Penetrance

Penetrance is age related. Thus, in individuals with childhood-onset disease, manifestations of ADTKD-REN, especially anemia, are evident early in life; and in individuals with adult-onset disease, manifestations (gout and chronic kidney disease) do not become evident until adulthood.

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

Diagnostic Criteria

Consensus clinical diagnostic criteria for autosomal dominant tubulointerstitial kidney disease due to REN pathogenic variants (ADTKD-REN) have been published (full text). Suggestive Findings ADTKD-REN should be suspected in individuals with the following clinical findings (grouped by age) and a family history consistent with autosomal dominant inheritance . Clinical Findings – Childhood/Adolescent-Onset Disease Low renin production (low to low-normal plasma renin and aldosterone levels associated with the following in most, but not all, individuals) manifesting as: • Blood pressure that is often borderline low, but usually asymptomatic • Hyperkalemia (serum potassium levels 5 mEq/L, sometimes as high as 6.5 mEq/L) in about 50% of individuals, often present from birth • Acidosis (serum bicarbonate levels between 15 and 24 mEq/L), often present from birth Hypoproliferative anemia in most affected children by age one year characterized by: • Low erythropoietin concentration • Low hemoglobin concentrations (usually 9-11 g/dL) • Low reticulocyte count relative to the hemoglobin concentration • Otherwise normal hematologic findings Hyperuricemia resulting from decreased renal excretion of uric acid: • Hyperuricemia (serum uric acid concentration 6 mg/dL) is present in 80% of affected individuals beginning in childhood. Usually, hyperuricemia in an individual with normal kidney function corresponds to a serum concentration of uric acid 1 SD above the normal value for age and sex. It is important to use age-related norms for serum urate . • Decreased fractional excretion of urinary uric acid in the vast majority of individuals with ADTKD-REN. See for reference ranges by age in individuals with normal kidney function. The fractional excretion of uric acid is usually 5% in adult men and 6% in adult women. The reduction of urate excretion can be detected in affected children with preserved renal function . Note: (1) The fractional excretion of urinary uric acid can be measured from a spot urine sample; however, a 24-hour urine collection is preferable. (2) Aspirin, diuretics, and nonsteroidal agents should be avoided during the collection. (3) Because the fractional excretion of uric acid rises above 5% as renal function worsens, this test is not sensitive in individuals who have an eGFR 70 mL/min. 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 – REN"

Differential Diagnosis

See for a diagnostic algorithm for inherited kidney disease. Table 5. Monogenic Kidney Diseases in the Differential Diagnosis of ADTKD-REN

Management Guidelines

Consensus management guidelines for autosomal dominant tubulointerstitial kidney disease due to pathogenic variants in REN (ADTKD-REN) have been published (full text).

Evaluations Following Initial Diagnosis

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

Table 6.

Recommended Evaluations Following Initial Diagnosis in Individuals with ADTKD-REN

System/Concern | Evaluation1

Anemia

| • Hemoglobin level

• In childhood/adolescent-onset ADTKD-REN: possibly erythropoietin level

Acidosis

| Serum bicarbonate (part of basic metabolic panel)

Hyperkalemia

| Serum potassium (part of basic metabolic panel)

Gout risk

| Serum urate

Hypotension

| In childhood/adolescent-onset ADTKD-REN: plasma renin/aldosterone level

Polyuria

| In childhood/adolescent-onset ADTKD-REN:

• Obtain history for enuresis excessive thirst or urination.

• 24-hr urine collection to quantify urine output

Kidney function

| Serum creatinine (part of basic metabolic panel)

Nephrology referral

Kidney structure

| Eval by kidney ultrasound

Genetic counseling

| Eval by genetics professionals2 to inform affected persons re nature, MOI, implications of ADTKD-REN to facilitate medical personal decision making

MOI = mode of inheritance

1. Applies to both presentations of ADTKD-REN except where indicated

2. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse

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

Clinical Guidance

Avoid use of the following:

• NSAIDs, especially in a person who is dehydrated or in a febrile child, as they can precipitate acute renal failure . The use of other analgesics/antipyretics should be considered.

• Angiotensin-converting enzyme inhibitors, which may not be beneficial in the treatment of CKD and could aggravate the underlying relative renin deficit

• Drugs known to be nephrotoxic

• The low-sodium diet typically prescribed in the treatment of CKD

Avoid the following, which may worsen hyperuricemia, leading to more frequent attacks of gout:

• Volume depletion, dehydration, and physical exertion under extreme conditions (e.g., when it is hot)

• High meat and seafood intake

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

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 – REN"

Surveillance Guidelines

Childhood/adolescent-onset disease. Monitor blood pressure, serum potassium, bicarbonate, creatinine, and hemoglobin at least every six months. Adult-onset disease. Monitor blood pressure, serum potassium, bicarbonate, creatinine, and hemoglobin every six to 12 months, depending on the level of kidney function.

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