• Clinical science

Renal tubular disorders

Summary

Renal tubular disorders are a very heterogeneous group of hereditary and acquired diseases that involve singular or complex dysfunctions of transporters and channels in the renal tubular system. The disorders may lead to fluid loss and abnormalities in electrolyte and acid-base homeostasis. Renal tubular acidosis (RTA) refers to normal anion gap (hyperchloremic) metabolic acidosis in the presence of normal or almost normal renal function. The various types of RTA include proximal tubular bicarbonate wasting (type II), distal tubular acid secretion (type I), and aldosterone deficiency/resistance (type IV). X-linked hypophosphatemic rickets, the most common form of hereditary hypophosphatemic rickets, is caused by phosphate wasting and presents with hypophosphatemia and symptoms related to rickets. Bartter syndrome, Liddle, and Gitelman syndrome are inherited disorders of tubular function that are characterized by hypokalemia and metabolic alkalosis. Renal tubular disorders are suspected when characteristic clinical features and/or laboratory findings are present. The diagnosis of hereditary conditions is usually confirmed by genetic testing. Treatment options vary depending on nature of the renal tubular disorder.

Renal tubular acidosis (RTA)

Overview of various forms of renal tubular acidosis
Type of renal tubular acidosis Type 1 RTA (distal RTA) Type 2 RTA (proximal RTA) Type 4 RTA (hyperkalemic RTA)
Incidence
  • Rare
  • Very rare
  • Common
Pathophysiology
  • Inability of the intercalated cells of the distal tubule to secrete H+
Serum potassium levels
Urine pH
  • > 5.5
  • < 5.5
  • < 5.5
Urine anion gap
  • Positive
  • Negative
  • Positive
Calcium excretion
  • Normal
  • Normal or ↓
Bone involvement
Nephrolithiasis
  • Usually present
  • Absent
  • Absent
Treatment
  • Alkali therapy with sodium bicarbonate or sodium citrate (Shohl's solution)
  • Alkali therapy with orally administered potassium citrate

Patients with uremic acidosis (metabolic acidosis due to renal failure) have a decreased glomerular filtration rate (↑ serum creatinine) and elevated anion-gap metabolic acidosis. On the other hand, patients with renal tubular acidosis have a relatively normal glomerular filtration rates and normal anion gap metabolic acidosis!

References:[1][2][3][4]

Type 1 renal tubular acidosis

References:[1][2][3]

Type 2 renal tubular acidosis

Isolated proximal RTA Fanconi syndrome
Pathophysiology
  • Only HCO3- reabsorption is impaired.
  • Impaired HCO3- reabsorption is associated with other defects of proximal renal tubular reabsorption (e.g., potassium, glucose, phosphate, and amino acid reabsorption).
Etiology

References:[1][2][3][4][5]

Type 4 renal tubular acidosis

References:[1][2][3]

X-linked hypophosphatemic rickets

References:[6][7]

Bartter syndrome

The effects of Bartter syndrome are similar to those of a loop diuretic!
References:[8][9]

Gitelman syndrome

The effects of Gitelman syndrome are similar to those of a thiazide diuretic!
References:[9]

Liddle syndrome