Otomozal dominant polikistik böbrek hastalığında tolvaptan kullanımı: Tek merkez deneyimi

Year 2023, , 323 - 328, 28.09.2023

Cebrail Karaca , Mevlut Tamer Dincer

https://doi.org/10.21673/anadoluklin.1343396

Abstract

Amaç: Otozomal dominant polikistik böbrek hastalığı (ODPBH) son dönem böbrek hastalığına (SDBH) ilerleyen, sık görülen bir genetik hastalıktır. Tolvaptan ODPBH’de kist büyümesini ve böbrek hastalığı progresyonunu yavaşlatan bir hastalık modifiye edici ajandır. Bu çalışmada tolvaptan kullanan yüksek riskli ODPBH hastalıklarda tolvaptanın etki ve yan etkilerini inceledik. Bu çalışmaya ait deneyimimizi paylaşıyoruz.

Yöntemler: Mayo Klinik Sınıflaması’na göre yüksek riskli olan ve tedaviyi kabul eden 27 ODPBH hastası çalışmaya dâhil edildi. Hastalara ODPBH’yı yavaşlatmak için tolvaptan 60 mg/gün ağız yoluyla başlandı. Hastaların tolvaptan tedavisine cevabına ve yan etkilerini tolere edebilmelerine bağlı olarak günlük doz 120 mg’ye arttırıldı. Hastalar tolvaptan tedavisi süresince ilacın etki ve yan etkilerini gözlemlemek için takip edildi.

Bulgular: Hastaların ortalama yaşı 40,3±8,2 idi. Hipertansiyon hastaların %81,5’inde vardı ve çoğunlukla renin anjiyotensin aldosteron sistemi inhibitörlerini kullanıyorlardı. Tolvaptan tedavisinin aquaretik yan etkileri olarak; 14 hastada (%51,9) susama, 10 hastada (%37) polidipsi, 5 hastada (%18,5) ağız kuruluğu, 4 hastada (%14,8) noktüri vardı. Ek olarak birer hastada karaciğer enzim yüksekliği, hipernatremi ve akut böbrek hasarı gözlenmesine rağmen bu yan etkiler kalıcı olarak ilacın kesilmesine neden olmadı. Bütün hastalarda poliüri görüldü, ancak hastalar poliüriyi iyi tolere ederek tolvaptan tedavisini kullanmaya devam etti.

Sonuç: Hastalarda tolvaptan tedavisine bağlı yan etkiler görülmesine rağmen hiçbir hasta ilacı kalıcı olarak bırakmadı. Hastaların genel olarak tolvaptan tedavisini iyi tolere ettiğini gözlemledik.

Keywords

Otozomal baskın polikistik böbrek hastalığı, poliüri, tolvaptan, yan etkiler

Use of tolvaptan in autosomal polycystic kidney disease: A single center experience

Abstract

Aim: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease that progresses to end-stage renal disease (ESRD). Tolvaptan is a disease-modifying agent that slows cyst growth and kidney disease progression in ADPKD. In this study, we examined the effects and side effects of tolvaptan in high-risk ADPKD patients using tolvaptan. We share our experience of this study.

Methods: Twenty-seven ADPKD patients who were at high risk according to the Mayo Clinical Classification and accepted treatment were included in the study. Tolvaptan 60 mg/day orally was started in patients to slow the ADPKD. The daily dose was increased to 120 mg depending on the patients’ response to tolvaptan treatment and their tolerance to side effects. The patients were followed up during tolvaptan treatment to observe the effects and side effects of the medication.

Results: The mean age of the patients was 40.3±8.2. Hypertension was present in 81.5% of the patients, and they mostly used renin angiotensin aldosterone system inhibitors. As aquaretic side effects of tolvaptan treatment, there was thirst in 14 patients (51.9%), polydipsia in 10 patients (37%), dry mouth in 5 patients (18.5%), and nocturia in 4 patients (14.8%). In addition, although liver enzyme elevation, hypernatremia, and acute kidney injury were observed in one patient each, these side effects did not lead to permanent discontinuation of the drug. Polyuria was observed in all patients, but the patients tolerated the polyuria well and continued to use tolvaptan treatment.

Conclusion: Although the patients experienced side effects related to tolvaptan treatment, none of the patients discontinued the drug permanently. We observed that patients generally tolerated tolvaptan treatment well.

Keywords

Autosomal dominant polycystic kidney disease, polyuria, side effects, tolvaptan

References

• Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393(10174):919-35.
• Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 2009;76(2):149-68.
• Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369(9569):1287-301.
• Seyahi N, Koçyiğit İ, Ateş K. Current status of kidney replacement therapy in Türkiye: A summary of 2021 Turkish society of nephrology registry report. Turk J Nephrol. 2023;32(3):174-180.
• Irazabal MV, Rangel LJ, Bergstralh EJ, et al. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015;26(1):160-72.
• Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407-18.
• Torres VE, Chapman AB, Devuyst O, et al. 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.
• Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. N Engl J Med. 2017;377(20):1930-42.
• Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol. 2009;5(4):221-8.
• Ecder T. Cardiovascular complications in autosomal dominant polycystic kidney disease. Curr Hypertens Rev. 2013;9(1):2-11.
• Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT. Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. Hepatology. 1990;11(6):1033-7.
• Torres VE, Harris PC. Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol. 2014;25(1):18-32.
• Devuyst O, Chapman AB, Shoaf SE, Czerwiec FS, Blais JD. Tolerability of Aquaretic-Related Symptoms Following Tolvaptan for Autosomal Dominant Polycystic Kidney Disease: Results From TEMPO 3:4. Kidney Int Rep. 2017;2(6):1132-40.
• Anderegg MA, Dhayat NA, Sommer G, et al. Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients Treated With Tolvaptan. Kidney Med. 2020;2(2):162-71.
• Chebib FT, Perrone RD, Chapman AB, et al. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol. 2018;29(10):2458-70.
• Torres VE, Chapman AB, Devuyst O, et al. 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.
• Endo M, Katayama K, Matsuo H, et al. Role of Liver Transplantation in Tolvaptan-Associated Acute Liver Failure. Kidney Int Rep. 2019;4(11):1653-7.
• Devuyst O, Chapman AB, Gansevoort RT, et al. Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial. J Am Soc Nephrol. 2017;28(5):1592-602.