tolvaptan / Generic mfg. - LARVOL DELTA

Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. (PubMed, Kidney360) - "Tolvaptan, a vasopressin V2 receptor antagonist, established cAMP modulation as a disease-modifying strategy but is limited by aquaretic effects and hepatotoxicity risk...Gene-directed therapies aim to restore polycystin dosage, including anti-miR-17 oligonucleotides (e.g., farabursen) and pharmacochaperones that rescue misfolded PC1 and restore trafficking in select PKD1 missense variants (e.g., VX-407)...Metabolic reprogramming is targeted by agents such as metformin, bempedoic acid, GLP-1 receptor agonists, and structured dietary interventions...Collectively, these advances signal a transition toward a layered, mechanism-guided framework in which vasopressin blockade is integrated with metabolic, other signaling, and genotype-specific therapies. As biomarkers and risk stratification tools mature, ADPKD management is poised to become increasingly precise, tolerable, and effective."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • IGF1 • MIR17 • PKD1 • PRKD1

Syndrome of Inappropriate Secretion of Antidiuretic Hormone in a Dog With Meningoencephalitis of Unknown Etiology. (PubMed, Vet Med Sci) - "Consequently, tolvaptan, a vasopressin receptor antagonist, was administered at 3 mg/kg PO daily, and water restriction was eased...In veterinary medicine, SIADH associated with brain diseases is often assumed to be attributed to hypothalamic-pituitary axis dysfunction, though inflammatory conditions can also cause hyponatremia. This report presents a case of SIADH accompanied by MUE, highlighting the role of inflammation as a cause of SIADH in dogs."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Inflammation • Ventriculomegaly

Tolvaptan in Autosomal Dominant Polycystic Kidney Disease (ADPKD): a multicenter real life Italian experience. (PubMed, Clin Kidney J) - "This real-life study confirms the feasibility, safety, and tolerability of tolvaptan treatment. In order to overcome the challenges of tolvaptan treatment, our experience suggests that a dedicated PKD team may play a key role in implementing strategies focused to reduce drop-out and achieve treatment success."

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

Decoding Hyponatremia: A Systematic Review of Diagnostic Pathways and Therapeutic Approaches Applied When Correction Fails. (PubMed, Cureus) - "Tolvaptan consistently improved serum sodium concentrations in patients with SIADH and heart failure, though its use was limited by high cost and the potential for overly rapid correction...When standard correction measures fail, clinicians should reassess the underlying etiology and escalate treatment accordingly. Vaptans offer rapid correction, urea ensures safe long-term management, and demeclocycline serves as a last-line therapeutic option."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology

Clinical trial on the pharmacokinetics, pharmacodynamics and safety of tolvaptan in healthy Chinese males: an open-label, single and multiple dosage, parallel group study. (PubMed, Front Pharmacol) - P1 | "Similar PK profiles were observed between single and multiple doses with slight accumulation. https://clinicaltrials.gov/, identifier NCT07166796, NCT07166783 and NCT07166887."

Clinical • Journal • PK/PD data • Xerostomia

THE NEED FOR NOVEL THERAPEUTIC DIRECTIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENT CARE. (PubMed, Clin J Am Soc Nephrol) - "At present, the only drugs approved to slow disease progression are the vasopressin V2-receptor antagonist tolvaptan and, in Italy, the somatostatin analogue octreotide long-acting release for the subset of patients with stage 4 chronic kidney disease...These include not only repurposed pharmacological agents, namely sodium-glucose cotransporter-2 inhibitors, metformin, and glucagon-like peptide-1 receptor agonists, but also innovative therapies, as it is the case for a monoclonal antibody against pregnancy-associated plasma protein-A, microRNA-17 inhibitors, and the polycystin-1 correcting agent VX-407. Dietary interventions, such as caloric restriction and ketogenic diets, are being tested in clinical trials as well, and could complement pharmacotherapy to slow disease progression. Moreover, the rapid advancements in the field of gene therapy for ADPKD suggest that this approach, though as yet only explored at experimental level, could be translated into clinical..."

Journal • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • MIR17 • PKD1

Real-world evidence for using urine osmolality as a practical tool in tolvaptan dose optimization in patients with ADPKD. (PubMed, Clin Nephrol) - "Urine osmolality is a practical and effective biomarker for guiding individualized tolvaptan titration in patients with ADPKD. This approach enabled adequate vasopressin suppression and was associated with a low discontinuation rate, supporting its use in real-world clinical practice."

HEOR • Journal • Real-world evidence • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Discovery of Non-benzoazacyclic V2R Antagonists for the Treatment of Autosomal Dominant Polycystic Kidney Disease. (PubMed, J Med Chem) - "In this study, structural analysis of V2R bound to the FDA-approved V2R antagonist tolvaptan and a previously reported derivative (compound 18) revealed that the interaction with a hydrophobic subpocket formed by residues V2065.39, I2095.42, and F2876.51 plays a critical role in antagonistic activity...In vitro and in vivo studies demonstrated that XYDC2050 effectively suppressed renal cyst formation and slowed disease progression. These results support XYDC2050 as a potential lead compound for ADPKD therapy."

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

Effectiveness of Salt Tablets in Inpatient Hyponatremia Improves with Higher Doses (KIDNEY WEEK 2025) - "For each case, we excluded treatment-days when NaCl tab administration occurred concomitantly or within +/- 24 hrs of additional treatment with either an IV NaCl-containing infusion/bolus (excluding drug vehicle) or oral tolvaptan, Na bicarbonate or Na phosphate...Results After excluding 47 patients due to concomitant therapy, 30 were included (mean age 72, 67% women, 90% white, mean baseline sNa 125 mEq/L)...High doses (i.e., 3 - 4 g tid/qid) were well tolerated, only 1 patient experienced mild nausea. Conclusion The effectiveness of NaCl tab for the treatment of inpatient hypoNa is greater when higher doses are used."

Clinical • Cardiovascular • Fibrosis • Heart Failure • Hepatology • Immunology

A Study of HRS-9057 in Patients With Heart Failure and Volume Overload (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Fujian Shengdi Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Oct 2025 | Trial primary completion date: Sep 2024 ➔ Oct 2025

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Tolvaptan versus other interventions for hyponatraemia in people with cirrhosis. (PubMed, Cochrane Database Syst Rev) - "This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of tolvaptan versus standard medical management, placebo, or other vaptans for the treatment of hyponatraemia in people with cirrhosis."

Journal • Fibrosis • Immunology

Kidney stones and autosomal dominant polycystic kidney disease: a state-of-the-art review. (PubMed, Ren Fail) - "Tolvaptan, a vasopressin V2 receptor antagonist, may have additional benefit by increasing urine volume, reducing supersaturation, and potentially mitigating stone risk. This review integrates nephrology, urology, and imaging perspectives to summarize the current understanding of nephrolithiasis in ADPKD, including its pathophysiology, clinical manifestations, diagnostic challenges, and management. We propose an ADPKD-specific diagnostic and management algorithm to optimize prevention, evaluation, and treatment of stone disease in this complex population."

Journal • Review • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Metabolic Disorders • Nephrology • Polycystic Kidney Disease • Renal Calculi • Renal Disease • Urolithiasis • Urology

Hyponatraemia and cancer. (PubMed, Best Pract Res Clin Endocrinol Metab) - "Interestingly, vasopressin receptor antagonists, mainly used for the treatment of hyponatraemia secondary to the syndrome of inappropriate antidiuresis and in polycystic kidney disease, effectively reduced cancer cell proliferation in in vitro and in vivo experiments. Although this needs to be confirmed on clinical grounds, it is tempting to hypothesize that vasopressin receptor antagonists might have a possible role in future anti-cancer strategies."

Journal • Review • Genetic Disorders • Nephrology • Oncology • Polycystic Kidney Disease • Renal Disease

Unmasking Liver Risks: Over-the-Counter Supplements Trigger Transient Hepatotoxicity in Patients with ADPKD on Tolvaptan (KIDNEY WEEK 2025) - "CYP3A4-mediated interactions with OTC supplements can cause transient hepatotoxicity in ADPKD patients on tolvaptan. Early detection and intervention allow for safe treatment interruption and rechallenge."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Genetic Disorders • Hepatology • Nephrology • Polycystic Kidney Disease • Renal Disease • CST3

Dual Molecular Diagnosis: COL4A3 and PKD1 (KIDNEY WEEK 2025) - "Over the next 5 years, despite intermittent RAASi use and avoidance of tolvaptan due to pregnancy desires, her renal function and albuminuria remained normal...Heterozygous COL4A3 mutations have wide phenotypic range and are poorly understood and classified. Increasing use of genetic sequencing will improve understanding of cystic-collagen diseases and their overlap."

Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Nephrology • Otorhinolaryngology • Polycystic Kidney Disease • Renal Disease • Rheumatology • PKD1 • PRKD1

Unmasking Late-Onset Autosomal Recessive PKD (KIDNEY WEEK 2025) - "The efficacy of tolvaptan to mitigate kidney disease progression in ARPKD is currently being evaluated...Rarely, ARPKD can present with symptoms confined to a single organ. Conclusion Late-onset ARPKD can present with a kidney-restricted disease phenotype and it should be considered in young adults with multiple kidney cysts and unexplained ESRD."

Cardiovascular • Chronic Kidney Disease • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Glomerulonephritis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Lupus Nephritis • Nephrology • Polycystic Kidney Disease • Portal Hypertension • Renal Disease • PKHD1

A Case Highlighting the Importance of Genetic Testing in Cystic Kidney Diseases (KIDNEY WEEK 2025) - "Previous MRI revealed class 1D cysts, though the patient declined tolvaptan treatment...Discussion Genetic testing, along with imaging, is essential for diagnosing cystic kidney diseases, supporting accurate diagnosis, management of renal and systemic involvement, and genetic counseling. MRI showing multiple cysts in bilateral kidneys"

Clinical • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • CNS Disorders • Epilepsy • Genetic Disorders • Infectious Disease • Nephrology • Polycystic Kidney Disease • Pulmonary Disease • Renal Disease • Solid Tumor • TSC2

Calculated Preemptive Strike: Solving Overcorrection of Hyponatremia with Math and Medicine (KIDNEY WEEK 2025) - "To limit the serum sodium rise to no more than 8 mEq over 24 hrs,the desired free water clearance was estimated at 2.6 lit/day.Anticipating an excessive free water loss of ~11.4 lit (13–2.6L),we preemptively initiated a D5W infusion at a rate of 500 mL/hr, prior to the serum sodium exceeding the 8 mEq/L threshold. With this approach,the serum sodium was safely corrected by 7 mEq/L over 24 hrs Discussion This case highlights a proactive strategy to prevent overcorrection of serum sodium following tolvaptan administration.By using urine osmolality and urine output to calculate free water clearance,we were able to predict the risk of overcorrection.Our approach demonstrates the value of leveraging free water clearance to guide proactive management,rather than reacting solely to changes in serum sodium levels, in order to prevent rapid correction of hyponatremia"

Cardiovascular • CNS Disorders • Epilepsy • Heart Failure

Short-Term Effects of an SGLT2 Inhibitor on Divalent Ions in Patients with ADPKD: The SIDIA Trial (KIDNEY WEEK 2025) - "Conclusion In ADPKD patients with and without tolvaptan, short-term empagliflozin was safe, showing no significant effects on urinary calcium, phosphate, or magnesium. Analyses used two-sided tests (α=0.05). GLMM, generalized linear mixed model."

Clinical • Late-breaking abstract • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Gout • Inflammation • Inflammatory Arthritis • Polycystic Kidney Disease • Rheumatology

Novel Neutralizing Monoclonal Antibody (mAb) Against Pregnancy-Associated Plasma Protein A (PAPPA) for the Treatment of ADPKD (KIDNEY WEEK 2025) - "Tolvaptan is the sole medicine approved for ADPKD but has aquaresis side effects and risk of liver injury...These data support the further exploration of PAPPA inhibition as a therapeutic approach for the treatment of ADPKD. Figure 1: Reduction of tKV growth in JCK mice after PAPPA mAb treatments"

Autosomal Dominant Polycystic Kidney Disease • Hepatology • Liver Failure • Polycystic Kidney Disease • Renal Disease • IGF1 • IGFBP2

Severe Hyponatremia in Acute Myeloid Leukemia: A Rare Manifestation of Cytarabine-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) (KIDNEY WEEK 2025) - "He received Cytarabine and Idarubicin as 7+3 regimen...He was then given tolvaptan 7.5 mg...Patient developed hyponatremia after day 2 of Cytarabine infusion. His sodium level normalized after he finished Cytarabine infusion and did not require any treatment to maintain his sodium level."

Acute Myelogenous Leukemia • Heart Failure • Hematological Malignancies • Leukemia

Urine Osmolality for Individualized Dosing of Tolvaptan in Adults with Rapidly Progressive ADPKD (KIDNEY WEEK 2025) - "Conclusion In this prospective study of adult patients with ADPKD, we found that using a urine osmolality of less than 200 mOsm/kg to titrate tolvaptan therapy results in lower tolvaptan doses, a very low discontinuation rate, and fewer side effects. We believe that urine osmolality, an indicator of vasopressin-2 receptor suppression, could help individualize tolvaptan dosing in clinical practice."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Nephrology • Polycystic Kidney Disease

Uric Acid Microcrystal Injury as a Driver of CKD and PKD (KIDNEY WEEK 2025) - P, P=N/A | "Methods We analyzed clinical data from two ADPKD studies (NCT02497521, NCT04680780), excluding patients on tolvaptan...Reducing UA formation, and urine alkalization with citrate may be disease-modifying in CKD and ADPKD. NLR or pyuria may serve as biomarkers of progression."

Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Chronic Kidney Disease • Diabetes • Hypertension • Inflammation • Polycystic Kidney Disease • CXCL8 • IL12A

Three-Month Interim Analysis of Ketogenic Metabolic Therapy in Japanese Patients with ADPKD (KIDNEY WEEK 2025) - "Methods This study enrolled adult ADPKD patients who had not previously received tolvaptan treatment...Tolerability was high, no participants discontinued or interrupted the ketogenic diet during the three-month study period. Conclusion Although these are preliminary results, our findings indicate that even among Japanese ADPKD patients the intervention was well tolerated and may offer therapeutic benefits, particularly in reducing kidney volume."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Polycystic Kidney Disease

Real-Time Platform for Data Analysis and Visualization in ADPKD: Insights from a Large Prospective Cohort Study (KIDNEY WEEK 2025) - P | "Conclusion MEDA is a powerful tool to characterize the natural disease course of ADPKD in a real-time fashion. It will, thus, also be a crucial basis to patient stratification for clinical trials, detection of novel indicators of disease progression and the examination of the impact of therapeutic interventions as exemplified by the analysis on the effect of tolvaptan."

Clinical • Autosomal Dominant Polycystic Kidney Disease • Polycystic Kidney Disease • Renal Disease