For physicians

“Every nephrologist cares for a patient with ADTKD."​

- Dr. Anthony J. Bleyer, Nephrologist, Wake Forest University School of Medicine

Up to 10% of all CKD patients in the U.S. – as many as 3.7 million people – are estimated to have a genetic mutation that causes their disease. This staggering number includes an estimated 25% of dialysis patients who, along with their nephrologists, are in the dark about the cause of their kidney failure. This lack of knowledge contributes to non-diagnosis.

An estimated 75,000 to 100,000 of these patients have Autosomal Dominant Tubulointerstitial Kidney Diseases (ADTKD), making it the 2nd most prevalent genetic kidney disease in the US (after PKD).

ABOUT ADTKD

​In ADTKD, mutations in certain genes lead to abnormal protein production that damages the kidney’s tubulointerstitium, causing progressive decline in kidney functioning until dialysis or transplantation is required. 

ADTKD includes at least seven different subtypes, named for the genes that are affected: ADTKD-UMOD, ADKTD-MUC1, ADTKD-REN, ADTK-HNF1B, ADTKD-SEC61A1, ADTKD-DNAJB11, and most recently discovered, APOA4.

ADTKD-MUC1 and ADTKD-UMOD comprise the majority of cases. 

Prior to the discovery of the UMOD gene mutation in 2001, ADTKD-UMOD was known as familial juvenile hyperuricemic nephropathy type 1 (FJHN1), uromodulin-associated kidney disease (UMOD-associated kidney disease), or medullary cystic kidney disease type 2. Prior to the discovery of the MUC1 gene mutation in 2013, ADTKD-MUC1 was known as medullary cystic kidney disease type 1.

WHAT ARE THE DEFINING FEATURES OF MUC1 and umod?

There are three defining features of all subtypes of ADTKD:​

1. Autosomal dominant inheritance. All subtypes of ADTKD have an autosomal dominant inheritance. If a parent has an ADTKD gene mutation, there is a 50/50 chance they will pass it on to each of their children (regardless of the child’s gender). 

2. Slow progression. The decline in kidney functioning occurs over many years. Many people may not even know they have kidney disease until routine blood work detects elevated creatinine or declining glomerular filtration rate.  The rate of decline can vary widely – both across families and for individuals within the same family – with some experiencing end-stage renal failure in their 20s, while others do not experience kidney failure until their 70s or 80s.

3. Bland urinary sediment. With ADTKD, there is no blood and rarely is there protein in the urine, ruling out glomerular disorders.

HOW IS ADTKD DIAGNOSED?

ADTKD may be suspected if a patient has at least one of the defining features listed above. 

In addition, ADTKD-UMOD is usually first noticed in the teen years due to hyperuricemia. Gout occurs in the teenage years in about 15% of affected individuals and develops in 55% of affected individuals over time. 

With ADTKD-MUC1, chronic kidney disease rarely begins before age 20, and clinical manifestations of ADTKD-MUC1 – such as hypertension, anemia, and gout – typically occur later in the disease’s progression and are related to a decline in eGFR or an increase in creatinine.

The most definitive test for ADTKD-MUC1 and ADTKD-UMOD is genetic testing. A kidney biopsy does not help diagnose ADTKD.

WHAT TREATMENTS ARE AVAILABLE FOR ADTKD?

Treatment of ADTKD focuses mainly on managing the symptoms associated with each subtype and adopting healthy behaviors - such as controlling blood pressure, eating a kidney-friendly diet, and getting regular exercise. Currently, there are no available therapeutic treatments or cures for ADTKD. 

However, researchers at The Broad Institute at MIT and Harvard are making significant progress. They 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 of these promising compounds in the near future.

RKDF’S GOAL

RKDF seeks to find and refer 300 kidney patients to the Rare Inherited Kidney Disease Research Team for genetic testing and possible enrollment in the International ADTKD Registry in preparation for future clinical trials.​

Every patient who undergoes genetic testing brings our research partners one step closer to achieving this goal.

Our ultimate goal is to support our research partners in finding a cure for ADTKD.

YOU CAN HELP: JOIN THE RARE KIDNEY DISEASE CLINICIAN COUNCIL

RKDF has established the Rare Kidney Disease Clinician Council to advise RKDF on how best to craft our message of HOPE to nephrologists around a promising treatment for HALTING ADTKD and to amplify this message with their colleagues and professional associations.

Outcomes expected from the Rare Kidney Disease Clinician Council are:

• An increase in the number of nephrologists who refer their patients for genetic testing  

• An increase in the number of patients referred to RKDF by their nephrologists 

• An increase in the number of patients RKDF refers to the ADTKD International Registry originating from nephrologist referrals 

• Clinician council members share valuable insights and recommendations with leading ADTKD physician-researchers, contributing to developments in the ADTKD field

By joining the Clinician Council, you can make a real difference in the lives of your patients and kidney patients around the world.

For more information and to join the Clinician Council, contact us using the form below.