Diagnostic Criteria

A clinical diagnosis for hereditary distal renal tubular acidosis (dRTA) can be established in an individual with early-onset dRTA if secondary causes of dRTA (e.g., autoimmune diseases or medications) can be excluded.

Suggestive Findings

Hereditary dRTA should be suspected in probands with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

• Poor weight gain and growth deficiency in childhood

• Sensorineural hearing loss

• Symptoms of hypokalemia, including muscle weakness and muscle cramps

• Bone manifestations (10%-23%): osteomalacia (in adults), refractory rickets (in children), fractures, bone pain

• Exclusion of systemic diseases (e.g., autoimmune disorders) and medications causing dRTA

Laboratory findings

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"

Differential Diagnosis

Metabolic acidosis with normal anion gap and hypokalemia is also observed in disorders causing loss of bicarbonate either from the proximal tubule or the gastrointestinal tract.

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"

Management Guidelines

The European Rare Kidney Disease Reference Network and the Inherited Kidney Diseases Working Group of the European Society for Paediatric Nephrology published clinical practice guidelines for the management of individuals with distal renal tubular acidosis (dRTA) . This chapter summarizes most of these recommendations, based on expert consensus opinion, as well as the authors' personal experience managing individuals with hereditary dRTA.

Evaluations Following Initial Diagnosis

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

Table 4.

Hereditary Distal Renal Tubular Acidosis: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Renal

| Venous blood gas or total plasma CO2 | • Eval of acid-base equilibrium

• Sample to be drawn in fasting conditions immediately before scheduled dose of alkali to assess effectiveness of therapy

Serum creatinine, urea, sodium, potassium, chloride | • Evaluate GFR

• Assess hypokalemia hydration status.

Serum calcium, phosphate, ALP, magnesium | Assess for hypocalcemia, biochemical evidence of rickets, hypophosphatemia.

Uric acid, albumin | Assess for assoc tubular dysfunction.

Urinalysis | Detection of proteinuria, hematuria, leukocyturia

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"

Clinical Guidance

Potassium-sparing diuretics should be used with caution or avoided altogether.

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"

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.

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 7.

Hereditary Distal Renal Tubular Acidosis: Recommended Surveillance

System/Concern | Evaluation | Comment

Renal

| Venous blood gas | • In rapidly growing persons (infants young children): at least every 3-4 mos once blood pH is normalized w/o evidence of respiratory compensation

• In older children: every 6 mos

• In adults: annually

• Sample to be drawn in fasting conditions immediately before scheduled dose of alkali

Serum creatinine, urea, sodium, potassium, chloride, calcium, phosphate, alkaline phosphatase, albumin | • In rapidly growing persons (infants young children): at least every 3-4 mos once adequate control is achieved

• In stable older children adults: every 6-12 mos

Urinalysis urine creatinine, sodium, potassium, calcium, citrate | • Annually

• More frequently when adjusting treatment

Renal ultrasound | Annual eval for nephrocalcinosis, urolithiasis, cysts in asymptomatic persons

Growth

| • Measure length/height weight.

• Calculate BMI.

| • In infants: at least every 3 mos

• In older children: at least every 6 mos until achievement of final height

Skeletal

| Bone densitometry | No consensus exists on benefit of follow-up bone densitometry, although it may be reasonable to measure bone densitometry in adults every 2-3 years.

Source: GeneReviews — "Hereditary Distal Renal Tubular Acidosis"