Renal tubular acidosis

Renal tubular acidosis (RTA) refers to defects in the renal tubular transport of hydrogen ions, bicarbonate ions, or both, in the kidneys resulting in a normal anion gap metabolic acidosis.

Epidemiology

The exact prevalence of renal tubular acidosis is unknown but the entity is probably under-recognized. However, it is known that primary forms are rarer than acquired forms .

Clinical presentation

Renal tubular acidosis produces a normal anion gap metabolic acidosis and hyperchloremia. It should be suspected in patients with this pattern of acidosis and electrolyte disturbance and the absence of gastrointestinal bicarbonate loss.

Patients may have a relatively normal renal function and glomerular filtration rate . Clinical features otherwise depend on the type of renal tubular acidosis:

• type 1: hypercalciuria, polyuria, impaired growth, nephrocalcinosis, urolithiasis and hypokalemia
• type 2: rickets and osteomalacia are not usually seen unless hypophosphatemia is also present (e.g. Fanconi syndrome), nephrocalcinosis and urolithiasis are uncommon overall
• type 4: nephrocalcinosis and nephrolithiasis are generally absent

Pathology

Renal acid-base homeostasis is achieved primarily through two processes: either reabsorption of bicarbonate ions in the proximal tubule or urinary acidification in the distal tubule.

Renal tubular acidosis has been classified into four types :

• type 1 renal tubular acidosis (distal renal tubular acidosis):
  • caused by impaired distal tubal acidification, and defined as the inability to acidify urine (i.e. urinary pH becomes >5.5) under the stimulus of a systemic academia
  • impaired secretion of NH4 ions occurs secondary to this
  • bicarbonate ion resorption is essentially normal
  • causes:
    • primary causes: idiopathic or genetic
    • secondary: autoimmune disease (e.g. Sjögren syndrome (most common), SLE), genetic disease (e.g. sickle cell disease), drugs (eg. lithium, amphotericin B), calcium disorders (e.g. primary hyperparathyroidism), or renal disease (e.g. medullary sponge kidney).
• type 2 renal tubular acidosis (proximal renal tubular acidosis): 
  • caused by an impaired ability to reabsorb bicarbonate in the proximal tubule, so the majority is lost and bicarbonaturia occurs resulting in a metabolic acidosis
  • causes:
    • primary: e.g. idiopathic and hereditary forms or as part of Fanconi syndrome
    • secondary: proteinaemic syndromes (e.g. multiple myeloma, amyloidosis), drugs (e.g. acetazolamide) 
• type 4 renal tubular acidosis (hyperkalemic renal tubular acidosis): 
  • defined as an ability to normally acidify the urine (pH <5.5) after a systemic acid load but with defects in the ability to produce and secrete ammonia ions
  • generally secondary to hypoaldosteronism
    • decreased renin and decreased aldosterone: diabetic nephropathy (classic), NSAIDs
    • normal renin and decreased aldosterone: ACE inhibitors, angiotensin receptor blockers
    • decreased response to aldosterone: spironolactone, trimethoprim, tacrolimus
• a fourth type (type 3) of renal tubular acidosis is also described where patients share features of both type 1 and type 2 renal tubular acidosis
  • it is now referred to as a sub-type of type 1 disease

Radiographic features

Radiographic signs are generally only seen in those with type 1 renal tubular acidosis or those with chronic kidney disease from another type of renal tubular acidosis . Signs of the underlying disorder causing secondary forms of renal tubular acidosis may also be visible (eg. medullary cystic disease).

Plain radiograph

The changes seen on radiograph relate in calcium resorption from bone or deposition in the kidneys. Nephrocalcinosis and nephrolithiasis, as well as rickets in children and osteomalacia in adults, may be seen in type 1 disease. Osteopenia may be seen in type 4 disease .

Ultrasound

Nephrocalcinosis, if present, is also often visible on ultrasound.

Treatment and prognosis

The treatment of renal tubular acidosis involves correcting the underlying cause or ceasing the offending drug in secondary forms of the disorder, as well as alkali supplementation in the form of either bicarbonate or citrate. Treatment should begin as early as possible to stop progression to nephrocalcinosis and chronic kidney disease .