ArticleJournal of the American Society of Nephrology : JASN2015
Tolvaptan plus pasireotide shows enhanced efficacy in a PKD1 model.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease.Kidney international · 2019Trial
- Trial
- Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2018Trial
- Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial.Clinical journal of the American Society of Nephrology : CJASN · 2016Trial
- Review
- The Ion channel, CFTR, assembles with HIPPO pathway proteins TAZ and YAP in polycystic kidney disease.The Journal of biological chemistry · 2026Article
- Kidney Volume and Molecular Processes are Dynamic in ADPKD.Kidney international reports · 2026Article
- Inactivation of Pkd2 in adult mice results in delayed cyst formation and identifies sex as a major modifier of disease severity.Kidney international · 2026Article
- Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.Purinergic signalling · 2026Article
- Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease.PLoS genetics · 2025Article
- Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models.JCI insight · 2025Article
- Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.Biomedicines · 2025Review
- AAV1-CFTR preferentially transduces cysts and reduces cyst size in a mouse model of ADPKD.American journal of physiology. Cell physiology · 2025Article
- Ciliary G-Protein Coupled Receptor Signaling in Polycystic Kidney Disease.International journal of molecular sciences · 2025Review
- Cyclic Adenosine Monophosphate Signaling in Chronic Kidney Disease: Molecular Targets and Therapeutic Potentials.International journal of molecular sciences · 2024Review
- Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models.American journal of physiology. Renal physiology · 2024Article
- Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease.Cell stem cell · 2024Article
- Inhibiting centrosome clustering reduces cystogenesis and improves kidney function in autosomal dominant polycystic kidney disease.JCI insight · 2024Article
- CFTR and PC2, partners in the primary cilia in autosomal dominant polycystic kidney disease.American journal of physiology. Cell physiology · 2023Article
- Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of ESRD. A central defect associated with ADPKD pathology is elevated levels of 3', 5'-cyclic AMP (cAMP). Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression. Here, we tested the efficacy of these compounds individually and in combination in a hypomorphic PKD1 model, Pkd1(R3277C/R3277C) (Pkd1(RC/RC)), in a 5-month preclinical trial. Initially, the Pkd1(RC/RC) model was inbred into the C57BL/6 background, minimizing disease variability, and the pathogenic effect of elevating cAMP was confirmed by treatment with the AC6 stimulant desmopressin. Treatment with tolvaptan or pasireotide alone markedly reduced cyst progression and in combination showed a clear additive effect. Furthermore, combination treatment significantly reduced cystic and fibrotic volume and decreased cAMP to wild-type levels. We also showed that Pkd1(RC/RC) mice experience hepatic hypertrophy that can be corrected by pasireotide. The observed additive effect reinforces the central role of AC6 and cAMP in ADPKD pathogenesis and highlights the likely benefit of combination therapy for patients with ADPKD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.