Tolvaptan no tratamento da Doença Renal Policística Autossômica Dominante (DRPAD): Eficácia e efeitos na qualidade de vida
DOI:
https://doi.org/10.33448/rsd-v14i5.48812Palavras-chave:
Tolvaptan; Rim Policístico Autossômico Dominante; Eficácia; Qualidade de Vida.Resumo
A DRPAD causa cistos renais, aumentando o volume renal total (VRT) e levando à insuficiência renal crônica (IRC), com declínio da taxa de filtração glomerular (TFG). Mutações nos genes das policistinas alteram o influxo de cálcio e a produção de AMPc, formando cistos sob influência da vasopressina. Tolvaptan, um inibidor do receptor de vasopressina, visa retardar o declínio da função renal e melhorar a qualidade de vida. O objetivo desta revisão é demonstrar os efeitos do Tolvaptan na DRPAD, destacando sua eficácia e impacto na qualidade de vida e na progressão para IRC. Utilizou-se as bases de dados BVS, PubMed e New England Journal of Medicine, obtendo 446 resultados, dos quais 41 restaram após a triagem manual pelo Excel, incluídos ensaios clínicos, análises retrospectivas e coortes, sem restrição de idioma. Os resultados demonstraram que o Tolvaptan reduziu a proliferação de cistos, limitou a expansão do VRT em 2,6%, retardou a queda da TFG em até 10 ml/min/1,73 m² em 3 anos e prolongou a progressão para IRC em quase 8,5 anos. Efeitos colaterais incluíram aumento de até 138% no volume urinário, aumento de enzimas hepáticas e creatinoquinase. O monitoramento mensal nos primeiros 18 meses é crucial e a suspensão temporária reverte efeitos indesejados em casos de descompensação hepática. Logo, o medicamento mostra ser eficaz no tratamento da DRPAD, com prolongamento importante da vida renal. Apesar dos efeitos colaterais, o medicamento é seguro e eficaz, se monitorado adequadamente.
Referências
Akihisa, T., Kataoka, H., Makabe, S., Manabe, S., Yoshida, R., Ushio, Y. et al. (2022). Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease. Clinical and Experimental Nephrology. 26(6), 540-51.
Akihisa, T., Manabe, S., Kataoka, H., Makabe, S., Yoshida, R., Ushio, Y. et al. (2021). Dose-dependent effect of tolvaptan on renal prognosis in patients with autosomal dominant polycystic kidney disease. Kidney360. 2(7), 1148-51.
Alpers, D. H., Lewis, J. H., Hunt, C. M., Freston, J. W., Torres, V. E., Li, H. et al. (2023). Clinical pattern of tolvaptan-associated liver injury in trial participants with autosomal dominant polycystic kidney disease (ADPKD): an analysis of pivotal clinical trials. American Journal of Kidney Diseases. 81(3), 281-93. e1.
Anderegg, M. A., Dhayat, N. A., Sommer, G., Semmo, M., Huynh-Do, U., Vogt, B. et al. (2020). Quality of life in autosomal dominant polycystic kidney disease patients treated with tolvaptan. Kidney medicine. 2(2), 162-71.
Borrego Utiel, F. J. & Merino García, E. (2021). Glomerular filtration rate is the main predictor of urine volume in autosomal dominant polycystic kidney disease patients treated with tolvaptan when daily osmolar excretion is expressed as urinary osmolality/creatinine ratio. Clinical Kidney Journal. 14 (3), 1031-3. https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-019-1290-5.
Chebib, F.T., Perrone, R. D., Chapman, A. B., Dahl, N. K., Harris, P. C., Mrug, M. et al. (2018). A practical guide for treatment of rapidly progressive ADPKD with tolvaptan. Journal of the American Society of Nephrology. 29(10), 2458-70.
Chebib, F.T., Zhou, X., Garbinsky, D., Davenport, E., Nunna, S., Oberdhan, D. et al. (2023). Tolvaptan and kidney function decline in older individuals with autosomal dominant polycystic kidney disease: a pooled analysis of randomized clinical trials and observational studies. Kidney Medicine. 5(6), 100639.
Crossetti, M. G. M. (2012). Revisión integradora de la investigación en enfermería el rigor científico que se le exige. Maria Da Graça Oliveira Crossetti. Rev. Gaúcha Enferm.33(2),8-9.
Edwards, M. E., Chebib, F. T., Irazabal, M. V., Ofstie, T. G., Bungum, L. A., Metzger, A. J. et al. (2018). Long-term administration of tolvaptan in autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology. 13(8), 1153-61.
Estilo, A., Tracy, L., Matthews, C., Riggen, M., Stemhagen, A., Wilt, T. et al. Evaluating the impact of a Risk Evaluation and Mitigation Strategy with tolvaptan to monitor liver safety in patients with autosomal dominant polycystic kidney disease. Clinical kidney journal. 15(8), 1553-61.
Gil, A. C. (2017). Como elaborar projetos de pesquisa. (6ed.). Editora Atlas.
Atlas Gkekas, E., Tang, T. Y. T., Green, A., Davidson, H., Fraser, R., Sayer, J. A. et al. (2022). Outcomes from the Northeast England cohort of autosomal dominant polycystic kidney disease (ADPKD) patients on tolvaptan. Frontiers in Nephrology. 2, 984165. doi: https://doi.org/10.3389/fneph.2022.984165;
Guerra-Torres, X. E., Esparragoza, J. P., Fernandez, M. P., Rodríguez, M. F., Ramos, J. M., Miguel, P. M. et al. (2020). Safety and Tolerability of Tolvaptan in an Autosomal Dominant Polycystic Kidney Disease Spanish Cohort: A Real-World Experience. Cureus. 12(9), e10207. doi: 10.7759/cureus.10207.
Higashihara, E., Horie, S., Muto, S., Kawano, H., Tambo, M., Yamaguchi, T. et al. (2020). Imaging identification of rapidly progressing autosomal dominant polycystic kidney disease: simple eligibility criterion for tolvaptan. American Journal of Nephrology. 51(11), 881-90.
Huh, H., Kim, Y. S., Chung, W., Kim, Y. L., Kim, Y., Han, S. et al. (2023). Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period. Kidney Research and Clinical Practice. 42(2), 216.
Kramers, B. J., van Gastel, M. D., Boertien, W. E., Meijer, E. & Gansevoort, R. T. (2019). Determinants of urine volume in ADPKD patients using the vasopressin V2 receptor antagonist tolvaptan. American Journal of Kidney Diseases. 73(3), 354-62.
Mader, G., Mladsi, D., Sanon, M., Purser, M., Barnett, C. L., Oberdhan, D. et al. (2022). A disease progression model estimating the benefit of tolvaptan on time to end-stage renal disease for patients with rapidly progressing autosomal dominant polycystic kidney disease. BMC nephrology. 23(1), 334.
Makabe, S., Manabe, S., Kataoka, H., Akihisa, T., Yoshida, R., Ushio, Y. et al. (2021). Urinary aquaporin 2 as a potential indicator predicting tolvaptan response in patients with ADPKD. Kidney International Reports. 6(9), 2436-44.
Masuda, H., Shimizu, N., Sekine, K., Okato, A., Hou, K., Suyama, T. et al. (2023). Efficacy and safety of tolvaptan for patients with autosomal dominant polycystic kidney disease in real-world practice: A Single Institution Retrospective Study. in vivo. 37(2), 801-5.
Mattos, P. C. (2015). Tipos de revisão de literatura. Unesp, 1-9. Recuperado de https://www.fca.unesp.br/Home/Biblioteca/tipos-de-evisao-de-literatura.pdf.
Mekahli, D., Guay-Woodford, L. M., Cadnapaphornchai, M. A., Goldstein, S. L., Dandurand, A., Jiang, H. et al. (2024). Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan. Pediatric Nephrology. 39(5),1481-90.
Mekahli, D., Guay-Woodford, L. M., Cadnapaphornchai, M. A., Greenbaum, L. A., Litwin, M., Seeman, T. et al. (2023). Tolvaptan for children and adolescents with autosomal dominant polycystic kidney disease: randomized controlled trial. Clinical Journal of the American Society of Nephrology. 18(1), 36-46.
Mochizuki, T., Muto, S., Miyake, M., Tanaka, T. & Wang, W. (2021). Safety and efficacy of Tolvaptan in real-world patients with autosomal dominant polycystic kidney disease-interim results of SLOW-PKD surveillance. Clinical and Experimental Nephrology. 25(11), 1231-9. doi: 10.1007/s10157-021-02100-0.
Moriyama, T., Nakayama, Y., Soejima, M., Yokota, Y., Ota, K., Ito, S. et al. (2020). Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations. Clinical and Experimental Nephrology. 25(3), 251–60. doi: 10.1007/s10157-020-01988-4.
Müller, R-U, Messchendorp, A. L., Birn, H., Capasso, G., Cornec-Le Gall, E., Devuyst, O. et al. (2022). An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International. Nephrology Dialysis Transplantation. 37(5), 825-39.
Naranjo, J., Borrego, F., Rocha, J. L., Salgueira, M., Martín-Gomez, M. A., Orellana, C. et al. (2022). Real clinical experience after one year of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease. Frontiers in Medicine. 29(9), 987092. doi: 10.3389/fmed.2022.987092. eCollection 2022.
Pei, Y. & Watnick, P. (2024). Autosomal dominant polycystic kidney disease (ADPKD): Genetics of the disease and mechanisms of cyst growth. Uptodate. https://www.uptodate.com/contents/autosomal-dominant-polycystic-kidney-disease-adpkd-genetics-of-the-disease-and-mechanisms-of-cyst-growth.
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Editora UAB/NTE/UFSM.
Raby, K. L., Horsely, H., McCarthy-Boxer, A., Norman, J. T. & Wilson, P. D. (2021). Urinary exosome proteomic profiling defines stage-specific rapid progression of autosomal dominant polycystic kidney disease and tolvaptan efficacy. BBA advances. 13(1), 100013. doi: 10.1016/j.bbadva.2021.100013. eCollection 2021.
Rodríguez-Espinosa, D., Broseta, J. J., Bastida, C., Álvarez-Mora, M. I., Nicolau, C., Alvarez, C. et al. (2023). Creatine kinase elevation in autosomal dominant polycystic kidney disease patients on tolvaptan treatment. Nephron. 147(3-4), 152-7.
Saito, R., Yamamoto, H., Ichihara, N., Kumamaru, H., Nishimura, S., Shimada, K. et al. (2022). Persistence of tolvaptan medication for autosomal dominant polycystic kidney disease: A retrospective cohort study using Shizuoka Kokuho Database. Medicine. 101(40), e30923.
Schaefer, F., Mekahli, D., Emma, F., Gilbert, R. D., Bockenhauer, D., Cadnapaphornchai, M. A. et al. (2019). Tolvaptan use in children and adolescents with autosomal dominant polycystic kidney disease: rationale and design of a two-part, randomized, double-blind, placebo-controlled trial. European Journal of Pediatrics. 178, 1013-21.
Schirutschke, H., Gross, P., Paliege, A. & Hugo, C. (2021). 10-Year Evaluation of Adherence and Satisfaction with Information about Tolvaptan in ADPKD: A Single-Center Pilot Study. Patient preference and adherence. 4(15), 1941-52. doi: 10.2147/PPA.S325738. eCollection 2021.
Sekine, A., Hoshino, J., Fujimaru, T., Suwabe, T., Mizuno, H., Kawada, M. et al. (2020). Genetics may predict effectiveness of tolvaptan in autosomal dominant polycystic kidney disease. American Journal of Nephrology. 51(9), 745-51.
Shimoda, N., Ikeda, M., Yan, T., Kawasaki, S., Hirama, A., Kashiwagi, T. et al. (2022). Long-term benefits of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease. Journal of Nippon Medical School. 89(3), 287-94.
Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of business research, 104, 333-339.
Thomas, M., Gois, P. H. F., Butcher, B. E., Ta, M. H. & Van Wyk, G. W. (2021). Treatment persistence to tolvaptan in patients with autosomal dominant polycystic kidney disease: a secondary use of data analysis of patients in the IMADJIN® dataset. BMC nephrology. 22, 1-9.
Todorova, P., Arjune, S., Hendrix, C., Oehm, S., Schmidt, J. & Krauß, D. et al. (2023). Interaction between determinants governing urine volume in patients with ADPKD on tolvaptan and its impact on quality of life. Kidney International Reports. 8 8), 1616-26.
Tolvaptan. (2024). Drug information [Internet]. In: UpToDate. c2024. https://www.uptodate.com/contents/tolvaptan-drug-information.
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Grantham, J. J., Higashihara, E. et al. (2012). Tolvaptan in patients with autosomal dominant polycystic kidney disease. New England Journal of Medicine. 367(25), 2407-18.
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Perrone, R. D., Dandurand, A. et al. (2018). 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. Nephrology dialysis transplantation. 33(3), 477-89.
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Perrone, R. D., Koch, G. et al. (2017). Tolvaptan in later-stage autosomal dominant polycystic kidney disease. New England Journal of Medicine. 377(20), 1930-42.
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Perrone, R. D., Lee, J. et al. (2021). Multicenter study of long-term safety of tolvaptan in later-stage autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology. 16(1), 48-58.
Torres, V. E., Gansevoort, R. T., Perrone, R. D., Chapman, A. B., Ouyang, J., Lee, J., et al. (2021). Tolvaptan in ADPKD patients with very low kidney function. Kidney international reports. 6(8), 2171-8.
Wulfmeyer, V. C., Auber, B., Haller, H. & Schmitt, R. (2019). Comparison of different selection strategies for tolvaptan eligibility among autosomal dominant polycystic kidney disease patients. American Journal of Nephrology. 50 4), 281-90.
Zhou, X., Davenport, E., Ouyang, J., Hoke, M. E., Garbinsky, D., Agarwal, I., et al. (2022). Pooled data analysis of the long-term treatment effects of tolvaptan in ADPKD. Kidney international reports. 7(5), 1037-48. 12.
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