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Disease Profile

Autosomal dominant tubulointerstitial kidney disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q61.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ADTKD; Autosomal dominant medullary cystic kidney disease; MCKD;

Categories

Kidney and Urinary Diseases

Summary

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of genetic kidney diseases that cause progressive loss of kidney function. Signs and symptoms of all forms of ADTKD include slowly worsening kidney disease (often becoming apparent by the teenage years) that ultimately results in end-stage kidney disease at some time between the ages of 20 and 70, depending on the genetic cause and severity. Urine exams of people with ADTKD show a bland urinary sediment (little blood or little or no protein). Kidney ultrasound examination is generally normal early in the disease course, but some people with ADTKD have cysts in the center of the kidneys (medullary cysts) that may be seen on an ultrasound.[1]

There are 3 known subtypes of ADTKD, which are classified based on their genetic causes and presence of additional features:[1][2][3]

  • UMOD-related autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) or uromodulin kidney disease (formerly known as UMOD-associated kidney disease, familial juvenile hyperuricemic nephropathy type 1, medullary cystic kidney disease type 2 (MCKD2), and uromodulin storage disease)caused by a mutation in the UMOD gene. This is the most common subtype. The age of onset varies but kidney problems are usually noted in adolescence,and may progress to end-stage renal disease (ESRD) between the fourth and seventh decades of life. High levels of uric acid in the blood (hyperuricemia) and gout (a form of arthritis), sometimes occur as early as the teenage years.
  • REN-related autosomal dominant tubulointerstitial kidney disease (ADTKD-REN) (previously known as "familial juvenile hyperuricemic nephropathy type 2") caused by a mutation in the REN gene. Kidney disease is usually present in childhood. Many people with this subtype also have anemia in childhood (even before kidney disease begins), low or low-normal blood pressure, mildly high levels of potassium in the blood (hyperkalemia), hyperuricemia and gout. 
  • MUC1-related autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1) or Mucin-1 kidney disease or MKD (formerly known as medullary cystic kidney disease type 1) caused by a mutation in the MUC1 gene. It is characterized by slowly progressive disease that leads to end-stage renal disease (ESRD) occurring at any age between 20 and 70 years. There are no other systemic features in addition to chronic kidney disease, although some develop gout in adulthood.

In some cases, the genetic cause of ADTKD in a family is not known. People with ADTKD of unknown cause typically do not have features in addition to chronic kidney disease (as is the case for MKD).[2]

Inheritance of ADTKD is autosomal dominant, as the name implies. Most people with ADTKD have a family history of "kidney disease" (if not a family history of ADTKD specifically) or some of the other symptoms. The diagnosis of ADTKD may be suspected based on family history, symptoms, and laboratory tests, and it can be confirmed by genetic testing.[1][2]

Treatment for kidney disease in people with ADTKD generally follows standard guidelines for chronic kidney disease and may involve kidney transplantation, which cures the disease.[4][5][6] The disease does not recur in the transplanted kidney.[1] Other treatments depend on the symptoms in each person. For example, gout may be treated with allopurinol.[1][2] High meat and seafood intake could worsen gout.[6] Treatment of anemia depends on whether it is causing symptoms.[1] Those with ADTKD-REN are advised to avoid a low-sodium diet and non-steroidal anti-inflammatory drugs.[1][5]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

      In-Depth Information

        References

        1. Bleyer A. Autosomal dominant tubulointerstitial kidney disease (medullary cystic kidney disease). UpToDate. Waltham, MA: UpToDate; Updated Dec. 5, 2018; https://www.uptodate.com/contents/autosomal-dominant-tubulointerstitial-kidney-disease-medullary-cystic-kidney-disease.
        2. Autosomal Dominant Tubulo-Interstitial Kidney Disease. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/autosomal-dominant-interstitial-kidney-disease/.
        3. REN-related kidney disease. Genetics Home Reference (GHR). January 2010; https://ghr.nlm.nih.gov/condition/ren-related-kidney-disease#genes.
        4. Bleyer AJ, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1-Related. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK153723/.
        5. Kmoch S, Zivna M, Bleyer AJ. Autosomal Dominant Tubulointerstitial Kidney Disease, REN-Related. GeneReviews. Updated Dec. 29, 2015; https://www.ncbi.nlm.nih.gov/books/NBK53700.
        6. Bleyer AJ, Hart PS, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease, UMOD-Related. GeneReviews. June 30, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1356/.