Clinical Guidance

The pathogenic variant is associated with less frequent gout and possibly a later age of onset of ESRD .

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

Penetrance

Penetrance appears to be complete, but age related. Some individuals (especially females) may not develop ESRD until the sixth or seventh decade.

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

Diagnostic Criteria

Consensus clinical diagnostic criteria for autosomal dominant tubulointerstitial kidney disease – UMOD (ADTKD-UMOD) have been published (full text). Suggestive Findings ADTKD-UMOD should be suspected in individuals with the following findings and family history. Autosomal dominant inheritance is a key finding in this disease with few distinctive clinical features. One should consider this diagnosis when both the patient and a parent have kidney disease, even if the parent's kidney disease is suspected of having another cause. Slowly progressive chronic kidney disease (CKD) is often present from childhood, as manifested with an estimated glomerular filtration rate (eGFR) 90 ml/min/1.73m2 . Bland urinary sediment without blood or protein is present in almost all individuals. Urinary protein is 250 mg/24 hours except when CKD is advanced (e.g., eGFR 40 mL/min/1.73m2). Hyperuricemia results from decreased renal excretion of uric acid and is found in almost all affected individuals. The fractional excretion of urate is 5% in most individuals with this disorder, but such a value can also be seen in healthy individuals . In children with the disorder, serum creatinine levels may be normal but elevated serum urate levels are usually present. Usually, hyperuricemia in an individual with normal kidney function corresponds to a serum concentration of uric acid 1 SD of the normal value for age and sex. It is important to use age-related norms for serum urate . Table 1. Serum Uric Acid Concentration in Individuals with Normal Renal Function Age | Serum Concentration (mg/dL) Males | Females

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

Differential Diagnosis

provides a diagnostic algorithm for inherited kidney disease. Hereditary glomerulonephritis. Affected individuals usually have proteinuria and/or hematuria. If blood or protein is present in the urine, consider hereditary forms of glomerulonephritis or hematuria (e.g., Alport syndrome). Rarely, individuals with ADTKD-UMOD have had proteinuria; however, this is uncharacteristic. Autosomal dominant polycystic kidney disease. If the urinary sediment is bland (i.e., with little blood or protein) in persons with kidney disease inherited in an autosomal dominant manner, one must exclude autosomal dominant polycystic kidney disease (ADPKD), in which a large number of cysts are seen on kidney ultrasound examination in affected individuals older than age 25 years. Other forms of ADTKD.

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

Management Guidelines

Consensus management guidelines for autosomal dominant tubulointerstitial kidney disease, UMOD (ADTKD-UMOD) have been published (full text).

Evaluations Following Initial Diagnosis

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

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with ADTKD-UMOD

System/Concern | Evaluation

Hypertension risk

| Measurement of blood pressure

Anemia

| Hemoglobin level

Kidney function

| Serum creatinine (part of basic metabolic panel)

Gout risk

| Serum urate concentration

Kidney structure

| Renal ultrasound exam

Nephrology referral

|

Genetic counseling

| By genetics professionals1 to inform affected persons re nature, MOI, implications of ADTKD-UMOD 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.

Hyperuricemia/Gout

Prevention of gout attacks with allopurinol should be considered in individuals with gout. With allopurinol treatment, serum uric acid concentration returns to normal and gout attacks can be entirely prevented. Lifelong therapy with allopurinol is required for future gout prevention.

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

Clinical Guidance

Avoid use of the following:

• Nonsteroidal anti-inflammatory drugs. NSAIDs are generally discouraged except for short-term treatment of gout or similar painful conditions in early CKD (prior to Stage 3 CKD). Chronic daily use should be avoided.

• Drugs known to be nephrotoxic

• The low sodium diet, which is typically prescribed in the treatment of CKD

• Volume depletion, dehydration, and physical exertion under extreme conditions (e.g., in hot weather), as these may worsen hyperuricemia, leading to more frequent attacks of gout

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

Therapies Under Investigation

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 – UMOD"

Surveillance Guidelines

Appropriate surveillance includes the following:

• Measurement of serum creatinine concentration at least annually in affected individuals, and more frequently in those with severe disease

• Measurement of serum uric acid concentration at least annually

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