Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired bicarbonate resorption (type 2), or abnormal aldosterone production or response (type 4). (Type 3 is extremely rare and is not discussed.) Patients may be asymptomatic, display symptoms and signs of electrolyte derangements, or progress to chronic kidney disease. Diagnosis is based on characteristic changes in urine pH and electrolytes in response to provocative testing. Treatment corrects pH and electrolyte imbalances using alkaline agents, electrolytes, and, rarely, drugs.
RTA defines a class of disorders in which excretion of hydrogen ions or reabsorption of filtered bicarbonate is impaired, leading to a chronic metabolic acidosis with a normal anion gap. Hyperchloremia is usually present, and secondary derangements may involve other electrolytes, such as potassium (frequently) and calcium (rarely—see table Some Features of Different Types of Renal Tubular Acidosis).
Chronic RTA is often associated with structural damage to renal tubules and may progress to chronic kidney disease.
Type 1 (distal) RTA
Type 1 is impairment in hydrogen ion secretion in the distal tubule, resulting in a persistently high urine pH (> 5.5) and systemic acidosis. Plasma bicarbonate is frequently < 15 mEq/L (15 mmol/L), and hypokalemia, hypercalciuria, and decreased citrate excretion are often present. Hypercalciuria is the primary abnormality in some familial cases, with calcium-induced tubulointerstitial damage causing distal RTA. Nephrocalcinosis and nephrolithiasis are possible complications of hypercalciuria and hypocitraturia if urine is relatively alkaline.
This syndrome is rare. Sporadic cases occur most often in adults and may be primary (nearly always in women) or secondary. Familial cases usually first manifest in childhood and are most often autosomal dominant. Secondary type 1 RTA may result from drugs, kidney transplantation, or various disorders:
Autoimmune disease with hypergammaglobulinemia, particularly Sjögren syndrome or rheumatoid arthritis
Nephrocalcinosis
Chronic obstructive uropathy
Potassium level may be high in patients with chronic obstructive uropathy or sickle cell anemia.
Type 2 (proximal) RTA
Type 2 is impairment in bicarbonate resorption in the proximal tubules, producing a urine pH > 7 if plasma bicarbonate concentration is normal, and a urine pH < 5.5 if plasma bicarbonate concentration is already depleted as a result of ongoing losses.
Type 2 RTA is very rare and most often occurs in patients who have one of the following:
kidney transplantation, heavy metal exposure, and other inherited diseases (eg, fructose intolerance, Wilson disease, oculocerebrorenal syndrome [Lowe syndrome], cystinosis).
Type 4 (generalized) RTA
Type 4 results from aldosterone deficiency or unresponsiveness of the distal tubule to aldosterone. Because aldosterone triggers sodium resorption in exchange for potassium and hydrogen, there is reduced potassium excretion, causing hyperkalemia and reduced acid excretion. Hyperkalemia may decrease ammonia excretion, contributing to metabolic acidosis. Urine pH is usually appropriate for serum pH (usually < 5.5 when there is serum acidosis). Plasma bicarbonate is usually > 17 mEq/L (17 mmol/L).
This disorder is the most common type of RTA. It typically occurs sporadically secondary to impairment in the renin-aldosterone-renal tubule axis (hyporeninemic hypoaldosteronism), which occurs in patients with the following:
Other factors that can contribute to type 4 RTA include the following:
ACE inhibitor use
Aldosterone synthase type I or II deficiency
Chronic kidney disease, usually due to diabetic nephropathy or chronic interstitial nephritis
Congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency
Critical illness
HIV nephropathy (due, possibly in part, to infection with Mycobacterium avium complex or cytomegalovirus)
Interstitial renal damage (eg, due to systemic lupus erythematosus, obstructive uropathy, or sickle cell disease)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Primary adrenal insufficiency
Pseudohypoaldosteronism (type I or II)
Volume expansion (eg, in acute glomerulonephritis or chronic kidney disease)
Symptoms and Signs of RTA
RTA is usually asymptomatic. Severe electrolyte disturbances are rare but can be life threatening.
Nephrolithiasis and nephrocalcinosis are possible, particularly with type 1 RTA.
Signs of extracellular fluid volume depletion may develop from urinary water loss accompanying electrolyte excretion in type 2 RTA.
People with type 1 or type 2 RTA may show symptoms and signs of hypokalemia, including muscle weakness, hyporeflexia, and paralysis. Bony involvement (eg, bone pain and osteomalacia in adults and rickets in children) may occur in type 2 and sometimes in type 1 RTA.
Type 4 RTA is usually asymptomatic with only mild acidosis, but cardiac arrhythmias or paralysis may develop if hyperkalemia is severe.
Diagnosis of RTA
Suspected in patients with metabolic acidosis with normal anion gap or with unexplained hyperkalemia
Serum and urine pH, electrolyte levels, and osmolalities
Often, testing after stimulation (eg, with ammonium chloride, bicarbonate, or a loop diuretic)
RTA is suspected in any patient with unexplained metabolic acidosis (low plasma bicarbonate and low blood pH) with normal anion gap. Type 4 RTA should be suspected in patients who have persistent hyperkalemia with no obvious cause, such as potassium supplements, potassium-sparing diuretics, or chronic kidney disease
Type 1 RTA is confirmed by a urine pH that remains > 5.5 during systemic acidosis. The acidosis may occur spontaneously or be induced by an acid load test (administration of ammonium chloride 100 mg/kg orally). Normal kidneys reduce urine pH to < 5.2 within 6 hours of acidosis.
Type 2 RTA> 15%. Because IV bicarbonate can contribute to hypokalemia, potassium supplements should be given in adequate amounts before infusion.
Type 4 RTA is confirmed by a history of a condition that could be associated with type 4 RTA, chronically elevated potassium, and normal or mildly decreased bicarbonate. In most cases plasma renin activity is low, aldosterone concentration is low, and cortisol is normal.
Treatment of RTA
Varies by type
Often alkali therapy
Treatment of concomitant abnormalities related to potassium, calcium, and phosphate metabolism
Treatment consists of correction of pH and electrolyte balance with alkali therapy. Failure to treat RTA in children slows growth.
hypokalemia is present or, because sodium increases calcium excretion, when calcium calculi are present.
Type 1 RTA
Type 2 RTA
Type 4 RTA
Key Points
Renal tubular acidosis is a class of disorders in which excretion of hydrogen ions or reabsorption of filtered bicarbonate is impaired, leading to a chronic metabolic acidosis with a normal anion gap.
RTA is usually due to abnormal aldosterone production or response (type 4), or less often, due to impaired hydrogen ion excretion (type 1) or impaired bicarbonate resorption (type 2).
Consider RTA if patients have metabolic acidosis with a normal anion gap or unexplained hyperkalemia
Check ABG and serum electrolytes, BUN, and creatinine, and urine pH.
Do other testing to confirm type of RTA (eg, acid load test for type 1, bicarbonate infusion for type 2).
Treat using alkali therapy and measures to correct low serum potassium in type 2 and sometimes type 1 RTA , and using potassium restriction or potassium-wasting diuretics in type 4 RTA; give other electrolytes as needed.
