown etiology compared to those with GN."

Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Polycystic Kidney Disease

AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis. (PubMed, Mol Med) - "In conclusion, AST-120 alleviates renal IRI via suppressing HK2-mediated glycolysis, which suppresses H3K18 lactylation and further reduces HK2 levels. This study proposes a novel mechanism by which AST-120 alleviates IRI."

Journal • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury • HK2

Electrospun EVOH/AST-120 hybrid nanofiber membranes for removal of indoxyl sulfate from blood. (PubMed, RSC Adv) - "Furthermore, the nanofibers successfully reduced the IS concentration in the blood under circulating conditions. Therefore, these EVOH/AST-120 nanofibers are expected to greatly improve the prognosis of patients with CKD when used in combination with the current hemodialysis therapy as an IS-adsorbing filter."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

A case of chronic kidney disease with refractory periodic vomiting and hypertension in a pediatric patient. (PubMed, CEN Case Rep) - "In Japan, the uremic toxin adsorbent AST-120 and angiotensin-converting enzyme inhibitor-I (ACE-I) are not strongly recommended for CKD patients...However, our patient had low serum levels of proinflammatory cytokines, and his serum levels of the chemokines CX3CL1 and CCL2 decreased with age, together with improvement in his clinical course. Therefore, some specific chemokines might be diagnostic and/or prognostic biomarkers of CKD."

Journal • Atherosclerosis • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Gastrointestinal Disorder • Hypertension • Nephrology • Pediatrics • Renal Disease • CCL2 • CX3CL1

Pharmacologic therapeutics in sarcopenia with chronic kidney disease. (PubMed, Kidney Res Clin Pract) - "Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. AST-120 prevented IS and PCA 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."

Journal • Chronic Kidney Disease • Inflammation • Metabolic Disorders • Muscular Atrophy • Nephrology • Renal Disease • Sarcopenia • Targeted Protein Degradation

AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients. (PubMed, Aging (Albany NY)) - "This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment."

Journal • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease • TNFA

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120. (PubMed, Heliyon) - "FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD."

Journal • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease

Effects of AST-120 on mortality in patients with chronic kidney disease modeled by artificial intelligence or traditional statistical analysis. (PubMed, Sci Rep) - "In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Lifestyle factors associated with a rapid decline in the estimated glomerular filtration rate over two years in older adults with type 2 diabetes-Evidence from a large national database in Japan. (PubMed, PLoS One) - "We found specific lifestyle risk factors were associated with a rapid eGFR decline among people with type 2 diabetes from a nationwide database in Japan. The associations varied by baseline eGFR level, age, and sex. Lifestyle modifications may effectively prevent the aggravation of diabetic kidney disease."

Journal • Cardiovascular • Diabetes • Diabetic Nephropathy • Dyslipidemia • Heart Failure • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Inhibition of Indoxyl Sulfate-Induced Reactive Oxygen Species-Related Ferroptosis Alleviates Renal Cell Injury In Vitro and Chronic Kidney Disease Progression In Vivo. (PubMed, Antioxidants (Basel)) - "The effects of IS-induced ROS generation, lipid peroxidation, ferroptosis, senescence, ER stress, and injury/fibrosis were effectively alleviated by treatments with an iron chelator deferoxamine (DFO) in vitro and the adsorbent charcoal AST-120 (scavenging the IS precursor) in vivo. Our findings suggest that IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys. AST-120 administration may serve as a potential therapeutic strategy."

Journal • Preclinical • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease

The Uremic Toxin Indoxyl Sulfate Contributes to Renal Fibrosis via mTORC1 Signaling Pathway (KIDNEY WEEK 2023) - "The findings reported herein indicate that IS activates mTORC1, which then contributes to renal fibrosis. Therapeutic interventions targeting IS and mTORC1 could be effective against renal fibrosis in CKD."

Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease

An Accordion-Like Bile Duct in IgG4-Related Sclerosing Cholangitis: A Rare Finding in an Elusive Diagnosis! (ACG 2023) - "Laboratory findings were notable for AST 120 U/L, ALT 191 U/L, alkaline phosphatase 170 U/L, and bilirubin 6.4 mg/dl...1c. Spyglass cholangioscopy: Erythematous biliary mucosa."

Fibrosis • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pancreatic Cancer • Pancreatitis • Solid Tumor

Sepsis associated with sodium glucose co-transporter 2 inhibitor in an elderly patient with chronic kidney disease. (PubMed, Geriatr Gerontol Int) - No abstract available

Journal • Chronic Kidney Disease • Infectious Disease • Nephrology • Renal Disease • Septic Shock

AST-120 in Hemodialysis Patients With Uremic Pruritus (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: Conmed Pharmaceutical & Bio-Medical Corporation | Recruiting ➔ Completed | Phase classification: PN/A ➔ P4 | N=150 ➔ 100

Enrollment change • Phase classification • Trial completion • Dermatology • Pruritus • Renal Disease • B2M • CRP • IL6 • TNFA

Combined aspartate aminotransferase level and PE-SARD score predict 1-month bleeding risk in acute pulmonary embolism. (PubMed, Am J Med Sci) - "In PE patients, AST is an independent factor in predicting the 1-month bleeding risk, and a novel joint model that combines AST and PE-SARD score improved the predictive efficiency for the 1-month bleeding risk."

Journal • Cardiovascular • Hepatology • Liver Failure • Pulmonary Embolism • Respiratory Diseases

Factors associated with gait speed: results from the RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients (RECOVERY) study. (PubMed, Kidney Res Clin Pract) - "In the multivariate linear regression analysis adjusted for age, sex, diabetes mellitus, and estimated glomerular filtration rate, insurance status, handgrip strength, IL-6 level, hemoglobin level, mental component scale score, and physical component scale score were significantly associated with gait speed. In conclusion, gait speed is associated with handgrip strength, IL-6 level, and various components of quality of life in predialysis chronic kidney disease patients."

Journal • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Sarcopenia • IL6

Efficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment. (PubMed, Nat Commun) - "More importantly, the selective removal efficacy of indole is substantially higher than that of the commercial adsorbent AST-120 used in the clinic. The present study opens up a new avenue to eliminate indoxyl sulfate by a non-dialysis strategy and further expands the in vivo applications of covalent organic frameworks."

Journal • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Renal Disease