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Abstract: TH-PO375

Clinical Characterization of Monoallelic-PKHD1 Subjects

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Jawaid, Tabinda, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Senum, Sarah R., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Madsen, Charles D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

ARPKD results from biallelic pathogenic variants of PKHD1. There is also limited literature indicating that monoallelic PKHD1 variants can develop kidney and/or liver cysts. We aimed to characterize patients with monoallelic-PKHD1 identified from ARPKD families or from genetic screening of subjects with kidney and/or liver cysts.


Genetic testing was performed using a target next-generation sequencing panel consisting of known PKD and ciliopathy genes and segregation was performed by Sanger sequencing. Individuals with single defined pathogenic or likely pathogenic PKHD1 variants were characterized by imaging and the clinical phenotype determined from chart review; ones with other significant genetic variants were excluded.


A total of 28 monoallelic-PKHD1 subjects with complete clinical and imaging details were identified; 6 from ARPKD families and 22 from genetic screening. Females accounted for 57.1% (16/28) with a median age at diagnosis of 48 years (range 1.2-74). Only kidney cysts were found in 32.1% (9/28), 7.1% (2/28) had only liver cysts, and 60.7% (17/28) had cysts in both organs, with the number of cysts ranging from 1 to >20. Ten subjects were initially diagnosed following imaging for related symptoms: flank pain (6/22), hematuria (3/22), or abnormal physical examination (1/22). However, the majority (18/28) were diagnosed incidentally, with imaging performed for donor evaluation or reasons unrelated to cystogenesis. Hypertension was found in 57.1% (16/28). Two subjects (5.7%) with other kidney comorbidities had a kidney transplant, and 17.8% (5/28) were kidney donors, although a few cysts were present. The median eGFR was 60 mL/min/1.73m2 (range 5-126), and only one patient died, at the age of 71. Other phenotypes included nephrolithiasis (35.7%), pancreatic cysts (7.1%), renal mass resulting in nephrectomy (7.1%), intracranial aneurysm (3.5%), and medullary sponge kidney (3.5%). The type of pathogenic variant was truncating in 35.7% (10/28) and non-truncating in 64.2% (18/28).


Monoallelic pathogenic PKHD1 variants have a variable clinical impact and are not usually associated with a decline in kidney function but may account for a significant group of individuals diagnosed with kidney and/or liver cysts. Limited evidence of multiple family members being affected suggests reduced expressivity of the phenotype.


  • NIDDK Support