Diagnostic Criteria

Autosomal dominant tubulointerstitial kidney disease – MUC1 (ADTKD-MUC1) is caused by a heterozygous MUC1 pathogenic variant which results in the creation of a specific frameshift protein (MUC1fs) responsible for slowly progressive chronic kidney disease, the sole manifestation of this disorder. Consensus clinical diagnostic criteria for ADTKD-MUC1 have been published (full text).

Suggestive Findings

ADTKD-MUC1 should be suspected in individuals with the following clinical, laboratory and imaging findings, and family history.

Clinical Findings

Slowly progressive chronic tubulointerstitial kidney disease, evident as a slowly rising serum creatinine in the absence of hematuria and protein, is the sole clinical manifestation of this disorder; all other findings are secondary.

Laboratory Findings

Th...

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"

Differential Diagnosis

See for the recommended testing strategy for the diagnosis of inherited kidney disease.

Urinalysis

If blood and protein are present, consider evaluation for inherited glomerulonephritis. If the urine sediment is bland (trace or no blood and protein 500 mg/24 h), obtain a family history to determine the likely inheritance pattern. If autosomal recessive (i.e., only sibs are affected), consider autosomal recessive polycystic kidney disease or the group of disorders termed "nephronophthisis" .

Renal Imaging

Renal imaging should always be performed. Ultrasound examination is typically performed first. If numerous cortical and medullary cysts and enlarged kidneys are present, consider autosomal dominant polycystic kidney disease (ADPKD).

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"

Management Guidelines

Consensus management guidelines for autosomal dominant tubulointerstitial kidney disease caused by pathogenic variants in MUC1 (ADTKD-MUC1) have been published (full text). At present, there are no specific therapies for ADTKD-MUC1, and affected individuals should receive symptomatic care appropriate for their stage of chronic kidney disease.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with ADTKD-MUC1, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with ADTKD-MUC1

System/Concern | Evaluation

Hypertension risk

| Measurement of blood pressure

Anemia

| Hemoglobin level

Acidosis

| Serum bicarbonate (part of basic metabolic panel)

Hyperkalemia

| Serum potassium (part of basic metabolic panel)

Kidney function

| Serum creatinine (part of basic metabolic panel)

Gout risk

| Serum urate concentration

Kidney structure

| Renal ultrasound exam

Kidney function

| Nephrology referral

Genetic counseling

| By genetics professionals1 to inform affected persons re nature, MOI, implications of ADTKD-MUC1 in order to facilitate medical personal decision making

MOI = mode of inheritance

1. Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

Care by a nephrologist is recommended. Treatment follows standard guidelines for chronic kidney disease – based on the le...

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"

Clinical Guidance

Affected individuals should follow general recommendations for chronic kidney disease.

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"

Therapies Under Investigation

Of note, basic science and animal studies have identified a potential therapy for the small molecule BRD4780, which was found to clear MUC1 frameshift protein deposits in cells in culture, organoids, and a mouse model of ADTKD-MUC1. This compound is anticipated to enter clinical trials within the next two to five years . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"

Surveillance Guidelines

Monitor the following annually, starting at the time of diagnosis and continuing until chronic kidney disease (CKD) Stage 3:

• Hemoglobin concentration

• Serum concentrations of uric acid and creatinine

• Blood pressure

After CKD Stage 3, follow up is determined by the treating nephrologist.

Source: GeneReviews — "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1"