Genetic forms and clinical clues
ADTKD-UMOD (uromodulin):
- Commonest form
- Early-onset gout, often in teens/twenties
- CKD progression variable, kidney failure typically 40s-70s
- Hyperuricaemia disproportionate to eGFR
- Bland urine
ADTKD-MUC1 (mucin-1):
- No gout characteristically
- Slowly progressive CKD
- Diagnosis missed historically — requires long-read sequencing or specialised VNTR assay
ADTKD-REN (renin):
- Childhood onset
- Hyperkalaemia, hyperuricaemia, anaemia (early), hypotension
- Mild CKD in childhood, progression later
- Avoid ACE/ARB — can precipitate AKI and severe hyperkalaemia
ADTKD-HNF1B (hepatocyte nuclear factor 1-beta):
- Often syndromic: MODY5 diabetes, pancreatic atrophy, genital tract anomalies, hypomagnesaemia, hyperuricaemia
- Renal cysts, dysplasia, hypoplasia possible
- De novo mutations common — family history may be absent
- Often picked up antenatally on fetal anomaly scan
Adtkd-sec61a1
- Rare; immunodeficiency and neutropenia in some
Adtkd-undetermined
- ~25% remain genetically unclassified; ongoing research
Investigation and diagnosis
When To Suspect
- Slowly progressive CKD
- Family history of kidney failure, especially over multiple generations
- Bland urine: ACR <30 mg/mmol, no haematuria
- Normal-sized kidneys on ultrasound (or minor cystic change)
- Early-onset gout
- Unexplained hypomagnesaemia, hyperuricaemia, MODY-like diabetes (HNF1B)
First-line Tests
- Urea, creatinine, eGFR, electrolytes (Mg, urate, K)
- Urine ACR, PCR, microscopy
- Renal ultrasound
- Family history with detailed pedigree
GENETIC TESTING (NHS Genomic Medicine Service):
- R193 — cystic kidney disease panel covers UMOD, REN, HNF1B, SEC61A1
- MUC1 — request specifically; specialised lab (often Newcastle, Leicester)
- Refer to clinical genetics for counselling before testing
- Useful for: confirming diagnosis, family screening, living donor assessment
Biopsy
- Rarely needed in 2026 — genetics is first-line
- Shows tubulointerstitial fibrosis, tubular atrophy, no/minimal glomerular disease
- Uromodulin accumulation in UMOD; MUC1 deposits in MUC1 (specialist immunostaining)
Differential
- ADPKD (cystic kidneys) — see PKD page
- Alport syndrome (haematuria, hearing loss)
- Nephronophthisis (childhood/adolescent)
- Lithium nephropathy
- Chronic obstructive uropathy
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Management
General CKD Care
- BP target <130/80; ACE inhibitor or ARB if proteinuric — AVOID in ADTKD-REN unless under specialist care
- Statin per QRISK / KDIGO
- Cardiovascular risk reduction
- Salt restriction
- Avoid NSAIDs, aminoglycosides, contrast where possible
- Vaccinations as for CKD
Gout
- Allopurinol first-line; titrate to urate <360 μmol/L (<300 in tophaceous)
- Febuxostat as alternative
- Colchicine for flares (dose-adjust for eGFR)
- Avoid NSAIDs for flares — use prednisolone or colchicine
- Prophylactic colchicine for 6 months when starting urate-lowering therapy
Adtkd-ren Specific
- Maintain hydration
- Avoid ACE/ARB, diuretics, NSAIDs — all worsen kidney function
- Fludrocortisone may be considered in some patients (specialist)
- Monitor for hyperkalaemia, anaemia (treat with ESA + iron)
Adtkd-hnf1b Specific
- Screen for diabetes (HbA1c annually) and treat per MODY5 guidance — often needs insulin earlier than expected
- Magnesium replacement
- Pelvic ultrasound for genital tract anomalies
- Hyperuricaemia management
Family Screening
- Cascade genetic testing through clinical genetics
- At-risk relatives offered eGFR, urine ACR, BP and genetic test
- Particularly important before any living kidney donation in the family
Kidney Transplant
- Excellent outcomes — no disease recurrence (ADTKD does not recur in graft)
- Living-related donation possible — but donor MUST have genetic testing first to exclude the mutation
Outlook and emerging therapies
Prognosis
- Highly variable between and within families
- Most reach kidney failure between 40 and 70 years
- Some patients have stable mild CKD into their 80s
- ADTKD-REN tends to have an earlier childhood presentation but slower CKD progression
Emerging Therapies
- UMOD-targeted approaches in early trials
- MUC1: small-molecule chaperones (BRD4780) reduce mutant MUC1 accumulation in preclinical work
- Gene therapy approaches in research
- Patient registries (e.g. RaDaR rare renal disease registry, UK) help identify trial candidates
What To Tell Families
- Inheritance is autosomal dominant — 50% risk to each child
- Variable severity; cannot predict precisely from one family member to another
- Genetic counselling supports reproductive choices including pre-implantation genetic testing (PGD)
KEY MESSAGE: ADTKD is now a treatable diagnosis — not in the sense of disease-modifying drugs, but in the sense that confirming it allows targeted CKD care, gout control, family screening and safe transplant planning.
