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Renal
tubular acidosis is acidosis and electrolyte disturbances due to
impaired renal hydrogen ion excretion (type 1), impaired HCO3 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 renal failure. Diagnosis is based on characteristic
changes in urine pH and electrolytes in response to acid or base
loading. Treatment corrects pH and electrolyte imbalance using alkaline
agents, electrolytes, and, rarely, drugs.
Renal tubular acidosis (RTA) defines a class of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO3 is impaired, leading to a chronic metabolic acidosis (see Acid-Base Regulation and Disorders: Metabolic Acidosis) with a normal anion gap. Hyperchloremia is usually present, and secondary derangements in other electrolytes, such as K and Ca, frequently occur.
Chronic RTA is often associated with structural damage to renal tubules and may progress to chronic renal failure (see Renal Failure: Chronic Kidney Disease (Chronic Renal Failure)).
Type
1 (distal) RTA is an impairment in hydrogen ion secretion in the distal tubule, resulting in a persistently high urine pH (> 5.5) and systemic acidosis. Plasma HCO3 is usually < 15 mEq/L, and hypokalemia, hypercalciuria, and decreased citrate excretion are often present. This syndrome is rare. Sporadic cases occur most often in adults and may be primary (nearly always in women) or secondary to various diseases (eg, autoimmune disease with hypergammaglobulinemia, particularly Sjögren's syndrome or RA; kidney transplantation; nephrocalcinosis; renal medullary sponge kidney; or chronic renal obstruction) or drugs ( amphotericin B , ifosfamide , lithium ). Familial cases usually present in childhood and are most often autosomal dominant; they typically are associated with hypercalciuria and nephrocalcinosis.
Type
2 (proximal) RTA is an impairment in HCO3 resorption in the proximal tubules, producing a urine pH > 7 if plasma HCO3 concentration is normal, and a urine pH < 5.5 if plasma HCO3 concentration is already depleted from ongoing losses. This syndrome may occur as part of a generalized dysfunction of proximal tubules and can be associated with increased urinary excretion of glucose, uric acid, phosphate, amino acids, and protein. The disorder is rare and most often occurs in the context of Fanconi syndrome, light chain nephropathy, multiple myeloma, or various drug exposures ( acetazolamide , sulfonamides, ifosfamide , outdated tetracycline , streptozocin ). Other etiologies include vitamin D deficiency, chronic hypocalcemia with secondary hyperparathyroidism, kidney transplantation, heavy metal exposure, and other inherited diseases (eg, fructose intolerance, Wilson's disease, oculocerebrorenal syndrome [Lowe syndrome], cystinosis).
Type
4 (generalized) RTA results from aldosterone deficiency or unresponsiveness of the distal tubule to aldosterone. Because aldosterone triggers Na resorption in exchange for K and H, there is reduced K excretion, causing hyperkalemia, reduced ammonia production, and reduced acid excretion. However, urine pH is usually normal. Plasma HCO3 is usually in the lower range of normal. This disorder is the most common form of RTA. It typically occurs sporadically secondary to an impairment in the renin-aldosterone-renal tubule axis (hyporeninemic hypoaldosteronism). It may also occur in the context of diabetes mellitus, HIV nephropathy, or interstitial renal damage (SLE, obstructive uropathy, sickle cell disease), infection (cytomegalovirus, Mycobacterium avium complex), and various drugs (eg, NSAIDs, ACE inhibitors, angiotensin II receptor blockers, K-sparing diuretics, trimethoprim , pentamidine , heparin ). Other causes include adrenal insufficiency, congenital adrenal hyperplasia, and genetic disorders (eg, aldosterone synthase type I or II deficiency, pseudohypoaldosteronism type I or II).
Symptoms and Signs
RTA is usually asymptomatic. However, signs of chronic electrolyte abnormalities may become apparent. Ca derangements in type 1 RTA may result in bony involvement (eg, bone pain, osteomalacia, rickets) or calculus formation (eg, nephrolithiasis, nephrocalcinosis).
Severe electrolyte disturbances are rare but can be life threatening. People with type 1 or 2 RTA may show signs and symptoms 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.
Diagnosis
RTA is suspected in any patient with unexplained metabolic acidosis (low plasma HCO3 and low blood pH) with normal anion gap.
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 HCO3 excretion during an HCO3 infusion (NaHCO3, 0.5 to 1.0 mEq/kg/h IV). In type 2, urine pH rises above 7.5, and the fractional excretion of HCO3 is > 15%.
Type 4 RTA is considered in any patient with metabolic acidosis and persistent hyperkalemia without an obvious cause, such as severe renal failure, excessive intake of K supplements, or use of a K-sparing diuretic. A low transtubular K concentration gradient (< 5) indicates inappropriately low urinary K excretion and suggests hypoaldosteronism or tubular unresponsiveness to aldosterone. The gradient is calculated by
Definitive diagnosis can be obtained by measuring plasma renin and aldosterone levels after a stimulus has been applied (eg, administration of a loop diuretic, having the patient remain in the upright position for 3 h) but is usually not necessary.
Treatment
Treatment consists of correction of pH and electrolyte balance with alkali therapy. Failure to treat RTA in children slows growth.
Alkaline agents such as NaHCO3 or Na citrate help achieve a relatively normal plasma HCO3 concentration (22 to 24 mEq/L). K citrate can be substituted when persistent hypokalemia or Ca stone disease is present. Vitamin D ( ergocalciferol , 400 IU po once/day) and Ca supplements (Ca carbonate, 1250 mg po tid or 500 mg elemental Ca2
+) may also be needed to help reduce skeletal deformities resulting from osteomalacia or rickets.
Type
1 RTA:
Adults are given NaHCO3 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.
Type
2 RTA:
Plasma HCO3 cannot be restored to the normal range, but HCO3 replacement should exceed the acid load of the diet (NaHCO3, 1 mEq/kg q 6 h in adults or 2 to 4 mEq/kg q 6 h in children). However, excess HCO3 replacement increases KHCO3 losses in the urine. Thus, citrate salts can be substituted for NaHCO3 and may be better tolerated. K supplements or K citrate may be required in patients who become hypokalemic when given NaHCO3 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). A few patients need mineralocorticoid replacement therapy ( fludrocortisone , 0.1 to 0.2 mg po once/day); this should be used with caution, because it may exacerbate underlying hypertension, heart failure, or edema.
Last full review/revision November 2005
Content last modified November 2005
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