Initial Workup for Suspected Renal Tubular Acidosis
Begin with blood gas analysis or venous total CO2 measurement to confirm metabolic acidosis, along with serum electrolytes including bicarbonate, chloride, potassium, and magnesium, plus urinary pH measurement—these are your first-line diagnostic tests. 1, 2
Essential Laboratory Testing
Blood Work
- Serum electrolytes including bicarbonate (to confirm metabolic acidosis with normal anion gap), chloride (hyperchloremic acidosis), potassium (hypokalemia in types 1 and 2, hyperkalemia in type 4), and magnesium 1, 3
- Blood gas analysis or venous total CO2 to assess severity of acidosis and confirm metabolic nature 1, 2
- Serum creatinine to evaluate renal function 1
- Serum calcium and phosphate for mineral metabolism assessment 1
- Parathyroid hormone (PTH) levels as part of mineral workup 1
Urine Studies
- Urinary pH measurement, particularly early morning pH >5.5 which suggests distal RTA 4
- Urinary glucose, amino acids, and protein to assess for Fanconi syndrome pattern 5
- Urinary calcium excretion and calcium:creatinine ratio to evaluate hypercalciuria risk for nephrocalcinosis 1
- Urinary phosphate and tubular reabsorption of phosphate 5
- Urinary citrate levels (typically low in distal RTA, increasing stone risk) 4
- Urine anion gap (Na+ + K+ - Cl-) to differentiate RTA types: positive gap suggests distal acidification defect, negative gap suggests GI or renal bicarbonate loss 6
Critical pitfall: A normal plasma bicarbonate does not exclude RTA—incomplete distal RTA can present with normal bicarbonate levels while complete dRTA shows bicarbonate <20 mmol/L. 4
Imaging Studies
- Renal ultrasound to evaluate for nephrocalcinosis, kidney stones, dilated tubules, echogenicity, enlarged kidneys, or cysts 5, 1
- Bone X-rays (wrist, chest) and densitometry for evidence of rachitic changes from hypophosphatemia or metabolic bone disease 5, 7
Repeat renal ultrasound every 12-24 months during follow-up to monitor for progression of nephrocalcinosis and stone formation. 1, 2
Cardiac Evaluation
- Electrocardiography to assess for QT interval prolongation and arrhythmias, as hypokalemia and hypomagnesemia can prolong QT interval and increase risk of life-threatening ventricular arrhythmias 1, 8
- Further cardiology workup (Holter monitoring, stress ECG) if patients report palpitations or syncope 1, 8
Specialized Testing
- Genetic testing should be considered for definitive diagnosis, particularly in pediatric cases or when inherited forms are suspected 1
- Urine diuretic screen if history is unclear, to exclude diuretic abuse as a mimic 8
Algorithmic Approach to Diagnosis
Step 1: Confirm normal anion gap hyperchloremic metabolic acidosis (plasma anion gap = Na+ - [Cl- + HCO3-] = 8-16 mEq/L) 6
Step 2: Check urine anion gap:
- Positive urine anion gap (Cl- < Na+ + K+) → suggests distal acidification defect 6
- Negative urine anion gap (Cl- >> Na+ + K+) → suggests GI or renal bicarbonate loss 6
Step 3: Assess plasma potassium:
- Hypokalemia → consider distal (type 1) or proximal (type 2) RTA 3, 9
- Hyperkalemia → consider type 4 RTA 3, 9
Step 4: Check urinary pH at low plasma bicarbonate:
Critical pitfall: Any patient with calcium phosphate kidney stones, low urinary citrate, and raised urinary pH (especially early morning pH >5.5) should be evaluated for underlying distal RTA, even if asymptomatic. 4
Monitoring After Diagnosis
- Infants and young children: every 3-6 months to ensure adequate metabolic control, growth, and psychomotor development 1, 2
- Older children with stable RTA: every 6-12 months 1, 2
- Adult patients: every 6-12 months 1, 2
- At each visit: monitor acid-base status (blood gas or venous total CO2), serum electrolytes (including bicarbonate, chloride, magnesium), and renal function 1, 2
Patients should be followed in specialized centers with experience in renal tubular disorders to optimize outcomes. 1, 8