REVIEW PAPER
The impact of tolvaptan on autosomal dominant polycystic kidney disease – literature review
1
Department of Forensic Medicine, Pomeranian Medical University, Szczecin, Poland
2
Clinical Department of General Surgery, Pomeranian Medical University, Szczecin, Poland
3
Clinic of Nephrology, Transplantology and Internal Diseases, University Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, Poland
Submission date: 2024-04-29
Final revision date: 2024-09-11
Acceptance date: 2024-11-27
Publication date: 2025-12-15
Corresponding author
Krzysztof Kowalik
Krzysztof Kowalik MD, PhD Clinical Department of General Surgery Pomeranian Medical University Szczecin, Poland
Krzysztof Kowalik MD, PhD Clinical Department of General Surgery Pomeranian Medical University Szczecin, Poland
Medical Studies 2025;41(4):322-329
KEYWORDS
olycystic kidney diseaseautosomal dominant inheritancetolvaptantreatmentautosomal dominant polycystic kidney disease
TOPICS
ABSTRACT
This article presents current data from international literature on the impact of tolvaptan on autosomal dominant polycystic kidney disease (ADPKD). The authors have reviewed the latest clinical research literature. Additionally, the paper discusses the molecular biology of ADPKD and the effects of tolvaptan use on liver and kidney function, and presents the treatment of the described disease in adults and children. Complications of tolvaptan treatment are also briefly discussed.
REFERENCES (60)
1.
Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJM, Torres VE. Polycystic kidney disease. Nat Rev Dis Primers. 2018; 4(1): 50.
2.
Harris PC, Torres VE. Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest. 2014; 124(6): 2315-2324.
3.
De Rechter S, Bockenhauer D, Guay-Woodford LM, Liu I, Mallett AJ, Soliman NA, Sylvestre LC, Schaefer F, Lie- bau MC, Mekahli D; ADPedKD Consortium. ADPedKD: a global online platform on the management of children with ADPKD. Kidney Int Rep. 2019; 4(9): 1271-1284.
4.
Gimpel C, Bergmann C, Bockenhauer D, Breysem L, Cadnapaphornchai MA, Cetiner M, Dudley J, Emma F, Konrad M, Harris T, Harris PC, König J, Liebau MC, Marlais M, Mekahli D, Metcalfe AM, Oh J, Perrone RD, Sinha MD, Titieni A, Torra R, Weber S, Winyard PJD, Schaefer F. International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people. Nat Rev Nephrol. 2019; 15(11): 713-726.
5.
Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, Pei Y, Perro- ne RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC; Conference Participants. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015; 88(1): 17-27.
6.
Ong AC, Devuyst O, Knebelmann B, Walz G; ERA-EDTA Working Group for Inherited Kidney Diseases. Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet. 2015; 385(9981): 1993-2002. Erratum in: Lancet. 2015; 385(9987): 2576.
7.
Porath B, Gainullin VG, Cornec-Le Gall E, Dillinger EK, Heyer CM, Hopp K, Edwards ME, Madsen CD, Mauritz SR, Banks CJ, Baheti S, Reddy B, Herrero JI, Bañales JM, Hogan MC, Tasic V, Watnick TJ, Chapman AB, Vigneau C, Lavainne F, Audrézet MP, Ferec C, Le Meur Y, Torres VE; Genkyst Study Group, HALT Progression of Polycystic Kidney Disease Group; Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease; Harris PC. Mutations in GANAB, encoding the glucosidase II subunit, cause autosomal-dominant polycystic kidney and liver disease. Am J Hum Genet. 2016; 98(6): 1193-1207.
8.
Cornec-Le Gall E, Olson RJ, Besse W, Heyer CM, Gainullin VG, Smith JM, Audrézet MP, Hopp K, Porath B, Shi B, Baheti S, Senum SR, Arroyo J, Madsen CD, Férec C, Joly D, Jouret F, Fikri-Benbrahim O, Charasse C, Coulibaly JM, Yu AS, Khalili K, Pei Y, Somlo S, Le Meur Y, Torres VE; Genkyst Study Group; HALT Progression of Polycystic Kidney Disease Group; Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease; Harris PC. Monoallelic mutations to DNAJB11 cause atypical autosomal-dominant polycystic kidney disease. Am J Hum Genet. 2018; 102(5): 832-844.
9.
Reed BY, McFann K, Bekheirnia MR, Nobakhthaghighi N, Masoumi A, Johnson AM, Shamshirsaz AA, Kelleher CL, Schrier RW. Variation in age at ESRD in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2008; 51(2): 173-183.
10.
Torres VE, Harris PC. Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol. 2014; 25(1): 18-32.
11.
Patel V, Li L, Cobo-Stark P, Shao X, Somlo S, Lin F, Igara- shi P. Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum Mol Genet. 2008; 17(11): 1578-1590.
12.
Fujiki T, Ando F, Murakami K, Isobe K, Mori T, Susa K, Nomura N, Sohara E, Rai T, Uchida S. Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation. Sci Rep. 2019; 9(1): 9245.
13.
Baur BP, Meaney CJ. Review of tolvaptan for autosomal dominant polycystic kidney disease. Pharmacotherapy. 2014; 34(6): 605-616.
14.
Lu J, Xu W, Gong L, Xu M, Tang W, Jiang W, Xie F, Ding L, Qian X. Efficacy and safety of tolvaptan versus placebo in the treatment of patients with autosomal dominant polycystic kidney disease: a meta-analysis. Int Urol Nephrol. 2023; 55(3): 631-640.
15.
Torres VE, Higashihara E, Devuyst O, Chapman AB, Gansevoort RT, Grantham JJ, Perrone RD, Ouyang J, Blais JD, Czerwiec FS; TEMPO 3:4 Trial Investigators. Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage: results from the TEMPO 3:4 trial. Clin J Am Soc Nephrol. 2016; 11(5): 803-811.
16.
Perrone RD, Chapman AB, Oberdhan D, Czerwiec FS, Sergeyeva O, Ouyang J, Shoaf SE. The NOCTURNE randomized trial comparing 2 tolvaptan formulations. Kidney Int Rep. 2020; 5(6): 801-812. Erratum in: Kidney Int Rep. 2020; 5(12): 2407-2408.
17.
Kramers BJ, van Gastel MDA, Boertien WE, Meijer E, Gansevoort RT. Determinants of urine volume in ADPKD patients using the vasopressin V2 receptor antagonist tolvaptan. Am J Kidney Dis. 2019; 73(3): 354-362.
18.
Geertsema P, Koorevaar IW, Ipema KJR, Kramers BJ, Casteleijn NF, Gansevoort RT, Meijer E. Effects of salt and protein intake on polyuria in V2RA-treated ADPKD patients. Nephrol Dial Transplant. 2024; 39(4): 707-716.
19.
Meijer E, Gansevoort RT, de Jong PE, van der Wal AM, Leonhard WN, de Krey SR, van den Born J, Mulder GM, van Goor H, Struck J, de Heer E, Peters DJM. Therapeutic potential of vasopressin V2 receptor antagonist in a mouse model for autosomal dominant polycystic kidney disease: optimal timing and dosing of the drug. Nephrol Dial Transplant. 2011; 26(8): 2445-2453.
20.
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, Ouyang J, McQuade RD, Blais JD, Czerwiec FS, Sergeyeva O; REPRISE Trial Investigators. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med. 2017; 377(20): 1930-1942.
21.
Miyazaki T, Fujiki H, Yamamura Y, Nakamura S, Mori T. Tolvaptan, an orally active vasopressin V(2)-receptor antagonist - pharmacology and clinical trials. Cardiovasc Drug Rev. 2007; 25(1): 1-13.
22.
Pezzuoli C, Biagini G, Magistroni R. Ketogenic interventions in autosomal dominant polycystic kidney disease: a comprehensive review of current evidence. Nutrients. 2024; 16(16): 2676.
23.
Steele CN, Nowak KL. Nonpharmacological management of autosomal dominant polycystic kidney disease. Adv Kidney Dis Health. 2023; 30(3): 220-227.
24.
Choi HY, Park HC, Ha SK. High water intake and progression of chronic kidney diseases. Electrolyte Blood Press. 2015; 13(2): 46-51.
25.
Zhou X, Torres VE. Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling. Front Mol Biosci. 2022; 9: 981963.
26.
Yheskel M, Lakhia R, Cobo-Stark P, Flaten A, Patel V. Anti-microRNA screen uncovers miR-17 family within miR-17~92 cluster as the primary driver of kidney cyst growth. Sci Rep. 2019; 9(1): 1920.
27.
Ramalingam H, Yheskel M, Patel V. Modulation of polycystic kidney disease by non-coding RNAs. Cell Signal. 2020; 71: 109548.
28.
Hajirezaei F, Ghaderian SMH, Hasanzad M, Nafar M, Ghadiani MH, Biglari S, Sohrabifar N, Jafari H. Methylation of the PKD1 promoter inversely correlates with its expression in autosomal dominant polycystic kidney disease. Rep Biochem Mol Biol. 2020; 9(2): 193-198.
29.
Bowden SA, Rodger EJ, Bates M, Chatterjee A, Eccles MR, Stayner C. Genome-scale single nucleotide resolution analysis of DNA methylation in human autosomal dominant polycystic kidney disease. Am J Nephrol. 2018; 48(6): 415-424.
30.
Woo YM, Bae JB, Oh YH, Lee YG, Lee MJ, Park EY, Choi JK, Lee S, Shin Y, Lyu J, Jung HY, Lee YS, Hwang YH, Kim YJ, Park JH. Genome-wide methylation profiling of ADPKD identified epigenetically regulated genes associated with renal cyst development. Hum Genet. 2014; 133(3): 281-297.
31.
Kurbegovic A, Pacis RC, Trudel M. Modeling Pkd1 gene-targeted strategies for correction of polycystic kidney disease. Mol Ther Methods Clin Dev. 2023; 29: 366-380.
32.
King BF, Reed JE, Bergstralh EJ, Sheedy PF 2nd, Torres VE. Quantification and longitudinal trends of kidney, renal cyst, and renal parenchyma volumes in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2000; 11(8): 1505-1511.
33.
Messchendorp AL, Spithoven EM, Casteleijn NF, Dam WA, van den Born J, Tonnis WF, Gaillard CAJM, Meijer E; DIPAK Consortium. Association of plasma somatostatin with disease severity and progression in patients with autosomal dominant polycystic kidney disease. BMC Nephrol. 2018; 19(1): 368.
34.
Arjune S, Späth MR, Oehm S, Todorova P, Schunk SJ, Lettenmeier K, Chon SH, Bartram MP, Antczak P, Grundmann F, Fliser D, Müller RU. DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease. Clin Kidney J. 2023; 17(1): sfad262.
35.
Watkins PB, Lewis JH, Kaplowitz N, Alpers DH, Blais JD, Smotzer DM, Krasa H, Ouyang J, Torres VE, Czerwiec FS, Zimmer CA. Clinical pattern of tolvaptan-associated liver injury in subjects with autosomal dominant polycystic kidney disease: analysis of clinical trials database. Drug Saf. 2015; 38(11): 1103-1113.
36.
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Dandurand A, Ouyang J, Czerwiec FS, Blais JD, the TEMPO 4:4 Trial Investigators. Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrol Dial Transplant. 2017; 32(7): 1262.
37.
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Lee J, Hoke ME, Estilo A, Sergeyeva O. Multicenter study of long-term safety of tolvaptan in later-stage autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2020; 16(1): 48-58.
38.
Bellos I. Safety profile of tolvaptan in the treatment of autosomal dominant polycystic kidney disease. Ther Clin Risk Manag. 2021; 17: 649-656.
39.
Mosedale M, Watkins PB. Drug-induced liver injury: advances in mechanistic understanding that will inform risk management. Clin Pharmacol Ther. 2017; 101(4): 469-480.
40.
Levey AS, Eckardt KU, Dorman NM, Christiansen SL, Hoorn EJ, Ingelfinger JR, Inker LA, Levin A, Mehrotra R, Palevsky PM, Perazella MA, Tong A, Allison SJ, Bockenhauer D, Briggs JP, Bromberg JS, Davenport A, Fel- dman HI, Fouque D, Gansevoort RT, Gill JS, Greene EL, Hemmelgarn BR, Kretzler M, Lambie M, Lane PH, Laycock J, Leventhal SE, Mittelman M, Morrissey P, Ostermann M, Rees L, Ronco P, Schaefer F, St Clair Russell J, Vinck C, Walsh SB, Weiner DE, Cheung M, Jadoul M, Winkel- mayer WC. Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int. 2020; 97(6): 1117-1129.
41.
Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012; 367(25): 2407-2418.
42.
Edwards ME, Chebib FT, Irazabal MV, Ofstie TG, Bun- gum LA, Metzger AJ, Senum SR, Hogan MC, El-Zoghby ZM, Kline TL, Harris PC, Czerwiec FS, Torres VE. Long-term administration of tolvaptan in autosomal dominant polycystic kidney disease [published correction appears in Clin J Am Soc Nephrol. 2019; 14(6): 910]. Clin J Am Soc Nephrol. 2018; 13(8): 1153-1161.
43.
Torres VE, Gansevoort RT, Perrone RD, Chapman AB, Ouyang J, Lee J, Japes H, Nourbakhsh A, Wang T. Tolvaptan in ADPKD patients with very low kidney function. Kidney Int Rep. 2021; 6(8): 2171-2178.
44.
Torres VE, Erickson SB, Smith LH, Wilson DM, Hattery RR, Segura JW. The association of nephrolithiasis and autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1988; 11(4): 318-325.
45.
Nishiura JL, Neves RF, Eloi SR, Cintra SM, Ajzen SA, Heilberg IP. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol. 2009; 4(4): 838-844.
46.
Cheungpasitporn W, Rossetti S, Friend K, Erickson SB, Lieske JC. Treatment effect, adherence, and safety of high fluid intake for the prevention of incident and recurrent kidney stones: a systematic review and meta-analysis. J Nephrol. 2016; 29(2): 211-219.
47.
Cheungpasitporn W, Erickson SB, Rule AD, Enders F, Lieske JC. Short-term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate and uric acid supersaturations. J Urol. 2016; 195(5): 1476-1481.
48.
Bargagli M, Dhayat NA, Anderegg M, Semmo M, Huynh-Do U, Vogt B, Ferraro PM, Fuster DG. Urinary lithogenic risk profile in ADPKD patients treated with tolvaptan. Clin J Am Soc Nephrol. 2020; 15(7): 1007-1014.
49.
Casteleijn NF, Blais JD, Chapman AB, Czerwiec FS, Devuyst O, Higashihara E, Leliveld AM, Ouyang J, Perro- ne RD, Torres VE, Gansevoort RT; TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3:4 Trial Investigators. Tolvaptan and kidney pain in patients with autosomal dominant polycystic kidney disease: secondary analysis from a randomized controlled trial. Am J Kidney Dis. 2017; 69(2): 210-219.
50.
Nowak KL, Cadnapaphornchai MA, Chonchol MB, Schrier RW, Gitomer B. Long-term outcomes in patients with very-early onset autosomal dominant polycystic kidney disease. Am J Nephrol. 2016; 44(3): 171-178.
51.
Grantham JJ. Rationale for early treatment of polycystic kidney disease. Pediatr Nephrol. 2015; 30(7): 1053-1062.
52.
Cadnapaphornchai MA. Autosomal dominant polycystic kidney disease in children. Curr Opin Pediatr. 2015; 27(2): 193-200.
53.
Mekahli D, Guay-Woodford LM, Cadnapaphornchai MA, Greenbaum LA, Litwin M, Seeman T, Dandurand A, Shi L, Sikes K, Shoaf SE, Schaefer F. Tolvaptan for children and adolescents with autosomal dominant polycystic kidney disease: randomized controlled trial. Clin J Am Soc Nephrol. 2023; 18(1): 36-46.
54.
Wang X, Constans MM, Chebib FT, Torres VE, Pellegrini L. Effect of a vasopressin V2 receptor antagonist on polycystic kidney disease development in a rat model. Am J Nephrol. 2019; 49(6): 487-493.
55.
Woodhead JL, Pellegrini L, Shoda LKM, Howell BA. Comparison of the hepatotoxic potential of two treatments for autosomal-dominant polycystic kidney diseaseusing quantitative systems toxicology modeling. Pharm Res. 2020; 37(2): 24.
56.
Capuano I, Buonanno P, Riccio E, Rizzo M, Pisani A. Tolvaptan vs. somatostatin in the treatment of ADPKD: a review of the literature. Clin Nephrol. 2022; 97(3): 131-140.
57.
Messchendorp AL, Casteleijn NF, Meijer E, Gansevoort RT. Somatostatin in renal physiology and autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2020; 35(8): 1306-1316.
58.
Perico N, Ruggenenti P, Perna A, Caroli A, Trillini M, Siro- ni S, Pisani A, Riccio E, Imbriaco M, Dugo M, Morana G, Granata A, Figuera M, Gaspari F, Carrara F, Rubis N, Villa A, Gamba S, Prandini S, Cortinovis M, Remuzzi A, Remuzzi G; ALADIN 2 Study Group. Octreotide-LAR in later-stage autosomal dominant polycystic kidney disease (ALADIN 2): a randomized, double-blind, placebo-controlled, multicenter trial. PLoS Med. 2019; 16(4): e1002777.
59.
Seliger SL, Watnick T, Althouse AD, Perrone RD, Abebe KZ, Hallows KR, Miskulin DC, Bae KT. Baseline characteristics and patient-reported outcomes of ADPKD patients in the multicenter TAME-PKD clinical trial. Kidney360. 2020; 1(12): 1363-1372.
60.
Zhang J, Chen J, Xu J, Xue C, Mao Z. Plant-derived compounds for treating autosomal dominant polycystic kidney disease. Front Nephrol. 2023; 3: 1071441.
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