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Renal Tubular Acidosis (RTA)

by James I. McMillan, MD

Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired HCO 3 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 HCO 3 is impaired, leading to a chronic metabolic acidosis (see Metabolic Acidosis) with a normal anion gap. Hyperchloremia is usually present, and secondary derangements may involve other electrolytes, such as K (frequently) and Ca (rarely— 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 (see Chronic Kidney Disease).

Some Features of Different Types of Renal Tubular Acidosis*


Type 1

Type 2

Type 4



Very rare



Impaired H + excretion

Impaired HCO 3 resorption

Decrease in aldosterone secretion or activity

Plasma HCO 3 (mEq/L)

Usually < 15, often < 10

Usually 12–20

Usually > 17

Plasma K

Usually low but tends to normalize with alkalinization

Usually low and decreased further by alkalinization


Urine pH

> 5.5

> 7 if plasma HCO 3 is normal

< 5.5 if plasma HCO 3 is depleted (eg, < 15 mEq/L)

< 5.5

*Type 3 is very rare.

H + = hydrogen ion.

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 HCO 3 is usually < 15 mEq/L, and hypokalemia, hypercalciuria, and decreased citrate excretion are often present. Hypercalciuria is the primary abnormality in some familial cases, with Ca-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 various disorders, drugs, or kidney transplantation:

  • Autoimmune disease with hypergammaglobulinemia, particularly Sjögren syndrome or RA

  • Kidney transplantation

  • Nephrocalcinosis

  • Medullary sponge kidney

  • Chronic obstructive uropathy

  • Drugs (mainly amphotericin B, ifosfamide, and lithium)

  • Cirrhosis

  • Sickle cell anemia

K level may be high in patients with chronic obstructive uropathy or sickle cell anemia.

Type 2 (proximal) RTA

Type 2 is impairment in HCO 3 resorption in the proximal tubules, producing a urine pH > 7 if plasma HCO 3 concentration is normal, and a urine pH < 5.5 if plasma HCO 3 concentration is already depleted as a result of ongoing losses. This syndrome may occur as part of a generalized dysfunction of proximal tubules and patients can have increased urinary excretion of glucose, uric acid, phosphate, amino acids, citrate, Ca, K, and protein. Osteomalacia or osteopenia (including rickets in children) may develop. Mechanisms may include hypercalciuria, hyperphosphaturia, alterations in vitamin D metabolism, and secondary hyperparathyroidism. Type 2 RTA is very rare and most often occurs in patients who have one of the following:

  • Fanconi syndrome

  • Light chain nephropathy due to multiple myeloma

  • Various drug exposures (usually acetazolamide, sulfonamides, ifosfamide, outdated tetracycline, or streptozocin)

It sometimes has other etiologies, including vitamin D deficiency, chronic hypocalcemia with secondary hyperparathyroidism, 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 Na resorption in exchange for K and hydrogen, there is reduced K 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 HCO 3 is usually > 17 mEq/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:

  • Diabetic nephropathy

  • Chronic interstitial nephritis

Other factors that can contribute to type 4 RTA include the following:

  • ACE inhibitor use

  • Aldosterone synthase type I or II deficiency

  • Angiotensin II receptor blocker use

  • Chronic kidney disease, usually due to diabetic nephropathy or chronic interstitial nephritis

  • Congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency

  • Critical illness

  • Cyclosporine use

  • Heparin use (including low molecular weight heparins)

  • HIV nephropathy (due, possibly in part, to infection with Mycobacterium avium complex or cytomegalovirus)

  • Interstitial renal damage (eg, due to SLE, obstructive uropathy, or sickle cell disease)

  • K-sparing diuretics (eg, amiloride, eplerenone, spironolactone, triamterene)

  • NSAID use

  • Obstructive uropathy

  • Other drugs (eg, pentamidine, trimethoprim)

  • Primary adrenal insufficiency

  • Pseudohypoaldosteronism (type I or II)

  • Volume expansion (eg, in acute glomerulonephritis or chronic kidney disease)

Symptoms and Signs

RTA is usually asymptomatic. However, bony involvement (eg, bone pain and osteomalacia in adults and rickets in children) may occur in type 2 and sometimes in type 1 RTA. Nephrolithiasis and nephrocalcinosis are possible, particularly with type 1 RTA.

Severe electrolyte disturbances are rare but can be life threatening. People with type 1 or type 2 RTA may show symptoms and signs of hypokalemia, including muscle weakness, hyporeflexia, and paralysis. Type 4 RTA is usually asymptomatic with only mild acidosis, but cardiac arrhythmias or paralysis may develop if hyperkalemia is severe. Signs of ECF volume depletion may develop from urinary water loss accompanying electrolyte excretion in type 2 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 Cl, HCO 3 , or a loop diuretic)

RTA is suspected in any patient with unexplained metabolic acidosis (low plasma HCO 3 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 K supplements, K-sparing diuretics, or chronic kidney disease. ABG sampling is done to help confirm RTA and to exclude respiratory alkalosis as a cause of compensatory metabolic acidosis. Serum electrolytes, BUN, creatinine, and urine pH are measured in all patients. Further tests and sometimes provocative tests are done, depending on which type of RTA is suspected:

  • 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 Cl, 100 mg/kg po). Normal kidneys reduce urine pH to < 5.2 within 6 h of acidosis.

  • Type 2 RTA is diagnosed by measurement of the urine pH and fractional HCO 3 excretion during an HCO 3 infusion (NaHCO 3 , 0.5 to 1.0 mEq/kg/h IV). In type 2, urine pH rises above 7.5, and the fractional excretion of HCO 3 is > 15%. Because IV HCO 3 can contribute to hypokalemia, K supplements should be given in adequate amounts before infusion.

  • Type 4 RTA is confirmed by a transtubular K concentration gradient of < 5 (normal value > 10 if serum K is high), which indicates inappropriately low urinary K excretion, suggesting hypoaldosteronism or tubular unresponsiveness to aldosterone. Calculation of the gradient assumes that the urine sodium is > 25 mEq/L and urine osmolality is greater than serum. It is calculated by


Definitive diagnosis of hyporeninemic hypoaldosteronism can be obtained by measuring plasma renin and aldosterone levels after provocation (eg, administering a loop diuretic and having the patient remain upright for 3 h) but is usually not necessary.


  • Varies by type

  • Often alkali therapy

  • Treatment of concomitant abnormalities related to K, Ca, and phosphate metabolism

Treatment consists of correction of pH and electrolyte balance with alkali therapy. Failure to treat RTA in children slows growth.

Alkaline agents such as NaHCO 3 , KHCO 3 or Na citrate help achieve a relatively normal plasma HCO 3 concentration (22 to 24 mEq/L). K citrate can be substituted when persistent hypokalemia is present or, because Na increases Ca excretion, when Ca calculi are present. Vitamin D (eg, ergocalciferol 800 IU po once/day) and oral Ca supplements (elemental Ca 500 mg po tid, eg, as Ca carbonate, 1250 mg po tid) may also be needed to help reduce skeletal deformities resulting from osteomalacia or rickets.

Type 1 RTA

Adults are given NaHCO 3 or Na citrate (0.25 to 0.5 mEq/kg po q 6 h). In children, the total daily dose may need to be as much as 2 mEq/kg q 8 h; this dose can be adjusted as the child grows. K supplementation is usually not required when the dehydration and secondary aldosteronism are corrected with HCO 3 therapy.

Type 2 RTA

Plasma HCO 3 cannot be restored to the normal range, but HCO 3 replacement should exceed the acid load of the diet (eg, NaHCO 3 1 mEq/kg po q 6 h in adults or 2 to 4 mEq/kg q 6 h in children) to maintain serum HCO 3 at about 22 to 24 mEq/L because lower levels risk growth disturbance. However, excess HCO 3 replacement increases KHCO 3 losses in the urine. Thus, citrate salts can be substituted for NaHCO 3 and may be better tolerated.

K supplements or K citrate may be required in patients who become hypokalemic when given NaHCO 3 but is not recommended in patients with normal or high serum K levels. In difficult cases, treatment with low-dose hydrochlorothiazide (25 mg po bid) may stimulate proximal tubule transport functions. In cases of generalized proximal tubule disorder, hypophosphatemia and bone disorders are treated with phosphate and vitamin D supplementation to normalize the plasma phosphate concentration.

Type 4 RTA

Hyperkalemia is treated with volume expansion, dietary K restriction, and K-wasting diuretics (eg, furosemide 20 to 40 mg po once/day or bid titrated to effect). Alkalinization is often unnecessary. A few patients need mineralocorticoid replacement therapy (fludrocortisone 0.1 to 0.2 mg po once/day, often higher in hyporeninemic hypoaldosteronism); mineralocorticoid replacement should be used with caution because it may exacerbate underlying hypertension, heart failure, or edema.

Key Points

  • Renal tubular acidosis is a class of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO 3 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 H + excretion (type 1) or impaired HCO 3 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, transtubular K gradient for type 4).

  • Treat using alkali therapy and measures to correct serum K (eg, K restriction or K-wasting diuretics) and other electrolytes.

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