PRIMEVIEW

ADTKD
For the Primer, visit doi:10.1038/s41572-019-0109-9

Autosomal dominant tubulointerstitial REN mutations affect synthesis, EPIDEMIOLOGY

MECHANISMS glycosylation and secretion of
kidney disease (ADTKD) is a group prorenin and renin
of rare diseases characterized by tubular As ADTKD is rare, and a diagnosis requires
damage and interstitial fibrosis but confirmation by genetic testing, the exact
without glomerular lesions. ADTKD ADTKD is caused incidence and prevalence are not known. However,
inescapably, albeit slowly, progresses to by mutations in at • Anaemia recent data suggest that ADTKD is one of the
end-stage renal disease (ESRD). least 5 different genes • Hypotension most common monogenic kidney diseases after
• Hyperkalaemia autosomal dominant polycystic kidney disease. A
• Gout
• ESRD survey of a single centre in England estimated the
prevalence of ADTKD at 16 per million population
DIAGNOSIS
UMOD mutations cause the and ADTKD-UMOD at 9 per million population.
corresponding protein uromodulin
ADTKD should be suspected in an individual to fold incorrectly, leading to its
accumulation in the endoplasmic
with a family history compatible with dominant reticulum (ER)
inheritance of chronic kidney disease (CKD), a OUTLOOK
MUC1HTCOGUJKȎOWVCVKQPUNGCF
bland urinary sediment (that is, without red or to production of an abnormal
white blood cells) or who has (or has a family • Gout protein whose subsequent As genetic testing is not readily available to
member with) a kidney biopsy with compatible • Nocturia secretion is impaired all patients, efforts are underway to develop
• ESRD
histology. Other conditions must also be ruled alternative reliable methods to diagnose
out, including tubulointerstitial nephritis, uveitis ADTKD, including urinary tests. However, as
and Sjögren syndrome. For those without a family the disease is not glomerular (and, accordingly,
history, genetic testing can be pursued; however, • Gout proteins do not spill into the urine), developing
the benefit of having a definitive diagnosis may • ESRD biomarkers is challenging. Other areas
be outweighed by the reality that no specific of research include effective repurposing
treatments for ADTKD are available. HNF1B encodes HNF1β, a QH|CXCKNCDNGFTWIUVQVTGCVRCVKGPVUYKVJ
transcription factor with many
downstream targets; HNF1B ADTKD, developing of animal models to
9JGPCPCȭGEVGFIGPGKUKFGPVKȮGF mutations result in renal interstitial study disease mechanisms and determining
KVUJQWNFDGCFFGFCUCUWȰZVQVJG fibrosis, amongst other effects genotype–phenotype correlations.
VGTO#&6-&HQTGZCORNG#&6-&UMOD
KU|#&6-&ECWUGFD[OWVCVKQPUKPUMOD • Neurological SEC61A1OWVCVKQPUCȭGEV
features the translocation of newly
HNF1β • Abnormal synthesized polypeptides into
liver function
VJG'4RQVGPVKCNN[CȭGEVKPIVJG
• Gout
production of numerous proteins
• Early diabetes
MANAGEMENT • ESRD
• Anaemia
• Growth
Owing to the low prevalence of ADTKD, retardation
specific recommendations are based on limited • ESRD
evidence. Usually, patients with ADTKD are QUALITY OF LIFE
treated according to clinical guidelines for
CKD. This approach centres on, for example, As a dominantly inherited but slowly require transplantation or dialysis;
managing blood pressure, hyperuricaemia, progressing disorder, ADTKD has affected patients may have
anaemia, metabolic bone disease, acidosis, marked effects on quality of life experienced long-term disability passing the disease unknowingly to
electrolyte abnormalities and cardiovascular for all family members, even those and/or unemployment, leading to one’s offspring may occur. Anxiety
disease. Transplantation is the preferred option who are genetically unaffected. marked financial and emotional is a major issue in patients and
once patients have progressed to ESRD. Individuals may think they will effects; and feelings of guilt for families with ADTKD.

doi:10.1038/s41572-019-0119-7; Article citation ID: (2019) 5:61 Written by Mina Razzak; designed by Laura Marshall
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