Pertemuan Kesembilan

Clinical Nutrition untuk

Urolithiasis pada Anjing
KRP 413 Contoh kasus: Canine Clinical Nutrition
 Definition
Urine
1. Urine: a complex aqueous solution of organic
and inorganic solutes
2. More of a given solute can remain in solution in
urine than in water due to the complex
interactions among the various constituents of
urine
3. Urine is commonly supersaturated with
crystalloids
4. Observation of individual crystal types in urine
does not necessarily mean the patient is at risk
for developing urolithiasis
Factors Supersaturation (RSS>>1)
Nucleation will accur:
Spontaneous crystallization
Rapid crystal growth and
aggregation
Dissolution is not possible
Metastable zone (RSS>1)
Possible growth of preformed
crystals
Heterogeneous nucleation may
occur
Dissolution is not possible
Undestasuration
(stable)(RSS<1)
No crystallization
Existing uroliths/crystals may
dissolve
Urolithiasis
• Supersaturation
(solubility product
exceeded) of urine
with a crystalloid
depends on:
1. Amount of solute
ingested and excreted
2. Urine volume
3. Urine pH
4. Promoters
5. Inihibitors
Influence:
Solubility & pH
Influence: Effect of Metabolic Asidosis on
Calcium Oxalate Formation
Diagnosis
 Factors Predicting Urolithiasis Evidences
Radiograph Calcium Oxalate/C Phospate: ++++
Density Struvite, Silica: ++ to ++++
Cystine: + to ++
Amonium Urate: 0 to +
Urine pH Struvite  usually Alkaline
Calcium Oxalate  No Predisposition
Amonium Urate/Silica  Acid to Neutral
Cystine  Acid
Crystalluria Patognomonic for cystine crystal

Present of UTI Urease of bacteria: staphylococci, proteus

Diseases Hypercalcemia  calcium containing urolith

Association Portosystemin shunt  urate urolithiasis
Hyperchloremia, Hypokalemia, acidosis  calcium
phospate, struvite
Urine Chemistry Urine relative supersaturation
Character of Urolithisis
Struvite C. Oxalate Urate Cystine
Calcium Oxalate Makroskopis
Calcium Oxalate Mikroskopis
Calcium Oxalate Makroskopis
Calcium Oxalate Mikroskopis
Statistics
Prevalence of stone types
Stone type Dogs Cats
Number 77,190 20,343
Struvite 50% 43%
Oxalate 31% 46%
Urate 8% 6%
Cystine 1% < 1%
Silicate 1% < 0.1%
Calcium phosphate < 1% < 1%
Data from University of Minnesota Stone Laboratory 2000
 Feline
Urolithiasis
 Risk Factors for Urolith Formation Linked to
Diet Urine Composition & Metablism in Dogs
Uroliths Diet Urine Metabolic/Other
Struvite High Magnesium Alkaline pH
High Phosporus UTI with urease
Low water consumption producing bacteria
Low Urine Volume
Calcium High Calcium Low Urine Volume Hypercalcemia
Oxalate High oxalate (esp. When Hypercalciuria Hyperadrenocorticm
dietary Calcium is low) Hyperoxaluria Chronic metobolic acidosis
Excess Vit C.
Calsium Excess dietary Calcium & Hypercalcemia (primary
Phosphate Phosporus hyperthiroidism
Urate High purine diets (eg: Genetically defect in uric acid
diet rich offal) metabolism
Hepatic dysfunction
Cystine Cysturia Defective proximal tubular
reabsorption of Cystine and
other basic amino acids
Cilica High dietary silica
 Age, Bredd and Sex Predisposition for
Urolithiasis in Dogs
Uroliths Age Breed Sex
Struvite 1-8 years Mean 6 Miniatur schnauzer, Bichon frise, Shih Tzu, Female
years Miniatur Poodle 80%

Calcium 6-12 years Miniatur schnauzer, Laza Apzo, Chairen Terrier, Male
Oxalate Mean 8.5 year Yorkshire Terrier, Cocker Spaniel, Bichon fresi, 70-%
Shi Tzu, Miniatur Poodle
Calsium 5-13 years Yorkshire Terier Male
Phosphate 70%
Urate With PSS: < 1year Dalmatian, Old English Bolldog, Male
Without PSS: 3.5 Schnauzer (PSS) 85%
year Yorkshire Terrier
Cystine 2-7 years English Bulldog, Male
Mean 5 years Daschund 90%
Newfoundland dog
Silica 4-9 years German Sheperd Dog Male
Old Englsih Shepdog 90%
Pathogenesis

General theories of urolithiasis

1. Matrix-nucleation theory
2. Precipitation-crystallization theory
3. Crystallization-inhibition theory
4. Some combination of the above?
 1. Matrix-nucleation theory

matriks urolith
terbentuk dgn
promotor UTI:
mikrobial
urease
UTI & Urolith
2. Precipitation-crystallization theory
Urolithiasis: Crystal growth:
• Homogenous nucleation: crystals
precipitate spontaneously (unlikely in
urine)
• Heterogenous nucleation: another
substance acts as a nidus for crystal
precipitation (likely in urine)
• Epitaxy: Precipitation of one crystal on the
surface of another
3. Crystallization-inhibition theory
Inhibitors of
crystallization & aggregation
1. Pyrophosphates
2. Diphosphonates
3. Citrate
4. Some cations (e.g. Mg+2)
5. Glycosaminoglycans
6. Nephrocalcin
Naming

Urolithiasis: Naming of stones

• When 70% of the urolith is composed of one
type of crystal it is named for the crystal
• Mixed urolith < 70% one crystal; no identifiable
nidus or shell
• Compound urolith Identifiable nidus of one
crystal with surrounding layers of another crystal
• Matrix urolith Matrix without appreciable
crystalloid
 Basic Medical & Diet Management
General
Management

5 4
3

6
Correction of fluid, 2
electrolyte, and acid-
base disturbances
 General Management
Control strategy  calculi position
General Treatment Considerations
 Cystouroliths may be managed by medical dissolution, voiding
urohydropropulsion, or cystotomy
 Ureteral and urethral stones are less amenable to medical dissolution
because they are not consistently in contact with undersaturated
urine. Ureteroliths, when associated with complete ureteral
obstruction and hydronephrosis mandate surgical removal.
Ureteroliths that are associated with partial ureteral obstruction can
be managed conservatively as they may move into the bladder. With
respect to urethroliths it is often possible to flush them retrograde
into the bladder where they can be managed with medical
dissolution.
 Nephroliths maybe treated by surgical removal, although medical
dissolution for struvite uroliths is a consideration. Benign neglect is
possible In uninfected and non-obstructing nephroliths
 Position of
Calculi

Cystolithiasis

Ureterolithiasis

cystolitrhiasis
General Management

Urolithiasis:
General principles of management
1. Relief of urinary tract obstruction
2. Correction of fluid, electrolyte, and acid-
base disturbances
3. Non-surgical retrieval of uroliths
4. Surgical removal of urolithis (if necessary)
5. Medical dissolution of uroliths
6. Preventive therapy
General Management

1. Urolithiasis General Approach to :

Relief of obstruction
• Passage of small
diameter, well-lubricated
catheter beyond urethral
obstruction
• Urohydropropulsion
• Decompression by
cystocentesis
• Emergency urethrotomy
General Management

2. Urolithiasis: General principles of

management Induction of polyuria with NaCl
• Aim to decrease USG to < 1.025 (decreased
concentration of crystalloids)
• Allow animal to vomit frequently
• Only recommended for struvite stones
• 0.5 to 10 grams salt per day (1 tsp NaCl = 6 g
NaCl)
• No controlled studies for this
recommendation
General Management
3a. Urolithiasis: Nonsurgical removal of
urolith Voiding urohydropropulsion
• Stones must be small
– < 7 mm in female dog
– < 5 mm in male dog or
female cat
• General anesthesia
• Distend bladder with
saline via cystoscope
• Radiograph afterward

From Lulich JP et al. JAVMA 203:660, 1993.

General Management
3b. Urolithiasis: Nonsurgical removal of uroliths
Catheter-assisted retrieval of uroliths
Small stones can be
collected from
male dog for
quantitative
analysis

From Lulich JP et al. JAVMA 201:111, 1992.

General Management

3c. Urolithiasis: Nonsurgical

removal of uroliths Lithotripsy
• Electrohydraulic shock wave lithotripsy Shock
wave generated in close proximity to urolith in
bladder under cystoscopic visualization
• Extracorporeal shock wave lithotripsy Shock wave
generated outside of body and transmitted to
patient through water (used for nephroliths and
ureteroliths)

Requires special equipment and expertise

 General Management
4. Medical Dissolution vs. surgical

Calcium phosphate uroliths cannot be

medically dissolved, and surgical removal is
usually necessary. Correction of underlying
metabolic abnormalities may minimize
recurrence. If no underlying cause is found,
management is similar to that of calcium
oxalate urolithiasis.
General Management

Medical Dissolution Strategies

Following removal of compound

(mixed) uroliths, medical dissolution
strategies are usually based on
preventing the reformation of the
mineral that composed the core of
the compound urolith.
General Management

5. Urolithiasis:
Medical dissolution of uroliths

• Protocols devised for struvite, urate, and

cystine
• No effect protocol for oxalate yet
6. Diet for Dessolution & Prevention
Struvite C. Oxalate Urate Cystine
Dietary Management
GENERAL AIM
The general aim of dietary management of
urolithiasis is to reduce supersaturation of urine
with calculogenic substances by:

 Increasing water intake and thus urine volume

to decrease urine crystalloid concentration
 Altering the urine pH to increase the solubility of
crystalloids in the urine
 Changing the diet to decrease the quantity of
crystalloids excreted in the urine
Struvite Management
Struvite urolithiasis
Calculolytic diet (S/d)
• Is it struvite?
– Urease-positive UTI
– Alkalkine urine
– Struvite crystalluria
– Radiodense
calculus

?
Struvite Management

Understanding
the formation
Struvite Management

Struvite urolithiasis
Medical management
• Eliminate UTI
• If urine pH still
alkaline search for
another reason
– Diet
– Metabolic (e.g. distal
RTA)
• Calculolytic diet
Struvite Makroskopis
Struvite Mikroskopis
Makroskopis: Uric Acid
Mikroskopis: Uric Acid
Predisposition Concern

Urolithiasis: General principles of

Management Eradication of UTI
• UTI may predispose to (struvite in dogs) or
complicate (oxalate, urate, cystine)
urolithiasis
• Culture urine to identify UTI
• Treat with appropriate antibiotic therapy
• Follow up diligently to document
eradication of infection
Struvite Management
Struvite urolithiasis
Calculolytic diet (S/d)
Canine
• Low in phosphorus and
magnesium
• High in NaCl
• Canine product low in
protein to reduce urea
availability to urease-
positive bacteria
Struvite Management
Struvite urolithiasis
Calculolytic diet (S/d)
Feline
• Similar to Canine S/d but not
protein-restricted
• Average time for dissolution for
sterile struvite stones: 30 days
• Success rate > 90%
• Don’t add acidifier!
Struvite Management
Struvite urolithiasis
Calculolytic diet (S/d)
• Must eradicate UTI
• Dissolution takes 2 to 3 months; continue for 1
additional month
• Side effects
– PU/PD
– Decreased BUN
– Increased SAP (hepatic isoenzyme)
– Decreased serum phosphorus
– Decreased serum albumin
– Possible passage of nephrolith into ureter
Oxalate Management
Oxalate urolithiasis
Medical management

• Attempts at dissolution have been unsuccessful

• Dietary modifications to prevent recurrence
– Low calcium, low oxalate
– Do not restrict phosphorus (decreased phosphorus may enhance
GI calcium absorption; pyrophosphate is a crystallization inhibitor)
– Do not restrict magnesium (CaOx crystallization inhibitor)
– Do not add NaCl (may increase hypercalciuria)
– Less animal protein (less acidifying)
– Citrate (CaOx crystallization inhibitor)
– Avoid vitamin C
Oxalate Management
Oxalate urolithiasis
Medical management

• Potassium citrate (100-150 mg/kg/day) ?

– CaOx crystallization inhibitor
– Alkalinizing effect may reduce bone release of calcium
• Hydrochlorothiazide 2-4 mg/kg q12h ?
– Reduces urinary calcium excretion in dogs
– Diuretic effect
• Vitamin B6 ? (promotes transamination of oxalate
precursor glyoxylate to glycine
Oxalate Management
Urate Management
Urate urolithiasis
Medical management

Alkalinization
• Uric acid becomes more soluble in acid
urine; urate becomes less soluble*
• Alkalinization decreases urinary NH4+ and
H+ concentrations
• Potassium citrate may be preferable to
NaHCO3 because natriuresis will enhance
calciuresis
* Urate calculi in dogs usually are ammonium acid urate vs uric acid in humans
Urate Management
Urate urolithiasis
Medical management

Allopurinol

• Competitive inhibitor of xanthine oxidase

• Dissolution: 15 mg/kg PO q12h
• Prevention: 5-10 mg/kg PO q12h
• Dogs on allopurinol should be fed low purine
diet to reduce risk of xanthine stone formation
Urate Management
Urate urolithiasis
Diet management
Low Purine Diet
• Diets low in organ-
derived meats may
reduce ingested purine
load
• Low protein, low purine
diet reduces urinary
excretion of urate in
normal dogs
Urate Management
Urate urolithiasis
Diet management
Low Purine Diet
• 10-11% casein-based protein
• Low in purines
• Added potassium citrate
• No supplemental sodium (reduction of USG
probably due to reduced renal medullary
urea content)
Used in both dissolution and prevention protocols
Urate Management
Urate urolithiasis
Diet management
Diet for dissolution & prevention
• Decreases urinary excretion of uric acid,
ammonia, titratable acid
• Increases urinary excretion of bicarbonate
(urine pH 7.0-7.5)
• Avoid in young growing dogs due to low
protein (surgery preferred)
• Avoid in English bulldogs (risk of dilated
cardiomyopathy?)
Urate Management
Urate urolithiasis
Medical management

Dissolution
• Client compliance • Results
indicated by: – Complete dissolution
33%
– Disappearance of
urate crystals from – Partial dissolution 33%
sediment – No dissolution 33%
– BUN < 10 mg/dl • Time to dissolution
– USG < 1.020 – 1 to 10 mos
– Urine pH > 7.0 – Average 3 to 4 mos
 Dissolution of Urate
The medical dissolution of urate calculi
includes a combination of:

• Feeding a low purine diet that has been

designed to dissolve urate calculi
• Alkalinization of the urine
• Increasing urine volume
• Controlling urinary tract infections
• Administering xanthine oxidase inhibitors
(allopurinol)
 Urate Management
Urate urolithiasis
Diet & Medical Management
Prevention
• Feed low protein, low purine diet (e.g. U/d)
• Monitor response (e.g. urate crystals in sediment)
• Add allopurinol 5-10 mg/kg PO q12h if crystalluria
persists
• Continue low protein, low purine diet while using
allopurinol to reduce risk of xanthine stones
Cystine Management

Cystine uroliths can be dissolved

medically, using a combination of:

 Protein-restricted alkalinizing diet

 Increasing urine volume
 Alkalinization of urine (pH around 7.5)
 Administration of thiol-containing
drugs
Cystine Management
Cystine urolithiasis
Medical Management d-penicillamine

• Mixed disulfide 50 X more soluble than cystine in urine

• 30 mg/kg/day divided BID
• Most effective at neutral to alkaline urine pH
• May cause vomiting
Cystine Management
Cystine urolithiasis
Medical Management 2-MPG (tiopronin)
• Dissolution: 20 mg/kg PO q12h
• Prevention: 15 mg/kg PO q12h
• Adverse effects (13% of dogs)
– Aggressiveness
– Myopathy
– Immune-mediated reaction
– Skin lesions
– Abnormal liver function tests
• Signs resolve when drug
discontinued
Cystine Management
Cystine urolithiasis Dissolution
Medical Management Protocol

• 2-MPG (tiopronin) 20 mg/kg PO q12h

• 60% success rate
• Time for dissolution: 1 to 3 mos
• Consider surgery if no dissolution by 3 mos
Cystine Management
Cystine urolithiasis Prevention
Medical Management Protocol
• 2-MPG (tiopronin) 15 mg/kg PO q12h
• Add water (not sodium) to food*
• Alkalinize urine with potassium citrate (100-
150 mg/kg/day)
• Recurrence prevented in 86% of treated
dogs
* Natriuresis may increase urinary excretion of cystine
Cystine Management
Cystine urolithiasis Alkalinization
Medical Management
• Cystine has limited solubility in urine pH range of 5.5-
7.0 (twice as soluble in urine of pH 7.8 as compared
to pH 6.5)
• NaHCO3 can be used at dosage of 1 g per 5 kg but
effectiveness may be limited
• Potassium citrate may be preferable
(natriuresis may increase urinary cystine excretion)
• Potential risk of struvite urolithiasis with urine pH in
alkaline range
Cystine Management
Cystine urolithiasis Dietary
Diet Management modification

• Low protein diet may result in lower USG (less

urea for medullary interstitial hypertonicity)
and increased urine pH
• Prescription Diet U/d has been recommended
Silicate Management

Silicate urolithiasis
Medical Management

• Effect of urine pH on silicate solubility not

established
• Avoid diets high in plant proteins (e.g.
soybean hulls, corn gluten)
• Induction of polyuria ?
• Change water source ?
Carbonate Management

Carbonate urolithiasis
Medical Management

• Specific preventive measures after surgical

removal in horses not reported but recurrence
of solid stones is uncommon
• High grain diet may reduce urine pH and
increase carbonate solubility
 Urolithiasis
Complications
• In dogs, recurrence rate is highest for
metabolic stones (e.g. oxalate, urate,
cystine) and lowest for struvite
• Post-renal azotemia and associated fluid,
electrolyte, acid-base imbalances
• Drug and special diet side effects
• Urinary tract infection
Terimakasih