Polycystic Kidney Disease (PKD)

ADPKD—what the radiologist should know

Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort

DPKD is most commonly caused by mutations in the PKD1 and PKD2 gene loci, with approximately 78% of patients exhibiting PKD1 mutations and abnormal polycystin-1 function. Polycystin-1 is a transmembrane mechanosensor located on primary cilia in renal tubule cells. Polycystin-2 is the gene product encoded by PKD2 and is a calcium channel closely associated with polycystin-1. Patients with PKD1 mutations are more likely to have earlier-onset disease than those with PKD2 mutations. Studies have shown that having a family member who developed ESRD by age 55 had a positive predictive value of 100% for a PKD1 mutation. Although most patients with ADPKD remain asymptomatic until the fourth decade of life, childhood-onset ADPKD has been increasingly commonly diagnosed and may be incidentally discovered.

Abnormal tuberin function is implicated in tuberous sclerosis complex (TSC). Patients with TSC have a number of systemic manifestations. In the kidney, TSC frequently manifests as angiomyolipomas. Because the TSC2 and PKD1 genes are adjacent, patients with deletions involving both genes may present with manifestations of both TSC and ADPKD. In this case, the patient has no other clinical manifestations of TSC.

A mutation in the UMOD gene, encoding uromodulin, is the most common cause of autosomal dominant tubulointerstitial kidney disease (ADTKD), a disease that also causes slowly progressive cystic kidney disease, but kidney size is smaller and not marked by the large cysts of ADKPD.

Mutations in PKHD1 genes lead to defects in fibrocystin and cause autosomal recessive polycystic kidney disease (ARPKD), which usually presents in children and adolescents. Although this patient presented at age 6, his CT scan shows large cysts in the kidneys and liver. Although ARPKD is also associated with liver involvement, this more commonly manifests as cystic dilation of biliary ducts (Caroli disease), with hepatobiliary fibrosis, recurrent cholestasis, and portal hypertension, rather than overt cystic liver. Additionally, patients with ARPKD typically demonstrate large, echogenic kidneys on ultrasound without discrete cysts.

Gimpel C, Bergmann C, Bockenhauer D, et al: International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people. Nat Rev Nephrol 15(11): 713‒726, 2019

Avni FE, Guissard G, Hall M, et al: Hereditary polycystic kidney diseases in children: changing sonographic patterns through childhood. Pediatr Radiol 32(3): 169‒174, 2002

Eckardt KU, Alper SL, Antignac C, et al: Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management—a KDIGO consensus report. Kidney Int 88(4): 676‒683, 2015

Barua M, Cil O, Paterson AD, et al: Family history of renal disease severity predicts the mutated gene in ADPKD. J Am Soc Nephrol 20(8): 1833‒1838, 2009

Crino PB, Nathanson KL, Petri Henske E: The tuberous sclerosis complex. N Engl J Med 355(13): 1345‒1356, 2006