Page 267 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

258 ACID-BASE DISORDERS

presence of the proximal tubular defect. Thus, proximal normal initially but decreased later in the course of the
RTA can be viewed as a “self-limited” disorder in which disease. Hypokalemia has also been observed late in the

plasma HCO 3 stabilizes at a lower than normal concen- course of the disease. 80 Death usually results from acute
tration after the filtered load falls sufficiently enough that renal failure and papillary necrosis or acute pyelonephri-

distal HCO 3 reabsorption can maintain plasma HCO 3 tis. A distinctive renal lesion is hyperchromatic
at a new but lower steady-state concentration. Mutations karyomegaly of renal tubular cells.
in renal tubular transport proteins, such as the electro- Fanconi syndrome has been observed sporadically in
þ 73 81,143,156,182,213
genic basolateral Na / 3HCO 3 cotransporter and other breeds and has been reported in
þ
þ
one of the five forms of the luminal Na /H antiporter, association with administration of some drugs. 16,28,160
have been implicated in the pathogenesis of inherited In one case, Fanconi syndrome developed in association
forms of proximal renal tubular acidosis in humans. 118 with primary hypoparathyroidism and resolved after treat-
Other abnormalities of proximal tubular function typ- ment with calcium and calcitriol. 88 Rickets in growing
ically accompany impaired HCO 3 reabsorption in prox- children and osteomalacia in adults are features of Fanconi

imal RTA, and these include defects in glucose, syndrome in human patients that usually are not observed
phosphate, sodium, potassium, uric acid, and amino acid in affected dogs. However, congenital Fanconi syndrome
reabsorption. This combination of proximal tubular and renal dysplasia were associated with histologic features
defects is known as Fanconi syndrome. Serum potassium of rickets in two Border terriers. 64 The skeletal
concentration usually is normal in affected human abnormalities in one of the affected dogs resolved after
patients at the time of diagnosis, but alkali therapy may treatment with calcitriol and potassium phosphate. Tran-
precipitate hypokalemia and aggravate urinary potassium sient Fanconi syndrome and proximal renal tubular acido-
wasting, presumably by increasing distal delivery of sis also have been reported in a dog with high liver enzyme
sodium and HCO 3 . activities, and toxin exposure was considered as a possible

The diagnosis of proximal RTA is made by finding an explanation. 115 Idiopathic transient renal tubular dys-
acid urine pH (<5.5 to 6.0) in the presence of function also has been reported in a Labrador retriever 126
1
hyperchloremic metabolic acidosis and a normal GFR and greyhound. Fanconi-like syndrome occurred in Aus-
but an increased urine pH (>6.0) and increased urinary tralian dogs that had been fed dried chicken treats from

fractional excretion of HCO 3 (>15%) after plasma China in 2007 and another product (not containing

HCO 3 concentration has been increased to normal by chicken and not from China) in 2009. 87 Affected dogs
alkali administration. If present, the detection of other had polyuria, polydipsia, glucosuria, acidosis, hypokale-
defects in proximal tubular function (e.g., glucosuria with mia, hypophosphatemia, and azotemia. Most of them sur-
normal blood glucose concentration) establishes the vived with conservative medical management. Finally,
diagnosis. Correction of metabolic acidosis by alkali ther- Fanconi syndrome has been reported in several dogs with
apy is more difficult in proximal RTA than in distal RTA copper storage hepatopathy, and tubular dysfunction
because of the marked bicarbonaturia that occurs when resolved after copper chelation therapy. 10,111

plasma HCO 3 concentration is increased to normal. In one report, an 8-year-old female German shepherd
Alkali dosages in excess of 10 mEq/kg/day may be had hyperchloremic metabolic acidosis, polyuria, poly-

required to correct the plasma HCO 3 concentration, dipsia, isosthenuria, glucosuria with normal blood glu-
and such therapy may result in frank hypokalemia. Thus, cose concentration, and alkaline urine pH (7.46) after
potassium citrate may be the preferred source of alkali. oral administration of NH 4 Cl. 70 The metabolic acidosis
Multiple renal tubular reabsorptive defects resembling was unresponsive to NaHCO 3 administration at dosages
Fanconi syndrome have been reported in young basenji up to 4 mEq/kg/day. This dog appeared to have distal
dogs. 26–28,80 Clinical findings included polyuria, polydip- (type 1) RTA and renal glucosuria. In another case of
sia, weight loss, dehydration, and weakness. Affected apparent distal RTA, a 5-year-old mixed breed dog was
dogs had abnormal fractional reabsorption of glucose, presented for evaluation of anorexia and was determined
bicarbonate, phosphate, sodium, potassium, and urate, to have alkaline urine pH with hyperchloremic metabolic
and they had isolated cystinuria or generalized aminoac- acidosis. 191 In another report, an 8-year-old female Ger-
iduria. The renal tubular disorder in affected basenji dogs man shepherd was presented for polyuria, polydipsia,
is thought to be the result of a metabolic or membrane weight loss, and lethargy. 24 It had a normal GFR, meta-
defect affecting sodium movement or increased back leak bolic acidosis, hyposthenuria, and intermittent
or cell-to-lumen flux of amino acids. In one study, brush glucosuria. Fractional reabsorption of sodium, glucose,
border membranes isolated from basenji dogs with and HCO 3 was decreased, but reabsorption of chloride,

Fanconi syndrome had decreased sodium-dependent glu- phosphate, potassium, urate, and amino acids was nor-
cose transport but no abnormality of cystine uptake mal. The dog gained weight, and its clinical signs were
despite the observed reabsorptive defect for cystine. 157 reversed after treatment with NaHCO 3 at approximately
Defective urinary concentrating ability leads to 10 mEq/kg/ day. This dog appeared to have proximal
isosthenuria or hyposthenuria, and the GFR may be (type 2) RTA.