• Test code: 04115
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Polycystic Kidney Disease Type 2 Panel

Test description

The Invitae Polycystic Kidney Disease Panel evaluates PKD2 and PKHD1, which are two genes that are known to be associated with polycystic kidney disease, type 2 (PKD). PKD2 is associated with autosomal dominant polycystic kidney disease (ADPKD) and PKHD1 is associated with autosomal recessive polycystic kidney disease (ARPKD).

For at-risk individuals and individuals with clinical features consistent with PKD, identifying a pathogenic variant in one of these two genes early increases the chances of successful treatment of the liver, renal, vascular, and pulmonary manifestations that are associated with ADPKD and ARPKD. Genetic testing can help determine what surveillance and treatments are appropriate, provide a patient information on which agents to avoid, and guide lifestyle-modification, family-planning, and intervention recommendations. It may also increase the amount of time that a patient has to select unaffected family member for donor transplantation.

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Primary panel (2 genes)

Alternative tests to consider

Polycystic kidney disease is a member of a class of disorders called ciliopathies. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone. Depending on the individual’s clinical and family history, the broader Invitae Ciliopathies Panel may be appropriate. It can be ordered at no additional cost.

  • autosomal dominant polycystic kidney disease (ADPKD)
    • autosomal dominant polycystic kidney disease type 2
  • autosomal recessive polycystic kidney disease (ARPKD)

This test does not include analysis of the PKD1 gene.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by pathogenic variants in the PKD1 and PKD2 genes. It is characterized by the formation of cysts in the kidneys. Cysts can also develop in several organs outside of the kidneys, including the liver, pancreas, seminal vesicles, and arachnoid membranes. Additional clinical features and complications include end stage renal disease, hypertension, vascular abnormalities, cardiac valve malformations (aortic root dilatation and mitral valve prolapse), abdominal wall hernias, and chronic abdominal pain.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by pathogenic variants in the PKHD1 gene. ARPKD is characterized by cyst formation in the kidneys and by liver abnormalities associated with congenital hepatic fibrosis. Symptoms may include enlarged kidneys (nephromegaly), an enlarged liver (hepatomegaly), dilated biliary ducts, and abnormal fetal pulmonary development during pregnancy.

Large population studies of families with ADPKD have pathogenic variants that have been identified in PKD1 or PKD2. Of the individuals with identified pathogenic variants, approximately 85% are have variants in PKD1 and approximately 15% have variants in PKD2. It should be noted that the Invitae Polycystic Kidney Disease panel does not include analysis of the PKD1 gene.

Sequencing the PKHD1 gene identifies pathogenic variants in approximately 77%-79% of individuals who survived the neonatal period.

PKD2 is associated with autosomal dominant polycystic kidney disease.
PKHD1 is associated with autosomal recessive polycystic kidney disease.

ADPKD is highly penetrant, typically begins to manifest in adulthood, and can present with variable symptoms and levels of severity. The majority of individuals with ADPKD will develop end stage kidney failure during their lifetime, requiring dialysis and an eventual kidney transplant. Individuals with pathogenic variants in PKD1 typically experience end stage renal disease by the age of 70, though approximately 50% of individuals with pathogenic variants in PKD2 still have functioning kidneys at 70. Significant intra- and interfamilial variability exists, which is likely due to genetic and environmental modifiers.

ARPKD is a fully penetrant, severe multisystemic disorder whose symptoms often begin to manifest prenatally or in infancy. Morbidity and mortality in infancy is as much as 30% and is a result of pulmonary insufficiency and infections. Infants who survive the neonatal period are at risk to develop end stage renal disease and hepatobiliary disease in the first decade of life.

The prevalence of ADPKD at birth is between 1 in 400 and 1 in 1,000 individuals. ADPKD affects over 12 million people worldwide and is responsible for 10% of end stage renal disease cases.

The prevalence of ARPKD in live births is estimated at 1 in 20,000. The carrier frequency in the general population is 1 in 70 individuals.

Radiology findings are typically used to establish a clinical diagnosis of ARPKD and ADPKD. Genetic testing should be considered to confirm the diagnosis, clarify uncertain radiology results, establish recurrence risk, provide disease prognosis, and to potentially screen living donors for transplantation.

As ADPKD is typically an adult onset disorder. Please consider guidelines and position statements from the American College of Medical Genetics (ACMG), the National Society of Genetic Counselors (NSGC), and the American Academy of Pediatrics (AAP) when testing minors.

  1. Audrézet, MP, et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum. Mutat. 2012; 33(8):1239-50. doi: 10.1002/humu.22103. PMID: 22508176
  2. Rossetti, S, et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 2007; 18(7):2143-60. doi: 10.1681/ASN.2006121387. PMID: 17582161
  3. Gunay-Aygun, M, et al. PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis. Mol. Genet. Metab. 2010; 99(2):160-73. doi: 10.1016/j.ymgme.2009.10.010. PMID: 19914852
  4. Sweeney, WE, Avner, ED. Polycystic Kidney Disease, Autosomal Recessive. 2001 Jul 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1326/ PMID: 20301501
  5. Ross, LF, et al. Technical report: Ethical and policy issues in genetic testing and screening of children. Genet. Med. 2013; 15(3):234-45. doi: 10.1038/gim.2012.176. PMID: 23429433
  6. Harris, PC, Torres, VE. Polycystic Kidney Disease, Autosomal Dominant. 2002 Jan 10. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1246/ PMID: 20301424
  7. Committee on Bioethics. Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013; 131(3):620-2. doi: 10.1542/peds.2012-3680. PMID: 23428972
  8. Bergmann, C, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005; 67(3):829-48. doi: 10.1111/j.1523-1755.2005.00148.x. PMID: 15698423
  9. Chapman, AB, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015; 88(1):17-27. doi: 10.1038/ki.2015.59. PMID: 25786098
  10. Torres, VE, et al. Autosomal dominant polycystic kidney disease. Lancet. 2007; 369(9569):1287-301. doi: 10.1016/S0140-6736(07)60601-1. PMID: 17434405

No management guidelines are currently published for ADPKD and ARPKD. However, in 2015, the Kidney Disease: Improving Global Outcomes Controversies Conference (KDIGO) published a summary on areas of consensus and controversy surrounding ADPKD management, treatment, and evaluation, with the goal of further developing standards of care:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PKD2 NM_000297.3
PKHD1 NM_138694.3