What is ADTKD?
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is a set of kidney diseases that, collectively, are the second most common inherited cause of end-stage kidney disease (ESKD), with an estimated 75,000 - 100,000 patients in the US and one million worldwide.
There are three defining features of all subtypes of ADTKD:
- A parent also has/had kidney disease (“autosomal dominant inheritance”). If a parent has an ADTKD gene mutation, then there is a 50/50 chance they will pass it on to each of their children.
- Slowly progressing chronic kidney disease. Elevated serum creatinine and/or decreased estimated glomerular filtration rate (eGFR) at CKD Stage 2 or greater often presents in the 20’s, leading to the need for transplant or dialysis at an average age of about 45 years.
- Bland urinary sediment. With ADTKD, there is no blood or protein in the urine, ruling out glomerular disorders.
To date, researchers have discovered seven subtypes of ADTKD, named for the genes that are affected:
- ADTKD-UMOD
- ADKTD-MUC1
- ADTKD-REN
- ADTK-HNF1B
- ADTKD-SEC61A1
- ADTKD-DNAJB11
- APOA4
Currently, UMOD and MUC1 comprise the overwhelming majority of ADTKD cases.
What causes ADTKD?
- Mutations in affected genes lead to abnormal protein production.
- Instead of lining the surface of kidney cells as they should, these “misshapen” proteins accumulate inside the cells, causing cell death and leading to progressive kidney failure
Important to note: Loss of kidney function is irreversible. Once lost, it cannot be restored, even with medications or lifestyle changes.
What are the symptoms of ADTKD?
Almost 50% of ADTKD-UMOD patients experience hyperuricemia and gout beginning in the late teen years.
Otherwise, the only symptoms of ADTKD are elevated levels of creatinine and/or a decrease in the glomerular filtration rate (GFR).
How is ADTKD diagnosed?
A family history of kidney failure with no known cause should raise red flags among nephrologists that the cause may be genetic.
The most definitive test for ADTKD-MUC1 and ADTKD-UMOD is genetic testing. Kidney imaging and kidney biopsies do not help diagnose ADTKD.
How is ADTKD treated?
Currently, there are no available therapeutic treatments or cures for ADTKD.
However, researchers at The Broad Institute at MIT and Harvard have identified promising drug-like compounds that could HALT the devastating impacts of ADTKD-MUC1 and ADTKD-UMOD. The Broad Institute and its affiliate, NewCo, hope to conduct a clinical trial in the near future of these promising compounds.
What lifestyle changes can I make?
- Control blood pressure
- Eat a kidney-friendly diet commensurate with your stage of kidney disease
- Get regular exercise
- See your medical provider regularly
Are there complications to this disease?
Patients with ADTKD-UMOD are at increased risk of gout. Patients with ADTKD-MUC1 are at increased risk from COVID.
Additional Resources:
- For more information on ADTKD and genetic testing, please visit: rarekidney.org
- TED Talk by Dr. Anna Greka: The World’s Rarest Diseases – And How They Impact Everyone
- C-PATH Institute Webinar by Dr. Anthony Bleyer: Hidden in Plain Sight: Autosomal Dominant Tubulointerstitial Kidney Disease
