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 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. From this link 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 Genomic testing in the devolved nations.
  • For information about the genes that 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 most of 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.
• For tests that are undertaken using WGS, including R195 and R257, you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents, including 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 (RoD) form for each person being tested – for example, if you are undertaking trio testing of an affected individual and their parents, you will need three RoD forms (see How to complete a RoD form for support); and
  • submit parental samples alongside the child’s sample to aid interpretation, especially for the larger WGS panels (where this is not possible, for example because the child is in care or the parents are unavailable for testing, the child may be submitted as a singleton).
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

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