Page 829 - Small Animal Clinical Nutrition 5th Edition

860 Small Animal Clinical Nutrition

absorbed from dietary ingredients. Urine oxalic acid excretion is formigenes to people with Type 1 hyperoxaluria reduced the
VetBooks.ir inversely related to dietary intake of calcium. In the intestinal oxalate concentration in plasma and urine (Hoppe et al,
2006). 3) In rats, O. formigenes colonization induced colonic
tract,oxalic acid complexes with calcium and is excreted in feces
as an insoluble salt. A decrease in the combination of oxalic acid
secretion/excretion of endogenous oxalate and was associated
with calcium to form calcium oxalate results in an increased with reduced oxalate levels in plasma (Hatch et al, 2006).
quantity of soluble oxalic acid available for intestinal absorp- These studies indicate that colonization of ODB in the gas-
tion. Therefore, it is logical to assume that urolith-forming trointestinal (GI) tract can prevent enteric absorption of oxal-
patients with intestinal hyperabsorption of calcium, or those ic acid and increase fecal excretion of endogenously produced
consuming foods with inappropriately low calcium compared oxalate. ODB possess two enzymes, formyl CoA transferase
with oxalic acid, would be at risk for increased intestinal and oxalate CoA decarboxylase, that metabolize oxalic acid to
absorption of dietary oxalic acid, hyperoxaluria and subsequent formate and CO (Lung et al, 1994; Sidhu et al, 1997). In
2
calcium oxalate urolith formation. addition, O. formigenes carries a specialized membrane trans-
porter, oxalate/formate antiporter, to transport the substrate
Hypocitraturia and product across the membrane (Ruan et al, 1992). O.
Hypocitraturia is a common physiologic disturbance in people formigenes, Lactobacillus spp., Bifidobacterium lactis, Entero-
with calcium oxalate urolithiasis. It has been reported to affect coccus faecalis and Eubacterium lentum are major ODB found
20 to 60% of calcium stone formers (Hamm and Hering- in mammalian GI tracts (Allison et al, 1986; Federici et al,
Smith, 2002). Urine citric acid is a negative anion that com- 2004; Hokama et al, 2000; Ito et al, 1996; Weese et al, 2004).
bines with cationic calcium, thus reducing the quantity of cal- O. formigenes, an anaerobe, is solely dependent on oxalate as
cium available to complex with oxalic acid. Calcium citrate is an energy source. It is considered to efficiently degrade
more soluble than calcium oxalate. Citrate is also a buffer, and oxalate in the GI tract of rats, sheep, pigs and people (Allison
as such, minimizes the formation of calcium phosphate. Citrate et al, 1985, 1986; Daniel et al, 1987).
also directly inhibits crystallization and aggregation of calcium There have been few studies reported in which ODB have
oxalate and calcium phosphate (Park and Pearle, 2007). been evaluated in dogs in context of calcium oxalate uroliths.
The role of low urine citric acid concentration in the etiolo- Oxalate-degrading Lactobacillus spp. are present in healthy
gy of canine calcium oxalate urolithiasis is not completely re- dogs and cats (Weese et al, 2004). However, the effect of
solved. Hypocitraturia has been observed in dogs with calcium intestinal colonization with ODB on urine oxalate excretion
oxalate uroliths; however, mechanisms responsible for de- has apparently not been investigated. Oxalate-degrading bac-
creased urine citric acid excretion in dogs are as yet unknown. terial activity in canine feces has been demonstrated (Daniel
It is known that acid-base homeostasis influences the quantity et al, 1987). However, the role of ODB in the pathogenesis of
of citric acid excreted in urine (Simpson, 1983). In normal canine and feline calcium oxalate urolithiasis apparently has
dogs, acidosis is associated with decreased urine citric acid for- not been reported.
mation and excretion, whereas alkalosis promotes urine citric Considering the current evidence derived from human and
acid formation and excretion. rodent models,we hypothesize that decreased concentrations of
Several abnormalities associated with acidosis may lead to intestinal ODB are a likely risk factor for calcium oxalate
hypocitraturia. Examples include distal renal tubular acidosis, urolith formation in dogs and cats (Lulich et al, 2008). We also
chronic diarrhea associated with systemic acidosis and exces- hypothesize that the prevalence of ODB in the intestine of
sive consumption of animal protein, which produces excess dogs with calcium oxalate uroliths is lower than in clinically
acid and promotes bone demineralization. A recent study of a healthy dogs without uroliths. If our hypothesis is correct,
high-protein, low-carbohydrate diet typified by the so-called administration of novel probiotics that deliver viable ODB to
Atkins diet revealed a significant reduction in urinary pH and the intestine and subsequent colonization of the intestinal
citrate during the induction and maintenance phases of the mucosa with O. formigenes should minimize calcium oxalate
diet (Reddy et al, 2002). Hypocitraturia may also occur in urolith recurrence.
association with thiazide-induced hypokalemia, which pro-
duces intracellular acidosis. Idiopathic hypocitraturia may also Macromolecular Crystal Growth Inhibitors
occur independent of acidosis. In addition to urine concentration of lithogenic minerals and
other ions, large molecular weight glycoproteins in urine pro-
The Role of Oxalate-Degrading Bacteria foundly enhance solubility of calcium oxalate. One such protein
Recent studies have revealed a correlation between enteric col- called nephrocalcin minimizes calcium oxalate crystal growth
onization of oxalate-degrading bacteria (ODB), mainly in human urine (Nakagawa et al, 1983). In studies of nephro-
Oxalobacter formigenes, and the absence of hyperoxaluria and/or calcin obtained from urolith-forming patients, this crystalliza-
calcium oxalate formation in rats and people (Sidhu et al, 1999; tion inhibitor lacked appropriate quantities of carboxyglutamic
Troxel et al, 2003). Consider the following evidence: 1) Using acid residues and was unable to prevent crystal growth.
a rat model, one group of investigators demonstrated a rapid Preliminary studies of urine obtained from dogs with calcium
reversal of hyperoxaluria after probiotic administration of O. oxalate uroliths have revealed that nephrocalcin also lacks
formigenes (Sidhu et al, 2001). 2) Oral administration of O. appropriate numbers of carboxyglutamic acid residues com-