As frequently as 1 in 500 people are afflicted with an inherited kidney disorder called Autosomal Dominant Polycystic Kidney Disease (ADPKD). Caused mainly by mutations in the PKD1 or PKD2 genes, ADPKD accounts for approximately 5-10% of individuals who develop end-stage renal disease by age 60 and require renal replacement therapy.
While there is widely varied severity of phenotypes and age of disease onset, even within the same family, individuals invariably develop fluid-filled cyst growth in both kidneys that increase in number and size over their lifetime, causing a progressive loss in kidney function and enlargement of the kidneys. Individuals also frequently develop other complications such as high blood pressure, chronic back pain, and urinary tract infections.
ADPKD is a fully penetrant disease, meaning individuals who inherit a mutated PKD gene will develop kidney cysts that can be detected sonographically by age 30. Although inherited diseases such as ADPKD cannot be prevented, individuals planning on having children can seek genetic counselling to assess their risk of passing the disease to their offspring. In addition, maintaining good health may help prevent some of the complications of ADPKD, such as keeping blood pressure in check by eating a low-salt diet and maintaining a healthy weight.
Scientists are still attempting to elucidate the mechanisms causing cyst growth, but dysregulated cellular processes such as hyper-proliferation of renal epithelial cells and uncontrolled fluid secretion have been identified to play major roles. With only 1 FDA-approved medication, Tolvaptan, that is effective in only a subset of patients, there remains an urgent need to uncover further therapeutic avenues.
References:
Chebib, F. T., & Torres, V. E. (2016). Autosomal Dominant Polycystic Kidney Disease: Core Curriculum 2016. Am J Kidney Dis, 67(5), 792-810.
Igarashi, P., & Somlo, S. (2002). Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol, 13(9), 2384-2398. https://doi.org/10.1097/01.asn.0000028643.17901.42
Lanktree, M. B., Haghighi, A., di Bari, I., Song, X., & Pei, Y. (2021). Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic Studies. Clin J Am Soc Nephrol, 16(5), 790-799. https://doi.org/10.2215/CJN.02320220
Luciano, R. L., & Dahl, N. K. (2014). Extra-renal manifestations of autosomal dominant polycystic kidney disease (ADPKD): considerations for routine screening and management. Nephrol Dial Transplant, 29(2), 247-254. https://doi.org/10.1093/ndt/gft437
Muller, R. U., Messchendorp, A. L., Birn, H., Capasso, G., Cornec-Le Gall, E., Devuyst, O., van Eerde, A., Guirchoun, P., Harris, T., Hoorn, E. J., Knoers, N., Korst, U., Mekahli, D., Le Meur, Y., Nijenhuis, T., Ong, A. C. M., Sayer, J. A., Schaefer, F., Servais, A., . . . Gansevoort, R. T. (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. Nephrol Dial Transplant, 37(5), 825-839.
https://doi.org/10.1093/ndt/gfab312 Assessed and Endorsed by the MedReport Medical Review Board