The form of metabolic acidosis that occurs in acute kidney injury and Stages 2–4 of chronic kidney disease, referred to as uremic acidosis, is due to reduced urine-acidifying ability of diseased kidneys. In uremic acidosis, although the ability of individual tubular cells to reabsorb bicarbonate and/or secrete hydrogen ions may be normal, there is generally far less total cell mass present. Acid accumulates if the animal is under metabolic or dietary acid pressure, which is common in carnivores. This is particularly problematic in cats, which are often fed acidifying maintenance diets.
Rare renal tubular defects in dogs and cats may result in hyperchloremic metabolic acidosis, referred to as renal tubular acidosis. Two types of renal tubular acidosis have been described in dogs and one in cats. In Type I (distal), the ability of the distal tubule to secrete hydrogen ions against a concentration gradient is defective; in Type II (proximal), the ability to reabsorb bicarbonate in the proximal tubule is reduced. Type I has been reported in both species; Type II has also been described in dogs in conjunction with other proximal tubular defects in acquired (gentamicin nephrotoxicosis and an idiopathic form) and heritable (Fanconi syndrome, see Fanconi Syndrome) forms.
Type I renal tubular acidosis has been associated with demineralization of the skeleton (due to buffering of excess hydrogen ions) and nephrolithiasis (due to hypercalciuria from bone resorption) in dogs. Diagnosis 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 acid urine in the face of metabolic acidosis or after oral ammonium chloride loading is diagnostic; however, this challenge test is contraindicated in animals that are already severely acidotic. Type II renal tubular acidosis is diagnosed by demonstrating increased urinary fractional excretion of bicarbonate when plasma bicarbonate levels are normal or decreased; this test is not practicable in the clinical setting and diagnosis is presumptively based on history, signalment, and clinical pathology findings.
Therapy consists of oral administration of an alkalinizing agent sufficient to maintain normal blood pH (1 mEq bicarbonate equivalent/kg/day for Type I and 1–6 mEq bicarbonate equivalent/kg/day for Type II, PO). Therapy is more problematic in dogs with Type II renal tubular acidosis, because supplemental bicarbonate is readily lost in the urine.
Fanconi syndrome is a generalized proximal tubular reabsorptive defect resulting in excessive loss of many solutes in the urine. It has been reported as an acquired condition in dogs (chicken jerky treat ingestion, gentamicin nephrotoxicosis, and an idiopathic form) and in a heritable form in a variety of breeds (most notably Basenjis), in which it develops gradually in adults of both sexes. There is excessive urinary loss of glucose, sodium, potassium, phosphorus, uric acid, bicarbonate, albumin, and amino acids. Blood glucose concentrations are normal. Serum electrolytes are normal early in the disease, but hypophosphatemia, hypokalemia, and metabolic acidosis are seen in the later stages.
Clinical signs include polydipsia, polyuria, and weight loss. Signs of uremia may be present if the animal is in Stage III or IV chronic kidney disease. Diagnosis is based on documentation of increased urinary fractional excretion of glucose, sodium, potassium, phosphorus, and bicarbonate in the presence of normal plasma concentrations. Hypoalbuminuria is likely to be present, as the proximal tubule normally reabsorbs the small amount of albumin that traverses the glomerular filtration barrier. Differential diagnoses include simple renal glucosuria and chronic kidney disease from other causes. The microscopic renal changes in the heritable form are not remarkable in the early stages but progress to nonspecific findings characteristic of chronic kidney disease. A genetic marker has been developed. A treatment regimen to reverse the tubular defect has not been described. The histologic appearance of the acquired forms of Fanconi syndrome vary, depending on the cause.
Oral supplementation of sodium chloride (5–10 mg/kg/day, PO), potassium (potassium citrate 10–30 mg/kg/day, PO), and alkali (potassium citrate 10–30 mg/kg/day, PO) is indicated if the corresponding serum concentration is low. Dogs with acute or chronic kidney disease should be treated symptomatically as appropriate. The heritable disease is slowly progressive despite therapy and usually results in death from uremia.
This is usually a congenital defect in proximal tubular handling of glucose that results in glucosuria despite normal blood glucose concentration. Affected animals may be asymptomatic, have polydipsia and polyuria, or have recurrent or severe urinary tract infections due to bacterial colonization in the presence of glucose. Diagnosis is made by demonstrating persistent glucosuria despite a normal blood glucose concentration and by identifying no other renal reabsorptive abnormalities. This disease is so uncommonly recognized that little is known about its biologic behavior. The general consensus is that it is not progressive and does not require treatment, except that some animals with heritable Fanconi syndrome may initially exhibit glucosuria as the only clinically apparent renal reabsorptive defect.
Last full review/revision October 2013 by Scott A. Brown, VMD, PhD, DACVIM