Presentation: Child with non-nephrotic range proteinuria

A two-year-old boy was found to have non-nephrotic range proteinuria (serum albumin was normal) detected during clinical examination for an unrelated issue. He was otherwise well and there was no family history of kidney disease.

Consider genomic testing for:

• Steroid-resistant nephrotic syndrome presenting at any age.
• Unexplained chronic proteinuria present in early morning urine (EMU).
• Proteinuria with a histological picture of focal segmental glomerulosclerosis (FSGS) or diffuse mesangial sclerosis (DMS) on biopsy, with no identifiable cause, where a transplant or immunosuppression is planned.

• 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.
  • For an individual with proteinuria, R195 Proteinuric renal disease is most appropriate. This is a whole genome sequencing (WGS) panel used to investigate likely monogenic causes of proteinuria including nephrotic syndrome. It also contains the genes that are included in R194 Haematuria.
  • R257 Unexplained young onset end-stage renal disease: This indication should be used for patients up to the age of 36 presenting with unexplained end-stage renal disease if there is no identifiable cause detected by renal biopsy, biochemistry, imaging or clinical assessment. This WGS-based large panel may also be used if end-stage renal failure is likely or has occurred. Semi-rapid testing may be requested where cases meet eligibility criteria and where testing will provide an immediate change to treatment or clinical management for the patient, for example to inform a decision about renal transplant, therapeutic intervention or prenatal testing for an ongoing at-risk pregnancy.
• In individuals with a suspected or identifiable primary renal disorder, the specific test(s) for that disorder should be used where genetic testing is appropriate.
• The tests listed above are WGS-based. You will need to:
  • Complete an NHS GMS test order form with details of the affected child (proband) and their parents. 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).
  • Complete an NHS GMS record of discussion form for each person being tested. 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.
  • Submit parental samples alongside the child’s sample where possible to aid interpretation, especially for the larger WGS panels. Where this is not possible, for example if the child is in care and there is no access to parents, or if one parent is unavailable for testing, the child’s sample may still be submitted.
• These tests are DNA-based, so an EDTA sample (purple-topped tube) is required.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• NHS England: National Genomic Test Directory
• OMIM: Proteinuria

For patients

• infoKID (information for parents and carers of children with kidney conditions): Proteinuria