A comprehensive review of extrarenal manifestations of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
DOI:
https://doi.org/10.12775/QS.2025.46.66651Keywords
ADPKD, autosomal dominant polycystic kidney disease, ADPLD, ADPKD extrarenal manifestations, ADPKD liver cystsAbstract
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, primarily caused by mutations in the PKD1 and PKD2 genes. It is characterized by the progressive growth of numerous cysts in both kidneys, leading to renal failure. Beyond renal manifestations, ADPKD is associated with a wide spectrum of systemic complications, posing a significant clinical challenge and requiring comprehensive care.
Aim: The aim of this paper was a comprehensive literature review regarding the extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD), including their epidemiology, pathophysiology, and clinical significance.
Materials and Methods: The review included scientific papers sourced from the PubMed and Google Scholar databases.
Results: The most common extrarenal manifestation is autosomal dominant polycystic liver disease (ADPLD), with a prevalence reaching 94% in patients over 35; its development is strongly linked to extragenetic factors, mainly estrogen exposure. Cardiovascular manifestations are common and include hypertension (resulting, among other things, from RAAS activation), an increased frequency of aortic dilatation and aneurysms (44% of patients in one study), which raises the risk of dissection. Left ventricular hypertrophy (LVH) and valvular defects, especially mitral valve prolapse, are also frequent. Intracranial aneurysms (ICAs) occur in 9-12% of ADPKD patients (vs 3% in the general population), and their rupture tends to occur at a younger age. The most significant risk factor for ICAs is a positive family history.
Conclusions: ADPKD is a multisystemic disease, not just a renal one. The wide range of extrarenal manifestations, including hepatic, cardiovascular, and cerebrovascular complications, highlights the necessity for comprehensive screening and the implementation of holistic patient care to identify, assess, and treat all health problems associated with this disease.
References
1. Bergmann, C., Guay-Woodford, L. M., Harris, P. C., Horie, S., Peters, D. J. M., & Torres, V. E. (2018). Polycystic kidney disease. Nature reviews. Disease primers, 4(1), 50. https://doi.org/10.1038/s41572-018-0047-y
2. Chin, C. Y., Huang, W. T., Wang, J. H., Liou, J. W., Hsu, H. J., & Chen, M. C. (2024). Overview of clinical status, treatment, and long-term outcomes of pediatric autosomal-dominant polycystic kidney disease: a nationwide survey in Taiwan. Scientific reports, 14(1), 16280. https://doi.org/10.1038/s41598-024-67250-z
3. Iglesias, C. G., Torres, V. E., Offord, K. P., Holley, K. E., Beard, C. M., & Kurland, L. T. (1983). Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota: 1935-1980. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2(6), 630–639. https://doi.org/10.1016/s0272-6386(83)80044-4
4. Willey, C. J., Blais, J. D., Hall, A. K., Krasa, H. B., Makin, A. J., & Czerwiec, F. S. (2017). Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 32(8), 1356–1363. https://doi.org/10.1093/ndt/gfw240
5. Cornec-Le Gall, E., Alam, A., & Perrone, R. D. (2019). Autosomal dominant polycystic kidney disease. Lancet (London, England), 393(10174), 919–935. https://doi.org/10.1016/S0140-6736(18)32782-X
6. Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Grantham, J. J., Higashihara, E., Perrone, R. D., Krasa, H. B., Ouyang, J., Czerwiec, F. S., & TEMPO 3:4 Trial Investigators (2012). Tolvaptan in patients with autosomal dominant polycystic kidney disease. The New England journal of medicine, 367(25), 2407–2418. https://doi.org/10.1056/NEJMoa1205511
7. Carrera, P., Calzavara, S., Magistroni, R., den Dunnen, J. T., Rigo, F., Stenirri, S., Testa, F., Messa, P., Cerutti, R., Scolari, F., Izzi, C., Edefonti, A., Negrisolo, S., Benetti, E., Alibrandi, M. T., Manunta, P., Boletta, A., & Ferrari, M. (2016). Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Scientific reports, 6, 30850. https://doi.org/10.1038/srep30850
8. Hogan, M. C., Abebe, K., Torres, V. E., Chapman, A. B., Bae, K. T., Tao, C., Sun, H., Perrone, R. D., Steinman, T. I., Braun, W., Winklhofer, F. T., Miskulin, D. C., Rahbari-Oskoui, F., Brosnahan, G., Masoumi, A., Karpov, I. O., Spillane, S., Flessner, M., Moore, C. G., & Schrier, R. W. (2015). Liver involvement in early autosomal-dominant polycystic kidney disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 13(1), 155–64.e6. https://doi.org/10.1016/j.cgh.2014.07.051
9. Sanchis, I. M., Shukoor, S., Irazabal, M. V., Madsen, C. D., Chebib, F. T., Hogan, M. C., El-Zoghby, Z., Harris, P. C., Huston, J., Brown, R. D., & Torres, V. E. (2019). Presymptomatic Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN, 14(8), 1151–1160. https://doi.org/10.2215/CJN.14691218
10. Ong, A. C., Devuyst, O., Knebelmann, B., Walz, G., & ERA-EDTA Working Group for Inherited Kidney Diseases (2015). Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet (London, England), 385(9981), 1993–2002. https://doi.org/10.1016/S0140-6736(15)60907-2
11. Muto, S., Ando, M., Nishio, S., Hanaoka, K., Ubara, Y., Narita, I., Kamura, K., Mochizuki, T., Tsuchiya, K., Tsuruya, K., & Horie, S. (2020). The relationship between liver cyst volume and QOL in Japanese ADPKD patients. Clinical and experimental nephrology, 24(4), 314–322. https://doi.org/10.1007/s10157-019-01830-6
Amura, C. R., Brodsky, K. S., Gitomer, B., McFann, K., Lazennec, G., Nichols, M. T., Jani, A., Schrier, R. W., & Doctor, R. B. (2008). CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation. American journal of physiology. Cell physiology, 294(3), C786–C796. https://doi.org/10.1152/ajpcell.00457.2007
12. Sherstha, R., McKinley, C., Russ, P., Scherzinger, A., Bronner, T., Showalter, R., & Everson, G. T. (1997). Postmenopausal estrogen therapy selectively stimulates hepatic enlargement in women with autosomal dominant polycystic kidney disease. Hepatology (Baltimore, Md.), 26(5), 1282–1286. https://doi.org/10.1002/hep.510260528
13. Petrone, M., Catania, M., De Rosa, L. I., Degliuomini, R. S., Kola, K., Lupi, C., Brambilla Pisoni, M., Salvatore, S., Candiani, M., Vezzoli, G., & Sciarrone Alibrandi, M. T. (2024). Role of Female Sex Hormones in ADPKD Progression and a Personalized Approach to Contraception and Hormonal Therapy. Journal of clinical medicine, 13(5), 1257. https://doi.org/10.3390/jcm13051257
14. Abu-Wasel, B., Walsh, C., Keough, V., & Molinari, M. (2013). Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases. World journal of gastroenterology, 19(35), 5775–5786. https://doi.org/10.3748/wjg.v19.i35.5775
15. Kataoka, H., Watanabe, S., Sato, M., Manabe, S., Makabe, S., Akihisa, T., Ushio, Y., Iwasa, N., Yoshida, R., Tsuchiya, K., Nitta, K., & Mochizuki, T. (2021). Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease. Hepatology international, 15(3), 791–803. https://doi.org/10.1007/s12072-021-10176-9
16. Roediger, R., Dieterich, D., Chanumolu, P., & Deshpande, P. (2022). Polycystic Kidney/Liver Disease. Clinics in liver disease, 26(2), 229–243. https://doi.org/10.1016/j.cld.2022.01.009
17. Kuo, I. Y., & Chapman, A. B. (2019). Polycystins, ADPKD, and Cardiovascular Disease. Kidney international reports, 5(4), 396–406. https://doi.org/10.1016/j.ekir.2019.12.007
18. Oto, O. A., & Edelstein, C. L. (2024). The Pathophysiology of Left Ventricular Hypertrophy, beyond Hypertension, in Autosomal Dominant Polycystic Kidney Disease. Nephron, 148(4), 215–223. https://doi.org/10.1159/000525944
19. Vasileva, V. Y., Sultanova, R. F., Sudarikova, A. V., & Ilatovskaya, D. V. (2021). Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases. Frontiers in physiology, 12, 693130. https://doi.org/10.3389/fphys.2021.693130
20. Bouleti, C., Flamant, M., Escoubet, B., Arnoult, F., Milleron, O., Vidal-Petiot, E., Langeois, M., Ou, P., Vrtovsnik, F., & Jondeau, G. (2019). Risk of Ascending Aortic Aneurysm in Patients With Autosomal Dominant Polycystic Kidney Disease. The American journal of cardiology, 123(3), 482–488. https://doi.org/10.1016/j.amjcard.2018.10.030
21. Savis, A., Haseler, E., Beardsley, H., Chowienczyk, P. J., Simpson, J. M., & Sinha, M. D. (2024). Aortic Dilatation in Children and Young People With ADPKD. Kidney international reports, 9(5), 1210–1219. https://doi.org/10.1016/j.ekir.2024.02.007
22. Sung, P. H., Yang, Y. H., Chiang, H. J., Chiang, J. Y., Chen, C. J., Liu, C. T., Yu, C. M., & Yip, H. K. (2017). Risk of aortic aneurysm and dissection in patients with autosomal-dominant polycystic kidney disease: a nationwide population-based cohort study. Oncotarget, 8(34), 57594–57604. https://doi.org/10.18632/oncotarget.16338
23. Morningstar, J. E., Nieman, A., Wang, C., Beck, T., Harvey, A., & Norris, R. A. (2021). Mitral Valve Prolapse and Its Motley Crew-Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition. Journal of the American Heart Association, 10(13), e020919. https://doi.org/10.1161/JAHA.121.020919
24. Lumiaho, A., Ikäheimo, R., Miettinen, R., Niemitukia, L., Laitinen, T., Rantala, A., Lampainen, E., Laakso, M., & Hartikainen, J. (2001). Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1. American journal of kidney diseases : the official journal of the National Kidney Foundation, 38(6), 1208–1216. https://doi.org/10.1053/ajkd.2001.29216
25. Ebrahimi, N., Caliskan, Y., Garimella, P. S., Carriazo, S., Chebib, F. T., Bateni, G. H., Dahl, N. K., Rastogi, A., Abdipour, A., & Norouzi, S. (2025). Cardiovascular Complications in ADPKD. Kidney international reports, 10(9), 2953–2966. https://doi.org/10.1016/j.ekir.2025.06.054
26. Kuo I. Y. (2023). Defining Cardiac Dysfunction in ADPKD. Kidney360, 4(2), 126–127. https://doi.org/10.34067/KID.0000000000000066
27. Márquez-Nogueras, K. M., Vuchkovska, V., & Kuo, I. Y. (2023). Calcium signaling in polycystic kidney disease- cell death and survival. Cell calcium, 112, 102733. https://doi.org/10.1016/j.ceca.2023.102733
28. Sagar, P. S., & Rangan, G. K. (2023). Cardiovascular Manifestations and Management in ADPKD. Kidney international reports, 8(10), 1924–1940. https://doi.org/10.1016/j.ekir.2023.07.017
29. Sanchis, I. M., Shukoor, S., Irazabal, M. V., Madsen, C. D., Chebib, F. T., Hogan, M. C., El-Zoghby, Z., Harris, P. C., Huston, J., Brown, R. D., & Torres, V. E. (2019). Presymptomatic Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN, 14(8), 1151–1160. https://doi.org/10.2215/CJN.14691218
30. Walker, E. Y. X., & Marlais, M. (2023). Should we screen for intracranial aneurysms in children with autosomal dominant polycystic kidney disease?. Pediatric nephrology (Berlin, Germany), 38(1), 77–85. https://doi.org/10.1007/s00467-022-05432-5
31. Flahault, A., Trystram, D., Fouchard, M., Knebelmann, B., Nataf, F., & Joly, D. (2016). Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists. PloS one, 11(4), e0153176. https://doi.org/10.1371/journal.pone.0153176
32. Vlak, M. H., Algra, A., Brandenburg, R., & Rinkel, G. J. (2011). Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. The Lancet. Neurology, 10(7), 626–636. https://doi.org/10.1016/S1474-4422(11)70109-0
33. Izumo, T., Ogawa, Y., Matsuo, A., Okamura, K., Takahira, R., Sadakata, E., Yoshida, M., Yamaguchi, S., Tateishi, Y., Baba, S., Morofuji, Y., Hiu, T., Anda, T., & Matsuo, T. (2022). A Spontaneous Extracranial Internal Carotid Artery Dissection with Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review. Medicina (Kaunas, Lithuania), 58(5), 679. https://doi.org/10.3390/medicina58050679
34. Etminan, N., & Rinkel, G. J. (2016). Unruptured intracranial aneurysms: development, rupture and preventive management. Nature reviews. Neurology, 12(12), 699–713. https://doi.org/10.1038/nrneurol.2016.150
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Emilia Szczerek, Viktoria Płóciniczak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 105
Number of citations: 0
