Renal Tubular Defects in Dogs and Cats

Uncommon renal tubular defects in dogs and cats can result in abnormal handling of acid-base processes in the nephron. The result is hyperchloremic metabolic acidosis with a normal anion gap, referred to as renal tubular acidosis (RTA).

Distal (type 1) RTA occurs when there is impaired synthesis of bicarbonate in the distal nephron, resulting in failure of the distal nephron to secrete hydrogen ions and acidify the urine. Distal RTA has been reported in dogs and cats in association with various drugs and underlying disease triggers. 

Animals with distal RTA have hyperchloremic metabolic acidosis (see video) with a normal anion gap and alkaline urine. Often they are hypokalemic, lethargic, and weak from acidosis and hypokalemic myopathy. Distal RTA can result in demineralization of the skeleton and nephrolithiasis.

Overview of Metabolic Acidosis

video

Diagnosis of distal RTA is based on the presence of hyperchloremic metabolic acidosis with a urinary pH that is inappropriately high for the degree of systemic acidosis in the absence of bacterial urease modification of urine. Failure to produce acidic urine in the face of metabolic acidosis or after oral ammonium chloride loading is diagnostic; however, diagnosis is often presumptive.

Proximal (type 2) RTA results from impaired bicarbonate reabsorption in the proximal tubule. As in distal RTA, hyperchloremic metabolic acidosis with a normal anion gap results; however, in proximal RTA the animal retains the ability to acidify urine. 

Proximal RTA most commonly occurs in conjunction with other proximal tubule defects (eg, Fanconi syndrome). Proximal RTA is diagnosed by demonstration of increased urinary fractional excretion of bicarbonate when plasma bicarbonate concentrations are normal or decreased. Because this test is not practical in the clinical setting, diagnosis is presumptive, based on history, signalment, and clinicopathological findings. 

Treatment for both distal and proximal RTA involves addressing the potential underlying cause, supplementing with potassium, and supplementing with an alkali source such as potassium citrate or sodium bicarbonate.

Fanconi syndrome is a generalized proximal tubular reabsorptive defect characterized by glucosuria, aminoaciduria, phosphaturia, renal tubular acidosis, and abnormal reabsorption of other electrolytes, including sodium and potassium.

Fanconi syndrome is a heritable disorder in Basenji dogs and, uncommonly, in dogs of other breeds. 

Acquired Fanconi syndrome has been connected to several factors, including ingestion of chicken jerky treats, copper storage disease in dogs, chlorambucil administration in cats, primary hypoparathyroidism in dogs, leptospirosis in dogs, gentamicin administration, and various other drugs and toxicities that can affect the proximal renal tubule. 

Clinical signs of Fanconi syndrome include polyuria/polydipsia, dehydration, weight loss, weakness, and poor coat. The disease can progress to renal failure with clinical signs associated with uremia. The presence of normoglycemic glucosuria and/or proximal RTA often alerts the clinician to the potential for Fanconi syndrome. Serum electrolyte concentrations are normal early in the disease; however, hypophosphatemia, hypokalemia, and metabolic acidosis occur in the later stages. 

Diagnosis of Fanconi syndrome is based on documentation of increased urinary fractional excretion of glucose, sodium, potassium, phosphorus, and bicarbonate in the presence of normal plasma concentrations. A commercial urine test is available to test for the presence of aminoaciduria, glucosuria, and other components consistent with Fanconi syndrome. 

Management of Fanconi syndrome involves fluid support and electrolyte (usually potassium) supplementation as needed, along with administration of an alkali source (sodium bicarbonate) to manage metabolic acidosis. Sodium bicarbonate can exacerbate hypokalemia, in which case potassium citrate can be used to manage metabolic acidosis. 

An aggressive supplementation protocol known as "Gonto protocol" has been used to manage the heritable form of Fanconi syndrome in Basenji dogs. Although the efficacy and safety of this protocol have not been rigorously studied and compared to alternative management protocols, longterm survival in dogs managed with the Gonto protocol has been reported. 

Several acquired causes of Fanconi syndrome are reversible, and animals can fully recover with appropriate support and attention to the underlying cause. 

Dogs with idiopathic Fanconi syndrome can have a near-normal lifespan and good quality of life with appropriate management; however, the disease can progress to end-stage renal failure.

Renal glucosuria is usually due to a congenital defect in proximal tubular handling of glucose that results in glucosuria despite normal blood glucose concentration. Animals with renal glucosuria can be subclinically affected, have polydipsia/polyuria, or have recurrent or severe urinary tract infections due to bacterial colonization in the presence of glucose.

Renal glucosuria is diagnosed by demonstration of persistent glucosuria despite a normal blood glucose concentration and by lack of identification of other renal reabsorptive abnormalities.

Renal glucosuria is so uncommonly recognized that little is known about its biological behavior. The general consensus is that it is not progressive and does not require treatment, except in some animals with heritable Fanconi syndrome that initially exhibit glucosuria as the only clinically apparent renal reabsorptive defect.

• Riordan L, Schaer M. Renal tubular acidosis. Compend Contin Educ Pract Vet. 2005;27:513-529.

• Yearley JH, Hancock DD, Mealey KL. Survival time, lifespan, and quality of life in dogs with idiopathic Fanconi syndrome. J Am Vet Med Assoc. 2004;225(3):377-383.

• Also see pet owner content regarding noninfectious diseases of the urinary system in dogs and cats.