Renal tubular acidosis: Varied aetiologies and clinical presentations: Three case reports

Table 1 Summary of the cases of renal tubular acidosis

Case	Age (years)/sex	Presenting complaint	Significant medical history	Lab findings	Imaging findings	Genetic testing	Diagnosis	Therapy
1	30/F	Pain, redness around right eye, swelling on cheek, mucopurulent discharge from nose, dental caries	Consanguineous parentage, developmental delay, severe intellectual impairment, recurrent fractures, hypokalemic periodic paresis since childhood	Hypokalemia, hyperchloremic metabolic acidosis, normal anion gap, alkaline urine pH	Osteopetrosis in radiographs of the skull and limbs, basal ganglia calcification in CT scan	Homozygous deletion variant in intron 3 of CA 2 gene	Proximal RTA (type 2)	Oral sodium bicarbonate and potassium citrate
2	56/M	Progressive weakness in limbs, femur neck fracture, thoracolumbar spine compression fractures	Proximal muscle weakness, inability to walk without support	Hypokalemia, elevated creatinine and urea, hyperchloremic metabolic acidosis, normal anion gap	Bilateral medullary nephrocalcinosis on kidney ultrasound	Heterozygous missense mutation in TRP6 gene suggestive of FSGS 2	Distal RTA (type 1)	Oral potassium citrate, right femur fracture fixation, denosumab
3	54/M	Quadriparesis, acute urinary retention	Recurrent episodes of hypokalemic quadriparesis	Hypokalemia, hyperchloremic metabolic acidosis, alkaline urine pH, Normal anion gap, Thyrotoxicosis, Elevated TSH receptor antibody, normal ANA, Elevated FBS and HbA1C	On ultrasound diffuse enlargement of thyroid with normal vascularity. Technetium 99 (99mTc) thyroid scintigraphy showed uniformly increased uptake in both lobes, 16.2% (normal 0.3%-3%), consistent with Graves’ disease	Nil	Distal RTA secondary to Graves’ disease	Oral sodium bicarbonate and potassium citrate for distal RTA. For Graves’ disease carbimazole, propranolol followed by radio-iodine ablation

CT: Computed tomography; CA 2: Carbonic anhydrase type 2; RTA: Renal tubular acidosis; FSGS: Focal segmental glomerulosclerosis; ANA: Antinuclear antibody; FBS: Fasting blood sugar; HbA1C: Hemoglobin A1C or glycated hemoglobin.

Table 2 Approach for diagnosis and treatment of renal tubular acidosis

Step	Description
Step 1: Clinical suspicion	Evaluate for symptoms: Growth retardation, non-healing rickets/osteomalacia, bone deformities, polyuria, nocturia, salt craving, muscle weakness
Step 2: Laboratory evaluation	Determination of arterial pH and anion gap. Check for non-anion gap metabolic acidosis
	Measure serum electrolytes (hypokalemia or hyperkalemia)
	Assess urine pH (< 5.5 or > 5.5)
	Calculate urine anion gap (Na + K) –Cl
	Measure serum bicarbonate levels
Step 3: Classification of RTA	Type 1 (distal) RTA
	Non-anion gap metabolic acidosis with urine pH > 5.5
	Hypokalemia, hypercalciuria, nephrocalcinosis, nephrolithiasis common
	Causes of distal RTA
	(1) Autoimmune causes (Sjogren’s, SLE, Graves’ disease, Primary biliary cholangitis, autoimmune hepatitis)
	(2) Genetic [sporadic gene mutations (SLC4A4, ATP6B1), Wilson’s disease, hereditary fructose intolerance, primary hyperoxaluria]
	(3) Drugs (amphotericin B, trimethoprim, analgesic abuse, toluene, amiloride, pentamidine)
	(4) Miscellaneous (sarcoidosis, amyloidosis, obstructive uropathy, interstitial nephritis, pyelonephritis, primary hyperparathyroidism, intravascular volume depletion of any cause, CKD of any cause, focal segmental glomerulosclerosis)
	Treatment: Alkali therapy [Bicarbonate supplement (2-3 mEq/kg/day)/Potassium Citrate]
	Thiazide diuretics (if hypercalciuria)
	Type 2 (Proximal RTA)
	Non-anion gap metabolic acidosis with urine pH < 5.5
	Associated with Fanconi’s syndrome
	Low molecular weight proteinuria
	Low serum phosphate levels
	Generalized aminoaciduria
	Glucosuria
	Causes of proximal RTA
	(1) Autoimmune (Sjogren’s, SLE)
	(2) Genetic [Sporadic gene mutations (SLC4A4, ATP6B1, ATP6NA1B), Wilson’s disease, Cystinosis, Lowe’s syndrome, Galactosemia]
	(3) Drugs (Amphotericin B, Trimethoprim, Analgesic abuse, toluene, amiloride, pentamidine, vanadium)
	(4) Miscellaneous causes (Amyloidosis, multiple myeloma, monoclonal gammopathy, light chain deposition disease, obstructive uropathy, nephrotic syndrome, medullary cystic kidney disease)
	Treatment
	High-dose alkali therapy (bicarbonate supplementation 5-20 mEq/kg/day)
	Phosphate supplementation
	Type 4 RTA (Hyporeninemic hypoaldosteronism)
	Non-anion gap metabolic acidosis
	Urine pH < 5.5
	Hyperkalemia
	Low serum aldosterone
	Low direct renin concentration
	Causes of type 4 RTA:
	Diabetic kidney disease
	CKD of any cause
	Drugs (NSAIDs, ACE inhibitors, ARBs, Heparin)
	Treatment
	Treat the underlying cause
	Dietary potassium restriction
	Fludrocortisone, if aldosterone deficiency
	Bicarbonate supplementation, if acidotic
	Type 3 RTA (Mixed RTA)
	Features of both distal and proximal RTA
	Causes (Rare, autosomal recessive osteopetrosis, carbonic anhydrase deficiency)
	Treatment: Similar to that of distal and proximal RTA with bicarbonate supplementation and electrolyte management
	Sometimes, features of both proximal and distal RTA may be present initially as a transient phenomenon, and on follow-up after treatment, one form may become predominant. This transient mixed presentation can occur in severe early cases of distal RTA, immature renal tubules in infants, or acquired conditions with widespread tubulopathy (autoimmune or toxic insults)
Step 4: Monitoring and follow-up	Regular monitoring of serum bicarbonate and potassium levels. Follow-up of nephrocalcinosis/nephrolithiasis, hypercalciuria, and renal functions. To adjust treatment doses based on clinical and biochemical parameters

RTA: Renal tubular acidosis; CKD: Chronic kidney disease; NSAID: Nonsteroidal anti-inflammatory drug; ACE: Angiotensin converting enzyme; ARB: Angiotensin receptor blocker.