tolvaptan / Generic mfg. - LARVOL DELTA

PaO2/FiO2 Ratio As an Exploratory Indicator of Oxygenation Changes in Acute Decompensated Heart Failure Treated with Intravenous Tolvaptan. (PubMed, CJC Open) - "In ADHF, use of adjunctive intravenous TLV was associated with improved early oxygenation and diuresis without an apparent increase in short-term adverse events. These exploratory findings suggest that intravenous TLV may be a useful component of acute decongestive therapy, warranting prospective validation."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Disease

CDK4/6 Inhibitor Abemaciclib Arrests and Reverses Kidney Cyst Progression in Preclinical Models of Autosomal Dominant Polycystic Kidney Disease. (PubMed, J Am Soc Nephrol) - "Abemaciclib has greater therapeutic efficacy and tolerability than tolvaptan in this preclinical model, largely driven by CDK6 inhibition-mediated restoration of axonemal polyglutamylation and increased ciliary polycystin abundance."

Journal • Preclinical • Autosomal Dominant Polycystic Kidney Disease • Fibrosis • Genetic Disorders • Immunology • Nephrology • Oncology • Polycystic Kidney Disease • Renal Disease • CDK6

Association Between Tolvaptan Exposure and Venous Thromboembolism Risk in ADPKD: A Real-World Propensity-Matched EHR Study. (PubMed, Nephrology (Carlton)) - "In this large propensity-matched real-world cohort, tolvaptan exposure was associated with lower risks of VTE and mortality among patients with ADPKD. Given the retrospective observational design and the possibility of residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than causal. Further prospective studies incorporating imaging-based measures of disease severity are warranted."

Journal • Real-world evidence • Retrospective data • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Genetic Disorders • Hematological Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • Respiratory Diseases • Venous Thromboembolism

Feasibility and safety of intravenous tolvaptan administration immediately upon ICU admission after cardiac surgery with cardiopulmonary bypass. (PubMed, Surg Today) - "In this selected cohort, intravenous TSP administration immediately upon ICU admission after cardiac surgery with cardiopulmonary bypass was feasible and not associated with any major safety concerns, including in patients with a reduced renal function. TSP also tended to reduce day-to-day fluid balance fluctuations with an adequate urine output."

Journal • Acute Kidney Injury • Cardiovascular • Critical care • Nephrology • Renal Disease

Tolvaptan in heart failure: Contemporary evidence and a framework for precision decongestion. (PubMed, Heart Fail Rev) - "The complementary roles of oral and intravenous formulations and evidence in selected clinical settings are also discussed. Current data support tolvaptan as a monitored adjunct for selected patients, not as routine therapy or a treatment with established prognostic benefit."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Disease

Oral urea as a safety strategy in complex syndrome of inappropriate antidiuretic hormone secretion - Challenges posed by polypharmacy and institutionalization (PubMed, Nutr Hosp) - "this case highlights oral urea as a safe, effective, and cost-effective therapeutic option for SIADH when fluid restriction is not feasible and vaptans are unsuitable, particularly in frail older adults with polypharmacy and complex social circumstances."

Journal • Cardiovascular • Geriatric Disorders • Heart Failure • Hepatology

Chronic hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in an elderly patient with chronic obstructive pulmonary disease: Favorable response to oral urea (PubMed, Nutr Hosp) - "fluid restriction and oral sodium supplementation were ineffective. Tolvaptan induced a rapid increase in serum sodium and was discontinued due to risk of overcorrection. Subsequently, oral urea (15 g/day) maintained serum sodium levels within the normal range throughout follow-up. In conclusion, this case supports oral urea as an effective, safe, and cost-efficient therapeutic option for chronic SIADH, particularly in elderly patients in whom vasopressin V2 receptor antagonists may carry a risk of overly rapid correction."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Depression • Heart Failure • Immunology • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Safety and efficacy of tolvaptan sodium phosphate in patients undergoing open-heart surgery. (PubMed, Surg Today) - "Intravenous TSP can induce a rapid and sustained diuretic response following open-heart surgery, and the serum sodium levels determine the magnitude of the aquaretic response to intravenous TSP."

Journal • Cardiovascular

Phase Ib study of intravenous HRS-9057, an arginine vasopressin V2 receptor antagonist, versus oral tolvaptan in congestive heart failure with volume overload despite prior diuretic therapy (ESC 2026) - "Both HRS-9057 groups maintained a negative fluid balance throughout the 7-day treatment, whereas the tolvaptan group exhibited a negative balance only on Day 1 (Figure 2). Comparable elevations in serum sodium were observed across all groups, with values remaining within the normal range.ConclusionIn CHF patients with persistent volume overload, intravenous HRS-9057 showed a trend toward greater body weight reduction and decongestive effects compared with oral tolvaptan, with no new safety concerns."

P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

Efficacy and safety of our unique clinical pathway for acute care that specifies early introduction of tolvaptan in elderly patients with congestive heart failure: a 10-year study (ESC 2026) - "Our original clinical pathway for acute care of congestive heart failure, which prescribes the use of tolvaptan immediately after admission with the aim of early mobilization through early diuresis, had been in place for 10 years, and its usefulness in clinical progression had been confirmed even in elderly patients. The safety of the active use of tolvaptan in these patients was also acceptable, but as rare events can occur, careful attention should be paid to acute clinical data."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Universal pipeline for high-resolution GPCR structure determination. (PubMed, Nat Struct Mol Biol) - "NOAH enabled structure determination of vasopressin V2 receptor bound to the antagonist tolvaptan or partial agonist OPC51803 and bradykinin B2 receptor bound to the antagonist icatibant, revealing receptor activation and inhibition mechanisms. Coupling NOAH to ARK1 improved the V2 receptor-tolvaptan map and enabled high-resolution structures of lysophosphatidic acid receptor 2 bound to Ki16425 and free fatty acid receptor 2 bound to GLPG0974. NOAH-ARK1 minimizes trial-and-error construct optimization and provides a broadly applicable route for GPCR structural analysis and drug discovery."

Journal • AURKA

Questioning the kidney-protective effects of tolvaptan: a testable hypothesis to revisit the current narrative. (PubMed, Open Res Eur) - "Across all trials, sensitivity analyses using contemporary modelling strategies are warranted to strengthen confidence in eGFR slope as a regulator-endorsed clinical endpoint. Improving the methodological rigour with which treatment effects are estimated is essential to ensure that clinical decisions accurately reflect therapeutic benefit relative to treatment burden and patient experience."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • CST3

TVU Trial: Tolvaptan versus Urea in acutely hospitalised patients with low blood sodium concentration (ANZCTR) - P3 | N=112 | Recruiting | Sponsor: University of Melbourne | Not yet recruiting ➔ Recruiting

Enrollment open

Comment on Yamazaki et al. Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy. Int. J. Mol. Sci. 2024, 25, 2088. (PubMed, Int J Mol Sci) - "In response to the article [...]."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Association of semaglutide use with kidney outcomes in adults with ADPKD: A propensity score-matched real-world study. (PubMed, Sci Prog) - "Patients receiving sodium-glucose cotransporter-2 inhibitors, tolvaptan, or other glucagon-like peptide-1 receptor agonists were excluded...Because semaglutide-induced weight loss and reductions in muscle mass may lower serum creatinine independently of true glomerular filtration, the observed preservation of creatinine-based eGFR should be interpreted cautiously. Given the observational design, limited follow-up, and potential residual confounding, these findings should be considered hypothesis-generating and require confirmation in prospective studies."

Journal • Real-world evidence • Retrospective data • Acute Kidney Injury • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Genetic Disorders • Infectious Disease • Nephrology • Polycystic Kidney Disease • Renal Disease

Targeted analysis of salicylate binding partners in renal epithelial cells reveals major AMPK dependency. (PubMed, Biochim Biophys Acta Mol Cell Res) - "With the current treatment tolvaptan not suited for the majority of patients, an urgent need remains for novel therapeutics. However, we also observed that salicylate induces mitochondrial uncoupling and inhibition of heme synthesis, while other AMPK activators do not, revealing AMPK-independent effects of salicylate in cystic disease. These results provide us with further insights into the working mechanisms of salsalate/salicylate and offer a solid basis for the future development of salsalate as a potential therapeutic for ADPKD."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Inflammation • Nephrology • Polycystic Kidney Disease • Renal Disease • AMPK • PKD1 • PRKD1

Perioperative Vasopressor Resistance in a Patient Taking Tolvaptan: A Multi-Mechanism Hemodynamic Challenge (ASA 2026) - "A 55-year-old male with autosomal dominant polycystic kidney disease, secondary hyperparathyroidism, and hypertension treated with tolvaptan, carvedilol, losartan, and amlodipine developed severe intraoperative bradycardia followed by hypotension. These interacting mechanisms may significantly blunt conventional therapies for bradycardia and hypotension. Early recognition and prompt administration of direct α1/β1 agonists such as epinephrine may be critical for restoring intraoperative hemodynamic stability."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Endocrine Disorders • Genetic Disorders • Hypertension • Hypotension • Nephrology • Polycystic Kidney Disease • Renal Disease • Secondary Hyperparathyroidism

Can MQ232 guide to novel options for treatment of ADPKD? (PubMed, Kidney Int) - "showcase a green mamba-derived compound, MQ232, which interferes with cyst growth in a mouse model of autosomal dominant polycystic kidney disease, similar to the only approved drug for autosomal dominant polycystic kidney disease treatment, tolvaptan. However, the authors reveal cyclic adenosine monophosphate-dependent and -independent components in MQ232's mode of action and gender differences in efficacy. Therefore, MQ232 may pave the way to novel treatment options for autosomal dominant polycystic kidney disease."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Prognostic Performance of Ellipsoid Kidney Volume Measurement in a Computed Tomography-Heavy ADPKD Cohort: A Retrospective Observational Cohort Study. (PubMed, Can J Kidney Health Dis) - "Accurate prognostic classification in autosomal dominant polycystic kidney disease is important for risk stratification and treatment decisions, including tolvaptan eligibility...In this computed tomography-heavy cohort, the ellipsoid method showed good concordance with manual segmentation for kidney volume measurement and high specificity for identifying high-risk disease. However, systematic underestimation may lead to downward misclassification, particularly in borderline cases."

Journal • Observational data • Retrospective data • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Diuretic therapy for critically ill patients: a systematic review and network meta-analysis. (PubMed, Ann Intensive Care) - "Evaluated interventions included bolus loop diuretics (19 studies), continuous loop infusion (15 studies), oral loop diuretics (5 studies), and loop diuretics combined with tolvaptan (8 studies), spironolactone (3 studies), thiazides (2 studies), acetazolamide (1 study), or triamterene (1 study). Bolus loop diuretics were at least comparable to alternate diuretic strategies for patient important outcomes in critically ill adults, but this was based mostly on low or very low certainty evidence. Tolvaptan monotherapy may decrease acute kidney injury, but its effect on subsequent need for RRT and mortality remains uncertain."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Vaptans: A Narrative Review of Pharmacokinetics, Pharmacogenetics, and Clinical Applications. (PubMed, Cells) - "This review evaluates their chemical evolution from peptide analogs to orally bioavailable molecules and summarizes the pharmacokinetic profiles of key agents, including tolvaptan, conivaptan, and mozavaptan...Furthermore, the impact of pharmacogenetic factors, especially CYP3A5 and SVEP1 polymorphisms, is explored as a potential source of inter-individual variability in treatment response. By integrating structural, metabolic, and genetic data, this article highlights the potential for personalized aquaretic therapy and identifies critical safety and monitoring protocols necessary for optimizing clinical outcomes."

Biomarker • Journal • PK/PD data • Review • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • CYP3A5 • SVEP1

SGLT2 inhibitors in autosomal dominant polycystic kidney disease: rationale, evidence gaps, and ongoing clinical trials. (PubMed, Int Urol Nephrol) - "Autosomal dominant polycystic kidney disease (ADPKD) remains the leading inherited cause of chronic kidney disease (CKD), with specific management largely relying on the approval of the selective vasopressin V2 receptor antagonist, tolvaptan, in recent years...Available observational studies indicate both beneficial and adverse effects, while ongoing trials aim to provide more definitive evidence on the safety and efficacy of SGLT2 inhibitors in this inherited CKD population. Therefore, this review aims to focus on the current treatment options for ADPKD patients and the promising role of SGLT2 inhibitors, drawing on the available literature and ongoing RCTs."

Journal • Review • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Genetic Disorders • Liver Failure • Nephrology • Polycystic Kidney Disease • Renal Disease

Renal Volume Reduction on Magnetic Resonance Imaging During Tolvaptan Therapy in Patients with ADPKD: A Case Series. (PubMed, J Nephrol) - "These findings suggest that a decrease in kidney volume may occur in some patients with ADPKD during tolvaptan therapy, highlighting the heterogeneity of treatment response and indicating that changes in kidney volume do not always parallel other clinical parameters. Larger studies are needed to better elucidate the variability in treatment response among patients."

Journal • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • Transplantation

Serum Copeptin Rises After Tolvaptan for Hyponatraemia, but Does Not Predict Risk of Rapid Sodium Rise: Pre-Specified Secondary Analysis of the TVFR Trial. (PubMed, Clin Endocrinol (Oxf)) - P3 | "Tolvaptan increased serum copeptin compared to fluid restriction. Further research is required to determine if there is clinical utility for measuring copeptin in hyponatraemia before it is adopted into practice."

Journal • Cardiovascular • Heart Failure

Severe Euvolemic Hyponatremia Consistent With Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) During Localized Herpes Zoster in an Older Adult. (PubMed, Cureus) - "As the patient became symptomatic, and hypertonic saline (with removal of fluid restriction) produced no improvement, a single dose of tolvaptan produced rapid correction of serum sodium and improvement in mentation. The patient was subsequently maintained on sodium chloride tablet supplementation, fluid restriction, and a high-protein diet, with serum sodium improving to 135-136 mEq/L. This case describes severe hypotonic euvolemic hyponatremia meeting biochemical criteria for SIADH in the setting of localized herpes zoster, after consideration of concurrent hydrochlorothiazide exposure and temporally associated oral acyclovir."

Journal • Cardiovascular • Dyslipidemia • Genito-urinary Cancer • Heart Failure • Herpes Zoster • Hypertension • Infectious Disease • Nephrology • Oncology • Pain • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Varicella Zoster