V. Biourge, DVM PhD Dip ACVN&ECVCNRoyal Canin, Centre de Recherche, Aimargues (France)

Dietary management of (reccurent) urolithiasis.

Plan• Lower urinary tract diseases

(LUTD)• Work-up of reccurent

urolithiasis• Urinary stones

• How to determine their composition ?

• Urinary Supersaturation• Dietary management of

stone reccurence.

LUTD: definition

Buffington

Dr. Rosama Pusoonthornthum

LUTD

SyndromeFrequent urination: pollakiuriaPainful urination: dysuriaBlood in urine: hematuriaUrination outside litter box:

periuriaUrethral blockade

LUTD

LUTD: older cats

Most frequent causes81 cats > 10 yr with hematuria and

dysuria• UTI ................................... 46 %• Urolith + UTI ................... 17 %• Uroliths ............................. 10 %• Urethral plugs ................... 7 %• Trauma ............................. 5 %• Idiopathic........................... 5 %

Bartges, 1997

Reccurence of LUTDs

Diagnostic work-up• Clinical and dietary History• Clinical exam

– Palpation– Other clinical signs

• Urine analysis– pH (at home, pH meter)– Specific gravity, Glucose– Hematuria– Bacteria/leucocytes– Crystals (agregates, cystine, urate)

• Urine culture– If risk factors

• Radiology ou echography• Blood biochemistry

– Diabetes, hyperthyroïdism, cushing, renal disease, hypercalcemia, …

Cystine

CVUC

Reccurence of stones

To have in mind• Stone composition might differ

between episodes. • Easy to miss a stone during

surgery (CaOx, urate)• Foreign bodies (suture

material in 9.4% of reccurent stones)

• Urinary crystals do not allow to predict stone composition (except cystine, xanthine and urate in Dalmatian)

CVUC

Urinary stones

Struvite Calcium oxalate

Courtesy of Dr Buffington

Urate

Courtesy of Dr Deschamps

Xanthine Silica Phosphate de CaCystineCVUC WCPN

40-45% 40-45% 6-15%

0.6 Ct-5Cn %< 0.01 %Cn 0.01-2 %Cn <0.01 %Cn-Ct

Simple Vs mixed stones

• Simple– One major mineral

(>70%)– Mineral = 100%

• 61-87 % of stones

• Mixed stones– < 70 %– Nidus

CVUC

CaOx

Struvite

Urinary stone composition

CVUC

Urinary stone composition

CVUC

Urinary stone composition

Optical crystallography X-ray diffraction

IR Spectrography, HPLC, …

UC Davis: http://www.vetmed.ucdavis.edu/usal/index.cfmMinnesota Urolith Center: http://www.cvm.umn.edu/depts/minnesotaurolithcenter/Canadian veterinary urolith center: http://www.guelphlabservices.com/files/AHL/AHL%20Submission%20forms/urolith_submission_form_EN%2006_10.pdf

A problem of small dogsCanadian Veterinary urolith Center

Submissions 1998-2008

Breed effect - dogs

6,146,52

0

5

10

15

20

25

Miniature Schnauzers Labrador

Uni

t or

mL

/kg

pH Urine Vol. Micturition RSS CaOx

a b

a

a

a

b

bb

AE Stevenson, 2002

Breed panel composition will affect CaOx RSS

Urine supersaturationCrystal formation

P

O-

O-

O

O-

-

Mg +

+

+

+

Ca

Sulfate

CC

O

O

O

O

-

-

Citrate

Urine

CC

O

O

O

O

-

-

+

+Ca

Calcium Oxalate

Na+

K

+

Urinary pH and concentrations (mmol/l):

calcium, magnesium, sodium, potassium, phosphate, sulfate, ammonium, oxalate, citrate and

uric acid

Struvite and Calcium Oxalate Relative Supersaturation

(RSS)

Supersat®, Equil®

RSS Calculation

Ionic chromatography

(Dionex, Sunnyvale, CA, USA)

Cations methanesulfonic acidAnions KOH

RSS a tool to measure urine supersaturation and risk crystal formation

METASTABLE SUPERSATURATION

Spontaneous crystallization

Rapid crystal growth

UNDERSATURATION

LABILE SUPERSATURATION

Solubility product

No crystal dissolution

No crystallization

Crystal dissolution

Formation product

RSS

1

(71-99 mg/L)

CaOx 12

(900 mg/L)

MAP 2.5

How do we test the influence of the diet on RSS.

Adaptation (9 d) Collection (5 d)

Supersat®

RSS StruviteRSS CaOx

6-8 X

As of June 30, 2008 Feline diets: 341 dry diets

25 moist diets Canine diet: 53 dry diets

2881 urine samples28810 analyses

or

Titration pH =2-20°CChlorhexidine 20%

VolumeSG

To promote urine diuresis

Somme

0

10

20

30

40

50

60

70

80

Dry Dry Na Wet Wet Na

Moyenne volume u kg

type aliment

(689)

(95) (15) (33)

Dry

< 0,8% Na/DM

Dry

> 0,8% Na/DM

Wet

< 0,8% Na/DM

Wet

> 0,8% Na/DM

mL/kg/d

Reccurence of struvite stones

Struvite: Physiopathology (cats)

JP Cotard

JP Cotard

Concentratedurine Mg, NH4+, PO4Dry diet Nacl? Dietary fiber

pH > 6.5

Sulfur Aa Alkalizing minerals Alkaline tide

If pH < 6.5If diluted urine

Struvite: Physiopathology

•UTI Positive-urease bacteria Staphylococcus spp. (S.

Intermedius) Proteus Spp Antibiotherapy validated by urine

culture.

•Stérile: rare

Dogs

Avoid struvite reccurence (cats)

RSS struvite < 1

Dietary change

Urinary pH Precursors Diuresis

Acidifying diets• High in sulfur amino-acids

– Methionine, Cystine– Animal proteins, Corn gluten

• Low in alkalinizing minerals– CaCO3 ,...

• Use of acidifying mineral sources

– CaCl2, CaSO4, …

• Other acidifiers– Phosphoric Acid, NH4Cl,

Methionine

pH RSS Struvite < 1Time of dissolution

median 18 d (10-55 d)Dissolution and prévention

Acidifying diets

Houston et al BJN 2011

RSS struvite

Struvite stones: cumulative weight loss (%)

-100

-80

-60

-40

-20

0

0 5 10 15 20 25 30Number of days

cum

ulat

ed w

eigh

t los

s (%

)

-60

-50

-40

-30

-20

-10

0

0 1 2 3 4 5 6 7Number of days of dissolution process

cum

ulat

ed w

eigh

t los

s (%

) pH=6,32pH=6,47

Same pH but different RSS

RSS = 0.45

RSS=0,4

RSS=0,2

pH = 6.1

Same RSS but different pH

Avoid struvite reccurence (dogs)

• Disappearance of clinical signs < 10 d• Time of dissolution: 3 mo• No dissolution: - Antibio-resistance

- no struvite or mixed stones• ATBQ : 4 wks after disappearance of stones + control after Trt (7

d and 4 mo).• Acidifying diets

UTI

Antibiotics/ NSAID

↑ diuresis Urinary pH

No UTI

Dietary Manage-

ment

Reccurence of Calcium oxalate stones

Factors affecting CaOx RSS

Diets? pH urinaire

protein, Ca, P, Mg, Na, K, Cl

Protein level, sourceFiber level, source

Energy densityMineral bioavailabilityCalcium/Phosphorus

OxalateSodium

Vitamin DVitamin C, B6

….

Cats/dogsHypercalciuria

(HyperPTH, cushing, renal acidosis,

idiopathique, ..) Hyperoxaluria (chats)

Genetics/SizeOxalobacter

Promotors/ inhibitors

….

DiuresisCanned food

SodiumDietary fiber

….

JP Cotard

EnvironnementIndoorHeat

NeuteringStress

R2 = 0,0059

0

4

8

12

16

20

5,00 5,50 6,00 6,50 7,00 7,50 8,00

Urinary pH

CaO

x R

SS

Solubility product

Formation product

RSS CaOx

Individual data on 341 dry feline diets

Urinary pH does not allow to predict CaOx urine saturation

R2 = 0,3798

0

2

4

6

8

10

12

14

16

18

20

5,00 5,50 6,00 6,50 7,00 7,50 8,00

Urinary pH

Str

uvi

te R

SS

Urinary pH & RSS struviteIndividual data on 341 feline dry dietsRSS

Solubility Product

Dietary Sodium and high dietary moisture decreased Struvite and Calcium Oxalate RSS.0

2

4

6

8

10

0,0 0,5 1,0 1,5 2,0

RS

S s

tru

vite

Dry

Wet

0

5

10

15

20

0,0 0,5 1,0 1,5 2,0

Na alimentaire (g /100 g MS)

RSS

CaO

x

Dry

Wet

Cats: NaCl and RSS

Dietary Na (%/DM)

Formation Product

Usual level of Na in petfood

Stone-formers - dogs

(Stevenson et al, 2004)

Metabolic dysfunction

Treatments

Diet

diuresisWet food

NaClMictions

RSS CaOxOxalate, Vit C

Vit DCa/P

?urinary pH

Hyperparathyroidism

Cushing syndrome Renal acidosis

Low enzyme activity

(hyperoxaluria I or II)

Citrate deficiencyB6 deficiency

AvoidGlucocorticoids

Vitamin DVitamin C

Furosemide? Antibiotics Indicated

Hydrochloro-thiazidesK Citrate

Prevention of reccurrences CaOX

Regular check-upXrays - ultrasound post-op

Urinary sedimentsXrays or ultrasound follow-up

Endogenous purines

Dietary purines

PURINE BODY POOL:

Catabolism

synthesis salvage

degradation

Guanine

Hypoxanthine

Xanthine

Adenine

Uric acid

Allantoin

uricase

Uric acid

Allantoin

English Bulldog, Schnauzers,

Shih Tzu, Yorkshire

Allopurinol

Giesecke et al , J Nutr 1982, 112, 1822-1826Bannasch, 2004; Safra, 2005

SLC2A9

Urate stones

Urate stones

Stevenson et Rutgers, 2006

Medical management•Diet low in purines

Organ meat, fishes, poultry, cheese, yeast Soy isolate, wheat gluten, casein, egg, rice

•Diet moderate in protein10-18 % protein ammonium (metabolic acidosis – UTI)

•Alkalinizing dietpH = > 6.5 animal protein, sulfur amino-acidsSodium bicarbonate, K citrate

•Promote diuresis (SG=1.025)•Xanthine oxydase inhibitor

AllopurinolLow purine dietsDissolution 4-40 wks (moyenne = 14 wks)

JY Deschamps

Cystine stones

Stevenson et Rutgers, 2006

Medical management •Physiopathology

aa reabsorption in renal tubules Very low solubility of cystineHereditary - male

•Moderate to low protein diet10-18 % proteins – MET - CYSTaurine, carnitine supplementation

•Alkalinizing dietpH = ± 7.5Sodium bicarbonate, K Citrate

•Promote diuresis• N-(2mercaptopropionyl)-glycine (2-MPG)

Thiol groupsDiet low in methionine + cystineDissolution 1-3 mo

D Houston

Calcium phosphate stones

Stevenson et Rutgers, 2006

Medical management •Physiopathology

HyperparathyroïdismRenal tubular acidosisIdiopathic hypercalciuria? Severe UTI with very high pH

•4 mineral typesHydroxyapatite Ca10(PO4)6(OH)2 Brushite CaHPO42H2OCarbonate de calciumWhitlockite & octacalcium phosphate

•ManagementTreat the causeStimulate diuresispH 6-6.5Réduce dietary Ca/P , Vit D

Silica stones

Stevenson et Rutgers, 2006

Prevention of reccurence •Physiopathology

Urinary hyperexcretion of silica? Pica? Poor quality vegetable ingredients

•Management? Higher quality petfoodPromote diuresis

Houston

Conclusions

Diuresis + Urine dilution: RSS + Miction

+ Wet diet + NaCl + Promote water intake

Dietary management ++ Struvite (Cats ++, Dogs+) + Urate, cystine + CaOx ? (dilution, pH, other) ? Calcium phosphate, Silica

Reccurence + Confirm the occurrence of stone(s) + ? UTI + If struvite suspected: dissolution + Others: identification + trt + Follow-up

Animal + UTI (Struvite, urate) + Metabolism

(CaOx, urate, CaP) + Inhibitors

CrystallizationAgregation

Bibliography

• Wetropp J et al; Lower urinary tract disorders in cats. et Adams LG et al Canine ureteral and lower urinary tract diseases.

Textbook of Veterinary Internal Medicine 7th edition, 2010, Saunders, St Louis;

www.ivis.org

Thank you …Merci …ขอบคุ�ณคุรั�บObrigado …