Which are the most common extrarenal manifestations of ADPKD?
Besides kidney cysts, patients with ADPKD frequently present extrarenal disease, including hepatic cysts, cysts in other organs, cardiovascular manifestations, diverticular disease, and abdominal hernias.
Polycystic liver disease (PLD) is the most common extrarenal manifestation of ADPKD and is characterized by multiple cysts distributed throughout the liver parenchyma. Hepatic cysts are commonly seen in patients with ADPKD, and their prevalence is as high as 90% on screening MRI. In a minority of patients, it can result in severe PLD requiring surgical intervention. The disease is usually found in association with ADPKD but can occur in isolation, with only a small number of kidney cysts (or even the total absence of cysts). Mutations in protein kinase C substrate 80K-H (PRKCSH) gene on chromosome 19p13 and SEC63 homologue, protein translocation regulator on chromosome 6q, account for more than 30% of isolated cases. Although most patients remain asymptomatic with preserved liver function, abdominal pain, distension, and liver decompensation may occur due to compressive effects of enlarged cysts.
Pancreatic cysts have been found in approximately 10% of patients with ADPKD. These are more prevalent with increasing age. Pancreatic cysts are nearly always asymptomatic, but in very rare occasions, cyst compression of the main pancreatic duct may cause recurrent pancreatitis. In addition, a few cases of combined ADPKD and pancreatic carcinoma have been reported, suggesting genetic interactions between ADPKD and pancreatic carcinogenesis. Asymptomatic arachnoid membrane cysts and spinal meningeal cysts have been reported in a small proportion of patients with ADPKD (8% and 2%, respectively). Arachnoid membrane cysts can increase the risk of subdural hematomas, and spinal meningeal cysts can leak and present with orthostatic headache due to intracranial hypotension.
Ovarian cysts are not associated with ADPKD, whereas cysts of the seminal vesicles occur in 40% to 60% of men with ADPKD but rarely result in infertility.
Vascular manifestations are the most important noncystic complications and include intracranial aneurysms (IAs), dolichoectasias, thoracic aortic and cervicocephalic artery dissections, and coronary artery aneurysms. They are caused by alterations in the vasculature directly linked to mutations in PKD1 or PKD2. Polycystin-1 and polycystin-2 are known to be expressed in vascular smooth muscle cells. IAs represent the most feared vascular manifestation of ADPKD because their rupture carries a 35% to 55% risk of combined severe morbidity and mortality. The rate of IA in ADPKD patients ranges from 6% (negative family history of IA) to 16% (positive family history of IA), approximately five times more common than in the general population (1% to 2%). They are often asymptomatic (Irazabal et al., 2015). However, focal findings such as cranial nerve palsy or seizure may result from compression of local structures.
Cardiac valvular abnormalities are common in patients with ADPKD. Mitral valve prolapse is the most frequent valvular abnormality found in up to 25% of patients on echocardiography, whereas aortic regurgitation and tricuspid prolapse may occur in a small proportion. Nevertheless, they rarely require valve replacement, and screening echocardiography is not indicated unless a cardiac murmur is detected on clinical examination.
The prevalence of colonic diverticulosis and diverticulitis in patients with ESKD with ADPKD is significantly higher than in individuals with other kidney diseases (83% vs. 32%). However, whether ADPKD patients with preserved kidney function show propensity for diverticular disease remains unknown. The mechanisms implicated in the development of colonic diverticula may include alterations in polycystin function, which can exacerbate aging-induced smooth muscle dysfunction.
Abdominal hernias (inguinal, incisional, and paraumbilical) are frequent in the ADPKD population. Importantly, hernias are associated with complications (intestinal incarceration or strangulation) and may cause problems in patients undergoing peritoneal dialysis.
