Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1

Clinical Characteristics: Autosomal dominant tubulointerstitial kidney disease – MUC1 (ADTKD- MUC1 ) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations.
Diagnosis/testing: The diagnosis of ADTKD- MUC1 is established in a proband with suggestive clinical findings and molecular genetic testing that reveals a heterozygous pathogenic variant in MUC1 that results in the creation of a specific frameshift protein (MUC1fs) responsible for the pathogenic changes in this disorder.
Management: Treatment of manifestations : Treatment follows standard guidelines for chronic kidney disease – based on the level of the serum creatinine and the estimated glomerular filtration rate (eGFR) – and its sequelae, which can include hypertension, anemia, and gout. Affected individuals are encouraged to prepare for kidney transplantation, the definitive treatment of ADTKD -MUC1 , by staying in optimal health (e.g., by exercising, avoiding obesity and tobacco usage, and maintaining strict control of hypertension, dyslipidemia, and other cardiovascular risk factors). Kidney transplantation is curative; the outcome is excellent. Surveillance : Measurement of hemoglobin, serum concentrations of uric acid and creatinine and blood pressure annually prior to entering CKD Stage 3. Thereafter, follow up is determined by the treating nephrologist. Agents/circumstances to avoid : Affected individuals should follow general recommendations for chronic kidney disease. Pregnancy management : The use of ACE inhibitors should be avoided during pregnancy, as they can result in fetal damage and death. Women who are pregnant, planning a pregnancy, or not actively avoiding pregnancy should be transitioned to another antihypertensive medication. Allopurinol therapy should be stopped during pregnancy, if possible. Evaluation of relatives at risk : For early diagnosis and treatment: It is appropriate to identify as early as possible apparently asymptomatic at-risk adult relatives who have the familial MUC1 variant in order to monitor their serum creatinine levels and promptly initiate treatment and awareness of agents/circumstances to avoid. For kidney donation: Any relative who is a potential kidney donor should undergo molecular genetic testing to clarify his/her genetic status so that only those who do not have the familial MUC1 pathogenic variant are evaluated further.
Genetic Counseling: ADTKD- MUC1 is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% chance of inheriting the MUC1 pathogenic variant. Prenatal testing for MUC1 pathogenic variants is not available in the US at this time.
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