Overview

• A syndrome characterized by hyperchloremic metabolic acidosis due either to decreased bicarbonate reabsorption from the proximal renal tubule (proximal or type 2 RTA) or decreased hydrogen ion secretion in the distal tubule (distal, classic or type 1 RTA) in patients with normal or near normal glomerular filtration rate and absence of diarrhea.
• Aldosterone deficiency or resistance can cause type 4 distal RTA leading to hyperkalemia. Proximal RTA has not been documented as an isolated entity in dogs but has been observed as part of Fanconi syndrome.
• The following discussion is limited to classic distal RTA. In distal RTA, the urine cannot be maximally acidified despite moderately to markedly decreased plasma bicarbonate concentration as a consequence of impaired hydrogen secretion in the collecting ducts. Urine pH typically is above 6.0 (normally urine pH should be 4.5–5.0 in the presence of systemic acidosis).

Signalment

• Reported in 8 dogs and 4 cats
• No apparent breed or sex predilection
• Age range at time of diagnosis, 1–12 years

Signs

• Associated with acidemia and may include lethargy, muscle weakness (may be related to hypokalemia), inappetence, nausea, weight loss, stunted growth, and neurologic signs.
• Other signs depend on the associated diseases (e.g., pyelonephritis).
• Panting.
• Polyuria and polydipsia (usually associated with hypokalemia or calciuresis).
• Vomiting.
• Hematuria and dysuria (secondary to urolithiasis).
• Osteomalacia associated with chronic metabolic acidosis (not yet reported in dogs and cats).

Causes & Risk Factors

• May be primary (i.e., inherited), or secondary to hypercalciuria, toxins, drugs (e.g., amphotericin B), altered calcium metabolism causing nephrocalcinosis (e.g., hypervitaminosis D, primary hyperparathyroidism), autoimmune (e.g., immune-mediated hemolytic anemia, systemic lupus erythematosus, renal transplant rejection), hypergammaglobulinemic disorders (e.g., multiple myeloma, systemic lupus erythematosus), and tubulointerstitial nephropathies.
• In cats, distal RTA has been associated with pyelonephritis (2 cases), hepatic lipidosis (1 case), and idiopathic with secondary hyperaldosteronism (1 case).
• In dogs, clinical cases were idiopathic or associated with immune-mediated hemolytic anemia (3 cases), leptospirosis (1 case), or experimentally-induced renal ischemia.

Differential Diagnosis

Consider other causes of hyperchloremic (normal anion gap) metabolic acidosis (e.g., diarrhea, carbonic anhydrase inhibitors, ammonium chloride, cationic amino acids, post-hypocapnic metabolic acidosis, dilutional acidosis, hypoadrenocorticism). Small bowel diarrhea is the most important differential diagnosis.

CBC/Biochemistry/Urinalysis

• Results vary depending on associated diseases.
• Hypokalemia (due to increased renal excretion) in some animals; may be severe enough to cause muscle weakness.
• Alkaline urine (pH >6.0); rule out urease-positive urinary tract infection (e.g. Staphylococcus aureus, Proteus spp.) as a cause of alkaline urine.

Other Laboratory Tests

Evaluation of blood gases and serum electrolytes indicates hyperchloremic (normal anion gap) metabolic acidosis. Urine pH is >6.0 in distal RTA versus <5.5 in proximal RTA.

Imaging

Radiography-may detect uroliths or osteomalacia (uncommon).

Diagnostic Procedures

• The key diagnostic feature is normal anion gap metabolic acidosis accompanied by an inappropriately alkaline urine pH (>6.0).
• Ammonium chloride tolerance test-administer 200 mg/kg PO in dogs; measure urine pH before and at hourly intervals for 5 hours; empty the bladder hourly. Urine pH in normal dogs decreases to <5.5 within 4 hours. Avoid this test if severe acidosis is present.
• Type 1 and 2 RTA can be differentiated based on response to NaHCO₃ infused at 0.5–1.0 mEq/kg/h. Fractional excretion of bicarbonate will increase markedly in type 2 RTA.

Drug(s)

• Potassium citrate alone or in combination with sodium citrate (depending on the serum potassium concentration) at a total dosage of 1–5 mEq/kg/day PO, divided into two doses, or sodium bicarbonate at 10–50 mg/kg q8–12h PO (1–3 mEq/kg/day).
• Potassium supplementation-potassium gluconate; cats, 2–8 mEq/day divided q12h PO; dogs (depending on body size), 2–44 mEq/day divided q12h PO, if required.

Contraindications/Possible Interactions

Citrate should be avoided in patients with renal failure receiving aluminum hydroxide because citrate increases intestinal permeability and can lead to excessive aluminum absorption.

See Also

• Acidosis, Metabolic
• Fanconi Syndrome
• Hypokalemia

Abbreviations

• NaHCO₃ = sodium bicarbonate
• RTA = renal tubular acidosis

Authors Joao Felipe de Brito Galvao and Stephen P. DiBartola

Consulting Editor Carl A. Osborne