adult polycystic kidney disease - diagnostic considerations

Last edited 12/2019

How autosomal dominant polycystic kidney disease affects the kidneys

• 1. Hypertension
• 2. Acute and chronic pain
• 3. Cyst and urinary tract infections
• 4. Hematuria
• 5. Kidney stones
• 6. Urine concentration defects
• 7. Loss of renal function

Cyst enlargement results in an exponential increase in total kidney volume (TKV; expressed relative to height (htTKV)) and often results in ESRD

Clinical symptoms, including early-onset hypertension, abdominal fullness and pain, haematuria and urinary tract infections (UTIs)

• are usually first observed decades (sometimes even in childhood) before the onset of renal insufficiency

ADPKD diagnosis is made on the basis of imaging.

• ultrasonography is the imaging modality of choice for pre-symptomatic diagnosis
  • age-dependent ultrasound criteria for both diagnosis and disease exclusion have been established for patients with a positive family history (1)
    • for PKD1 and PKD2 individuals
      • the presence of three or more renal cysts (unilateral or bilateral) for establishing the diagnosis for at-risk individuals 15-39 years;
      • four (two or more cysts in each kidney) for individuals 40-59 years;
      • and eight (four or more cysts in each) for individuals who are 60 years or older
        
        
  • ultrasonography is the most common and least expensive imaging method, but CT or MRI can provide more quantitative data (that is, htTKV) of prognostic value
  • Ultrasonography criteria for an ADPKD diagnosis in at-risk individuals

  Age	PKD1 mutation	PKD2 mutation	Unknown ADPKD genotype
  15-30 years	>=3 cysts(a) • PPV = 100% • SEN = 94.3%	• >=3 cysts (a) • PPV = 100% • SEN = 69.5%	• >=3 cysts (a) • PPV = 100% • SEN = 81.7%
  30-39 years	>=3 cystsa • PPV = 100% • SEN = 96.6%	•> =3 cystsa • PPV=100% • SEN = 94.9%	• >=3 cystsa • PPV=100% • SEN = 95.5%
  40-49years	• >=2 cysts in each kidney • PPV = 100% • SEN = 92.6%	• >=2 cysts in each kidney • PPV = 100% • SEN = 88.8%	• >=2 cysts in each kidney • PPV = 100% • SEN = 90%

Advances in renal imaging (magnetic resonance imaging MRI and high-resolution ultrasound) might help with disease exclusion in at-risk individuals.

A study suggested that MRI showing >10 cysts in patients younger than 30 years is 100% sensitive and specific for the diagnosis of ADPKD (2)

Genetic testing is not done as part of standard care and is helpful to assess potential living related kidney donors with negative or equivocal scans and detect rare forms of ADPKD and other cystic diseases (3,4).

Prenatal screening.

• as ADPKD is an adult-onset disease, prenatal screening is not commonly carried out, but there is increasing interest in this procedure, especially from families with experience of early-onset renal disease or early ICAs. Of note, affected families with children with early-onset ADPKD have a high risk of subsequent children also having early and severe ADPKD, and this information should be shared with affected families
• preimplantation genetic diagnosis is available for ADPKD, including analysis of the duplicated PKD1 locus, and may be more commonly sought in the future

Reference:

• 1) Pei Y, Obaji J, Dupuis A, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol. 2009;20(1):205-212
• 2) Pei Y, Hwang Y-H, Conklin J, et al. Imaging-based diagnosis of autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2015;26(3):746-753.
• 3) Nguyen A-NT, Wallace DP, Blanco G. Ouabain binds with high affinity to the Na,K-ATPase in human polycystic kidney cells and induces extracellular signal-regulated kinase activation and cell proliferation. J Am Soc Nephrol. 2007;18(1):46-57.
• 4) Cornec-Le Gall E, Chebib FT, Madsen CD, et al. The value of genetic testing in polycystic kidney diseases illustrated by a family with PKD2 and COL4A1 mutations. Am J Kidney Dis. 2018;72(2):302-308.