Nutrition and Urolithiasis
Joe Bartges, DVM, PhD, DACVIM, DACVN
Claudia Kirk, DVM, PhD, DACVIM, DACVN, Knoxville, TN
UROLITH FORMATION
Urolithiasis is a common cause of disease in dogs and cats and affects the upper and lower urinary tracts. Medical dissolution and
preventative protocols are available for urolithiasis and dietary modification is an important part. Urolith formation occurs when
urine is oversatured with the calculogenic minerals. Risk factors include breed, gender, age, diet, metabolic status, and chemical
composition of urine. Although microscopic crystalluria likely precedes uralith formation, not all animals with crystallura form
uroliths and urolths can be present without crystalluria. Once urolith formation has been initiated, the urolith nidus must be
retained within the urinary tract, and the urinary environment must favor continued precipitation of minerals, aggregation of these
‘minerals, and growth of the roth. Alterations in balance between urine concentrations of calculogenic substances and calculogenic
inhibitors result in initiation and growth of urolits.”
STRUVITE
‘Struvite is magnesium ammonium phosphate hexahydrate and can occur as a consequence of a bacterial urinary tract infection
(infection induced struvite) or without a urinary tract infection (sterile struvite. infection-induced struvite occurs commonly in dogs
and occasionally in cats, while sterile struvite occurs commonly in cats and rarely in dogs**
Infection-induced struvite
Infection-induced struvite uroliths form as a consequence of a bacterial urinary tract infection with a microbe that produces urease;
Staphylococcus spp occur most commonly. Microbial urease results in oversatuation of urine with struvite calculogenic substances
by metabolizing urea to ammonia, producing alkali, altering the ionization state of phosphorous, and increasing urinary
inflammatory proteins and cells that are incorporated into the urolith. Infection-induced struvite uroliths can be dissolved by
‘administering an appropriate antimicrobial agent and feeding a diet to decrease urine to an undersaturated state with regards to
struvite, Such a diet is, in comparison with adult maintenance diets, relatively lower in protein resulting in less available urinary urea
for microbial urease metabolism, lower in phosphorous, lower in magnesium, acidifying, and diuresing:” The antimicrobial agent
‘must be administered until dissolution is documented to occur. Average time of dissolution is approximately 2 months. Prevention
of infection induced struvite urolths is accomplished by preventing, controlling and treating bacterial urinary tract infections.
Although diets formulated to decrease urinary saturation with struvite are available, they have limited usefulness and indication
because its the infection with a urease-producing microbe that causes infection-induced struvite urolth formation.
Sterile struvite
Stefile struvite urolths form typically in 1-10 year old cats, although they have been reported to occur rarely in dogs” Sterile struvite
Luroliths form because of dietary influence on urine composition as well as innate risks for urolith formation. Experimentally,
‘magnesium phosphate and struvite uroiths formed in healthy cats consuming calculogenic diets containing 0.15 to 1.0% magne-
sium (dry matter basis)” These data are difficult to interpret, however, because the amount of magnesium consumption by cats in
these studies may be different in than cats that spontaneously form sterile struvite urolths consuming commercial diets due to
differences in caloric density, palatability, and digestibility. The influence of magnesium on struvite formation depends on urine pH*
and influence of ions, minerals, and other components in urine.” Alkalura is associated with increased risk for struvite formation."
Ina clinical study including 20 cats with naturally occuring struvite urocystoliths and no detectable bacterial urinary tract infection,
the mean urinary pH atthe time of diagnosis was 69 + 0.4. An additional factor is water intake and urine volume. Consumption
of increased quantities of water may result in lowering concentrations of clculogenic substances in urine, thus, decreasing risk of
Lrolith formation.’* Consumption of small quantities of food frequently rather than one or two large meals per day is associated
\with production of more acidic urine and 2 lesser degree of struvite cstalluria by cats.” Sterile struvite uroliths can be dissolved
by feeding a diet that is restricted in magnesium, phosphorous, and protein, and that induces aciduria relative to adult maintenance
‘at foods.” In a dinical study including 22 cats with sterile struvite urocystoiths, urocystoliths dissolved in 20 cats in a mean of
36.2 + 266 days (range, 14 to 141 days). The cats were fed a high-moisture (canned), caloricaly dense diet containing 0.058%
‘magnesium (dry matter basis) and increased sodium chloride (0.79% dry matter basis) that induced a urine pH of approximately
6.0. Prevention of stele struvite uroliths involves inducing a urine pH less than approximately 6.5, increasing urine volume, and.
decreasing excretion of magnesium, ammonium, and phosphorous.
CALCIUM OXALATE
Calcium oxalate urolith formation occurs when urine is oversaturated with calcium and oxalate’ In addition to these alterations
in activities of ions, large molecular weight proteins occurring in urine, such as nephrocalcin, uropontin, and Tamm-Horsfal
‘mucoprotein, influence calcium oxalate formation." Hypercalciuria isa significant risk factor, but not necessarily the cause of
calcium oxalate urolth formation in human beings, dogs, and cats.” Hypercalciuria can result from excessive intestinal absorption
‘of calcium (Gi hyperabsorption), impaired renal reabsorption of calcium (renal leak), and/or excessive skeletal mobilization of
calcium (tesorptive). Hypercalciuria has not been well defined in normocalcemic cats with calcium oxalate urolths but is thought
to occur, Hypercalcemia results in hypercaliuria, which may promote calcium oxalate formation. Approximately 5% of dogs and
3546 of cats with calcium oxalate uroliths are hypercalcemic; primary hyperparathyroidism is the most common cause in dogs and
idiopathic hypercalcemia is the most common cause in cats.
continued on ret pogeyee
Nutrition and Urolithia:
Joe Bartges, DVM, PhD, DACVIM, DACVN
Claudia Kirk, DVM, PhD, DACVIM, DACVN, Knoxville, TN
‘line Prctior™
contd fom prvi pe
‘Metabolic acidosis promotes hypercalciuria by promoting bone tumover (release of calcium with buffers from bone), increasing
serum ionized calcium concentration resulting in increased urinary calcium excretion, and decreased renal tubular reabsorpt
‘calcium. Consumption of diets supplemented with the urinary acidifier ammonium chloride by cats has been associated with
increased urinary calcium excretion.” Significant aciduria (urine pH < 6.2) may represent a isk factor for calcium oxalate formation
because of acidemia and hypercalciuria In addition, acidic urine alters function and concentration of cystal inhibitors. Low urine pH
decreases urinary citrate concentration by increasing renal proximal tubular citrate reabsorption. Acidic urine is known to impair
function of macromolecular protein inhibitors. inhibitors, such as citrate, magnesium, and pyrophosphate, form soluble salts with
calcium or oxalic acid and reduce availabilty of calcium or oxalic acid for precipitation. Other inhibitors, such as Tamm-Horsfall
lycoprotein and nephrocalcn, interfere with the ability of calcium and oxalic acid to combine minimizing crystal formation,
‘aggregation, and growth. Oxalic acid is a metabolic end product of ascorbic acid (vitamin C) and several amino acids, such as
alycine and serine, derived from dietary sources. Oxalic acid forms soluble salts with sodium and potassium ions, but a relatively
insoluble salt with calcium ions. Therefore, any increased urinary concentration of oxalic acid may promote calcium oxalate formation.
Decreased urine volume result in increased calcium and oxalic acid saturation and an increased risk for uroth formation,
‘Medical protocols that will promote dissolution of calcium oxalate uroliths are not curently available; therefore, uroliths must be
removed physically, either surgically or by voiding urohydropropulsion.” Nutritional and/or medical protocols should be considered
to minimize urolth recurrence or prevent further growth of urolths remaining in the urinary tract. Goals of dietary prevention
include: 1) reducing urine calcium and oxalate concentration, 2) promoting high concentrations and activity of urolth inhibitors,
3) reduce urine acidity, and 4) promote dilute urine.
Dietary modification for prevention of calcium oxalate uroliths in dogs and cats includes inducing diuresis, restricting protein,
promoting alkaluria, and restricting calcium. Fr cats with idiopathic hypercalcemia, feeding a higher fiber diet with supplemental
potassium citrate may be effective” Increasing urine volume is a mainstay of preventative therapy for calcium oxalate urolithiasis
in human beings. By increasing water intake, urinary concentrations of calculogenic minerals are reduced. In addition, larger urine
volumes typically increase urine transit time and voiding frequency, thereby reducing retention time for crystal formation and
growth. Feeding cats a canned food is the most practical means of increasing water intake and lowering calcium oxalate urine
saturation. Solubilty of calcium oxalate in urine is minimally influenced by pH; however, epidemiologic studies consistently identity
‘acidifying diets among the most prominent risk factors for calcium oxalate urolithiasis*~* Furthermore, aciduria promotes
hhypocitratura, and functional impairment of endogenous urolith inhibitors Potassium citrate is often included in diets designed
{or calcium oxalate prevention. In urine, citric acid combines with calcium to form soluble complexes, thereby reducing ionic calcium
concentration. Citric acid also directly inhibits nucleation of calcium and oxalate crystals. Consumption of high levels of sodium may
‘augment renal calcium excretion in human beings. Recent studies in healthy cats and dogs did not find increased urine calcium
excretion in response high dietary salt intake" Urinary magnesium forms complexes with oxalic acid, reducing the amount
of oxalic acid available to form calcium oxalate. Studies in cats associate low dietary magnesium with calcium oxalate risk.
There are currently, several commercial diets available for dogs and cats that meet these nutritional recommendations.
URATE
Uric acd is one of several biodegradation products of purine nucleotide metabolism.” In most dogs and cats, allantoin is the major
‘metabolic end product: its the most soluble of the purine metabolic products excreted in urine. Ammonium urate is the monobasic
ammonium salt of uric acid, and it is the most common form of naturally occurring purine uroliths observed to occur in dogs and
‘as Urate urliths may occur as a consequence of liver disease, specially @ portal vascular anomaly, or without the presence
of liver disease, termed idiopathic urate urolithiasis. Uae uroliths occurring in association with portovascular anomalies are most
‘commonly composed of ammonium urate, and often diagnosed before 1 year of age
‘There apparently have been few studies ofthe biological behavior of ammonium urate uroliths in dogs with portal vascular
anomalies” and none in cats. iis logical to hypothesize that elimination of hyperuricuia and reduction of urine ammonium
concentration following surgical correction of anomalous shunts would result in spontaneous dissolution of uroliths composed
primarily of ammonium urate. Appropriate dlinical studies are needed to prove or disprove this hypothesis. Dissolution of urate
Luroliths in dogs without iver disease is possible using a protein-resticted, alkalinizing diet and allopurinol, although the success
rate is approximately 40%.” Restricting dietary protein results in lower concentrations of purine precursors that are converted to uric
‘acid. inducing alkaluria increases solubility of ammonium urate. A similar strategy is used for prevention. Although no studies have
been performed evaluating the efficacy or safety of medical dissolution of urate uroliths in cats with idiopathic urate urolithasis, we
have successfully dissolved urate uroliths in cats using a low protein diet and allopurinol. Until further studies are performed to
confirm the safety and efficacy of medical dissolution, surgical removal remains the treatment of choice for urate urolths in cats.
Prevention of urate urolith recurrence in cats has been > 90% when using a protein restricted, alkalinizing det.
continued on ne poseSW,
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: . Nutrition and Urolithiasi
= 2 Joe Bartges, DVM, PhD, DACVIM, DACN
& (Claudia Kirk, DVM, PhD, DACVIM, DACUN, Knowvll, TN
eS Pelce Precio ™
“eres contiaved tam previous page
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ovee
BBE
Special thanks 19 Dr: Bartges for sharing this information with us!
He is a wonderful speaker and generous educator.IEA CoM CN Lol USMC TANG 2 ORME STOTT
Feline Pract
2008 Research Grant
The American Association of Feline Practitioners (AAFP) will present a research award in 2008 for meaningful research
in feline medicine andor surgery. The $20,000 award will be given to the researcher whose application shows the most
clinical merit
Past research projects and recipients of the award have been:
2007: Evidence of Effective Drug Delivery Using Transdermal
Dr. Dawn M. Boothe, DVM, PhD, DACVIM, DAC
1 Delivery Ssiems in Cats
P, Auburn University, AL
2006:
Prostaglandin E2 Signaling in the Feline Mammary Cancer: A Potential Target for Chemotherapy
Dr Sakhila Banu, Texas A&M University, College Station, TX
2005: Gene Expresion Profiling of Feline Alimentary Lymphoma
Mary Lynn Higginbotham, DVM, MS, DACVIM-Oncology, Auburn University, AL
Enaluation of Gstatin C as an Endogenous Marker of Glomerular Filtration Rate in Cats
‘Thomas Graves, DVM, PhD, DACVIM, University of Illinois, Urbana, IL
2003: The Awociaton of Bartonella sp. Infection with Chronic Stomatitis in Cats
Kristy L. Dowers, DVM, DACVIM-Clinical Sciences, Colorado State University, Ft. Collins, CO
2002: Mitacantrone and Piroxicam Versus Piraxicam Therapy Alone for the Treatment of Feline Oral
Squarmous Cell Carcinoma
Carolyn Henry, DVM, University of Missouri-Columbia, Columbia, MO
For more information go to wwve.aafponline.org for grant application and instructions, including the criteria for grant
selection, and a time line for the grant and reporting process
All appl
ions and 10 copies of the proposal must be received in the AAFP office by December 15, 2007.
AAFP, 203 Towne Centre Drive, Hillsborough, NJ 08844
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