Clinical characteristics: Autosomal dominant tubulointerstitial kidney disease – UMOD (ADTKD-UMOD) is characterized by normal urinalysis and slowly progressive chronic kidney disease (CKD), usually first noted in the teen years and progressing to end-stage renal disease (ESRD) between the third and seventh decades. Hyperuricemia is often present from an early age, and gout (resulting from reduced kidney excretion of uric acid) occurs in the teenage years in about 8% of affected individuals and develops in 55% of affected individuals over time.

Diagnosis/testing: The diagnosis of ADTKD-UMOD is established in a proband with suggestive findings and a heterozygous pathogenic variant in UMOD identified by molecular genetic testing.

Management: Treatment of manifestations: With allopurinol treatment, serum uric acid concentration returns to normal and gout attacks can be entirely prevented. Lifelong therapy with allopurinol is required for future gout prevention. Referral to a nephrologist to monitor kidney function; evaluate for manifestations of CKD, and prepare for renal replacement therapy when ESRD occurs. Renal replacement therapies such as hemodialysis and peritoneal dialysis replace kidney function but are associated with potential complications; kidney transplantation is curative.

Surveillance: Measurement of serum creatinine concentration at least annually in affected individuals, and more frequently in those with severe disease; measurement of serum uric acid concentration at least annually.

Agents/circumstances to avoid: Drugs known to be nephrotoxic; volume depletion and dehydration. Nonsteroidal anti-inflammatory drugs are generally discouraged but could be used for short-term administration for treatment of gout or similar painful conditions in early CKD (prior to Stage 3 CKD). Chronic daily use should be avoided.

Evaluation of relatives at risk: Asymptomatic at-risk relatives younger than age 18 years from a family with ADTKD-UMOD with an early age of onset of gout may benefit from testing for the familial UMOD pathogenic variant so that those with the variant can initiate treatment that would prevent gout.

It is appropriate to clarify the genetic status of apparently asymptomatic at-risk adult relatives in order to identify those with the familial UMOD pathogenic variant (and thus, at risk for CKD) who would be benefit from routine surveillance and awareness of agents/circumstances to avoid.

Any relative who is a potential kidney donor should be tested for the familial UMOD pathogenic variant so that only those without the variant are evaluated further for kidney donation.

Pregnancy management: The use of angiotensin-converting enzyme inhibitors even in early pregnancy can result in fetal damage and death. Use of allopurinol during pregnancy should be avoided.

Genetic counseling: ADTKD-UMOD is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% chance of inheriting the UMOD pathogenic variant. Once the UMOD pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at risk and preimplantation genetic testing are possible.