Presentation: Adult with unexpected finding of multiple kidney cysts

A 68-year-old man has been found to have multiple kidney cysts during an ultrasound scan for symptoms of biliary colic. He has no personal or family history of kidney disease but had hypertension for nine years. The kidneys were slightly enlarged but no liver cysts were identified.

Genomic testing should be considered in patients with non-syndromic cystic renal disease (excluding acquired cystic disease due to chronic or end-stage kidney disease) in the following instances:

• When the disease is not clinically characteristic of autosomal dominant polycystic kidney disease (ADPKD) and underlying diagnosis is required for management purposes, for example determining suitability of tolvaptan therapy, referral for preimplantation genetic testing for monogenic conditions (PGT-M) or referring a family member for predictive (also known as presymptomatic) testing.
• When clinically symptomatic disease has presented in the patient before the age of 18.

Where a clinical diagnosis of ADPKD has been made and genetic diagnosis is required to influence management, for example to select disease-specific therapies, refer for PGT-M or for living-related donor assessment.

• Consult the National Genomic Test Directory. Here you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our Knowledge Hub resource ‘Genomic testing in the devolved nations’.
  • To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed-Off Panels Resource.
• Decide which of the panels best suits the needs of your patient/family:
  • R193 Cystic renal disease: This indication uses whole genome sequencing (WGS) to analyse a large panel of genes associated with kidney cysts and should be used for patients who fall into the categories detailed above.
  • R27 Paediatric disorders and R89 Ultra-rare and atypical monogenic disorders: These indications may be considered for individuals with complex or syndromic presentations. R27 includes microarray and a WGS ‘super-panel’. R89 includes microarray and WGS panels selected by the requesting clinician. Both tests currently require authorisation from clinical genetics.
  • R240 Diagnostic testing for known mutation(s): This indication can be used when a patient is clinically affected with cystic renal disease if a member of the family already has a known pathogenic or likely pathogenic variant. In this situation, the laboratory will only test for the known familial variant.
  • R242 Predictive testing for known familial mutation(s): This is a predictive test to be used for unaffected individuals where a pathogenic or likely pathogenic variant has already been identified in a relative. This test can only be requested by clinical genetics.
• For WGS-based tests, including R193, R27 and R89 you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband). Include details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see how to complete a test order form for WGS for support); and
  • complete an NHS GMS record of discussion form for each person being tested. (This is typically one form for an affected individual, but if you are undertaking trio testing of an affected individual and their parents, you will need to complete three forms.)  See how to complete a record of discussion form for support.
• For tests that do not include WGS, including R240 and R242:
  •  You can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
  • When testing in children, parental samples may be needed for interpretation of the proband’s result, for example to determine whether a variant is de novo or inherited. These samples may be requested by the testing laboratory or you may wish to contact clinical genetics.
• These tests are DNA-based, so an EDTA sample (purple-topped tube) is required.

For patients

• GeneReviews: Autosomal dominant polycystic kidney disease
• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• KDIGO: Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• MedlinePlus: Polycystic kidney disease
• NHS England: National Genomic Test Directory
• Orphanet (information about rare diseases and orphan drugs)

For patients

• Kidney Care UK: Autosomal dominant polycystic kidney disease (ADPKD)
• Kidney Research UK: What is polycystic kidney disease? 
• NHS Health A to Z: Autosomal dominant polycystic kidney disease
• PKD Foundation: What is polycystic kidney disease?
• Polycystic Kidney Disease Charity