Renal calcification in children with renal tubular acidosis: What a paediatrician ‎should ‎know‎

Table 1 Comparison of different renal tubular acidosis types based on their etiology, pathogenesis, and key features.

Type of RTA		Type 1 RTA	Type 2 RTA	Type 3 RTA	Type 4 RTA
Prevalence		The most common type of RTA (1-2/100.000)	Less common than type 1 RTA (0.5/100.000)	Very rare	Slightly less common than type 1 RTA (1/100.000)
Location of defect		Distal nephron	Proximal nephron	Variable	Collecting duct
Etiology	Primary	Sporadic or hereditary (mutation of SLC4A1, H+-K+-ATPase, H+-ATPase)	Sporadic or hereditary (mutation of CA-IV, NHE-3, NBC-1)	Mutation in CA-II	PHA-1, PHA-2 (Gordon’s syndrome)
	Secondary	Autoimmune: Sjogren’s, SLE, RA, PBC; Nephrotoxins: Amphotercicn B, trimethoprim, lithium; Miscellaneous: Sarcoidosis, amyloidosis, obstructive uropathy	Autoimmune: Sjogren’s; Nephrotoxins: Tetracycline, topiramate, valproate, acetazolamide; Metabolic: Wilson’s disease, cystinosis, Lowe’s syndrome, galactosemia, chronic hypocalcemia; Hereditary fructose intolerance, tyrosinemia; Miscellaneous: Multiple myeloma, amyloidosis	Type 1 RTA with secondary proximal tubule dysfunction, type 2 RTA with secondary distal tubule dysfunction	Aldosterone deficiency or aldosterone resistance: Hypoaldosteronism, ACEIs, ARBs; Hyporeninemic hypoaldosteronism: Diabetes, sickle cell disease; Tubulointerstitial disease (eGFR: 20-50 ml/min); Drugs: Potassium sparing diuretics, NSAIDs, trimethoprim, pentamidine, cyclosporine, tacrolimus
Pathogenesis		Impaired hydrogen ion secretion & reduced bicarbonate reabsorption in the distal tubules	Impaired bicarbonate reabsorption in the proximal tubules	Impaired distal acidification and reduced bicarbonate reabsorption	Impaired hydrogen ion secretion and decreased potassium excretion due to reduced aldosterone activity
Degree of acidosis		Severe	Mild to moderate	Mild	Mild to moderate
Key features		Acidemia, hypobicarbonatemia, inability to acidify urine properly, and loss of bicarbonate ions in urine. Hypokalemia is common	Metabolic acidosis, loss of bicarbonate ions in urine, hypobicarbonatemia, electrolyte imbalances (e.g., hypokalemia, hypophosphatemia)	Metabolic acidosis, hypobicarbonatemia, variable features depending on the underlying systemic disease or medication	Metabolic acidosis, hyperkalemia, associated with hypoaldosteronism or resistance to aldosterone, potential electrolyte imbalances (e.g., hyponatremia, mild hyperchloremic acidosis)
Risk of renal calcification		High	Lower than type 1 RTA	Very low (variable)	Unknown

AE1: Anion exchanger 1; CA: Carbonic anhydrase; NHE-3: Sodium-hydrogen exchanger 3; NBC-1: Sodium-bicarbonate cotransporter 1; PHA: Pseudohypoaldosteronism; SLE: Systemic lupus erythematosus; RA: Rheumatoid arthritis; PBC: Primary biliary cirrhosis; ACE: Angiotensin converting enzyme; ARB: Angiotensin receptor blocker; RTA: Renal tubular acidosis.