Autosomal Dominant Polycystic Kidney Disease in Older Adults

Dear Editor,

While the epidemiology and clinical characteristics of autosomal dominant polycystic kidney disease (ADPKD) in children and younger adults are clearly defined, it is much less so for older adults.¹ This may be explained by the fact that older adults living with ADPKD are difficult to screen, as many have milder forms of disease with subtle clinical presentations. ADPKD patients who have more severe forms of the disease may not survive to old age, with complications such as cardiovascular events and septic infections resulting in early mortality. Observational studies detailing the clinical characteristics of the older ADPKD population are lacking, but the two published studies by Milutinovic et al.² in the USA and Helal et al.³ in Tunisia have both concurred that ADPKD diagnoses in older adults are often made late, when patients are already diagnosed with kidney failure. Indeed, these trends are backed up by ascertainment of the prevalent genetic profile in older ADPKD cohorts, in which disease harboring PKD2 gene mutations were common.⁴ PKD2 mutation produces a milder form of disease, with the mean age of kidney failure occurring approximately 20 years later than ADPKD with PKD1 mutation.⁴ Disease modification trials typically excluded patients aged >55, hence the impact of treatment in older adults with ADPKD is still relatively uncertain.⁵ It will likely require several years for therapies to show any efficacy toward renal endpoints of these patients, which makes investigation challenging. Moreover, potential therapies often have important side effects, and benefits of treatment, if any, will unlikely outweigh risks in this patient population. Going forward, further comprehensive data in diverse populations is anticipated to determine potential solutions for earlier ADPKD identification and establish strategies to reduce progression of disease in older patient cohorts.