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 the relative's 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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