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Dietary management of (reccurent) urolithiasis.

Dietary management of (reccurent) urolithiasis. V. Biourge, DVM PhD Dip ACVN&ECVCN Royal Canin, Centre de Recherche, Aimargues (France). Plan. Lower urinary tract diseases (LUTD) Work-up of reccurent urolithiasis Urinary stones How to determine their composition ? Urinary Supersaturation

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Dietary management of (reccurent) urolithiasis.

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  1. Dietary management of (reccurent) urolithiasis. V. Biourge, DVM PhD Dip ACVN&ECVCN Royal Canin, Centre de Recherche, Aimargues (France)

  2. 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.

  3. LUTD: definition • LUTD • Syndrome • Frequent urination: pollakiuria • Painful urination: dysuria • Blood in urine: hematuria • Urination outside litter box: periuria • Urethral blockade Buffington Dr. Rosama Pusoonthornthum

  4. LUTD

  5. LUTD: older cats • Most frequent causes • 81 cats > 10 yr with hematuria and dysuria • UTI ................................... 46 % • Urolith + UTI ................... 17 % • Uroliths ............................. 10 % • Urethral plugs ................... 7 % • Trauma ............................. 5 % • Idiopathic........................... 5 % • Bartges, 1997

  6. 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, … Reccurence of LUTDs Cystine CVUC

  7. 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

  8. 40-45% 40-45% 6-15% <0.01 %Cn-Ct 0.01-2 %Cn < 0.01 %Cn 0.6 Ct-5Cn % Urinary stones Struvite Urate Calcium oxalate Courtesy of Dr Buffington Courtesy of Dr Deschamps Xanthine Cystine Silica Phosphate de Ca CVUC WCPN

  9. Simple Vs mixed stones Simple One major mineral (>70%) Mineral = 100% 61-87 % of stones Mixed stones < 70 % Nidus Struvite CaOx CVUC

  10. Urinary stone composition CVUC

  11. Urinary stone composition CVUC

  12. Urinary stone composition X-ray diffraction Optical crystallography IR Spectrography, HPLC, … UC Davis: http://www.vetmed.ucdavis.edu/usal/index.cfm Minnesota 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

  13. A problem of small dogs Canadian Veterinary urolith Center Submissions 1998-2008

  14. b a b a a b b a Breed effect - dogs  Breed panel composition will affect CaOx RSS AE Stevenson, 2002

  15. + - Ca O + - Na O C O C + + Ca O + + - Mg + K O- P O- O- + O - Calcium Oxalate O - O C O C O Sulfate Urine supersaturation Citrate Crystal formation Urine

  16. RSS Calculation Urinary pH and concentrations (mmol/l): calcium, magnesium, sodium, potassium, phosphate, sulfate, ammonium, oxalate, citrate and uric acid Supersat®, Equil® Ionic chromatography (Dionex, Sunnyvale, CA, USA) Struvite and Calcium Oxalate Relative Supersaturation (RSS) Cations methanesulfonic acid Anions  KOH

  17. RSS a tool to measure urine supersaturation and risk crystal formation RSS LABILE SUPERSATURATION Spontaneous crystallization Rapid crystal growth (71-99 mg/L) CaOx 12 Formationproduct (900 mg/L) MAP 2.5 METASTABLE SUPERSATURATION No crystal dissolution 1 Solubility product UNDERSATURATION No crystallization Crystal dissolution

  18. How do we test the influence of the diet on RSS. 6-8 X or Supersat® Adaptation (9 d) Collection (5 d) RSS Struvite RSS CaOx Titration pH =2 -20°C Chlorhexidine 20% Volume SG As of June 30, 2008 Feline diets: 341 dry diets 25 moist diets Canine diet: 53 dry diets 2881 urine samples 28810 analyses

  19. (95) (15) (33) (689) To promote urine diuresis mL/kg/d Dry < 0,8% Na/DM Dry > 0,8% Na/DM Wet < 0,8% Na/DM Wet > 0,8% Na/DM

  20. Reccurence of struvite stones

  21. If pH < 6.5 If diluted urine Struvite: Physiopathology (cats) pH > 6.5  Sulfur Aa Alkalizing minerals Alkaline tide • Concentrated • urine • Mg, NH4+, PO4 Dry diet Nacl ? Dietary fiber JP Cotard JP Cotard

  22. Struvite: Physiopathology • UTI • Positive-urease bacteria • Staphylococcus spp. (S. Intermedius) • Proteus Spp • Antibiotherapy validated by urine culture. • Stérile: rare Dogs

  23. Avoid struvite reccurence (cats) Dietary change Urinary pH Precursors Diuresis RSS struvite < 1

  24. Acidifying diets 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 < 1 • Time of dissolution median 18 d (10-55 d) • Dissolution and prévention Houston et al BJN 2011

  25. RSS struvite Struvite stones: cumulative weight loss (%) Same RSS but different pH Same pH but different RSS RSS=0,4 RSS=0,2 RSS = 0.45 pH = 6.1

  26. Avoid struvite reccurence (dogs) UTI No UTI ↑ diuresis Urinary pH Antibiotics/ NSAID Dietary Manage-ment • 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

  27. Reccurence of Calcium oxalate stones

  28. Factors affecting CaOx RSS Diets ? pH urinaire protein, Ca, P, Mg, Na, K, Cl Protein level, source Fiber level, source Energy density Mineral bioavailability Calcium/Phosphorus Oxalate Sodium Vitamin D Vitamin C, B6 …. Cats/dogs Hypercalciuria (HyperPTH, cushing, renal acidosis, idiopathique, ..) Hyperoxaluria (chats) Genetics/Size Oxalobacter Promotors/ inhibitors …. JP Cotard Diuresis Cannedfood Sodium Dietaryfiber …. Environnement Indoor Heat Neutering Stress

  29. RSS CaOx Urinary pH does not allow to predict CaOx urine saturation Individual data on 341 dry feline diets Formation product Solubility product

  30. Urinary pH & RSS struvite Solubility Product Individual data on 341 feline dry diets RSS

  31. Usual level of Na in petfood Cats: NaCl and RSS Dietary Sodium and high dietary moisture decreased Struvite and Calcium Oxalate RSS. Formation Product Dietary Na (%/DM)

  32. Stone-formers - dogs (Stevenson et al, 2004)

  33. Treatments Metabolic dysfunction  RSS CaOx Oxalate, Vit C Vit D Ca/P ?urinary pH Prevention of reccurrences CaOX Avoid Glucocorticoids Vitamin D Vitamin C Furosemide ? Antibiotics Indicated Hydrochloro-thiazides K Citrate Hyperparathyroidism Cushing syndrome Renal acidosis Low enzyme activity (hyperoxaluria I or II) Citrate deficiency B6 deficiency Regular check-up Xrays - ultrasound post-op Urinary sediments Xrays or ultrasound follow-up Diet diuresis Wet food NaCl Mictions

  34. Urate stones Hypoxanthine Xanthine Allopurinol Allantoin Allantoin Uric acid Uric acid English Bulldog, Schnauzers, Shih Tzu, Yorkshire uricase Endogenous purines Dietary purines synthesis salvage PURINE BODY POOL: degradation SLC2A9 Catabolism Guanine Adenine Bannasch, 2004; Safra, 2005 Giesecke et al , J Nutr 1982, 112, 1822-1826

  35. Urate stones • Medical management • Diet low in purines • Organ meat, fishes, poultry, cheese, yeast • Soy isolate, wheat gluten, casein, egg, rice • Diet moderate in protein • 10-18 % protein •  ammonium (metabolic acidosis – UTI) • Alkalinizing diet • pH = > 6.5 •  animal protein, sulfur amino-acids • Sodium bicarbonate, K citrate • Promote diuresis (SG=1.025) • Xanthine oxydase inhibitor • Allopurinol • Low purine diets • Dissolution 4-40 wks (moyenne = 14 wks) JY Deschamps Stevenson et Rutgers, 2006

  36. Cystine stones • Medical management • Physiopathology • aa reabsorption in renal tubules • Very low solubility of cystine • Hereditary - male • Moderate to low protein diet • 10-18 % proteins – MET - CYS • Taurine, carnitine supplementation • Alkalinizing diet • pH = ± 7.5 • Sodium bicarbonate, K Citrate • Promote diuresis • N-(2mercaptopropionyl)-glycine (2-MPG) • Thiol groups • Diet low in methionine + cystine • Dissolution 1-3 mo D Houston Stevenson et Rutgers, 2006

  37. Calcium phosphate stones • Medical management • Physiopathology • Hyperparathyroïdism • Renal tubular acidosis • Idiopathic hypercalciuria • ? Severe UTI with very high pH • 4 mineral types • Hydroxyapatite Ca10(PO4)6(OH)2 • Brushite CaHPO42H2O • Carbonate de calcium • Whitlockite & octacalcium phosphate • Management • Treat the cause • Stimulate diuresis • pH 6-6.5 • Réduce dietary Ca/P , Vit D Stevenson et Rutgers, 2006

  38. Silica stones • Prevention of reccurence • Physiopathology • Urinary hyperexcretion of silica • ? Pica • ? Poor quality vegetable ingredients • Management • ? Higher quality petfood • Promote diuresis Stevenson et Rutgers, 2006 Houston

  39. Reccurence + Confirm the occurrence of stone(s) + ? UTI + If struvite suspected: dissolution + Others: identification + trt + Follow-up Diuresis + Urine dilution: RSS + Miction + Wet diet + NaCl + Promote water intake Conclusions Animal + UTI (Struvite, urate) + Metabolism (CaOx, urate, CaP) + Inhibitors Crystallization Agregation Dietary management ++ Struvite (Cats ++, Dogs+) + Urate, cystine + CaOx ? (dilution, pH, other) ? Calcium phosphate, Silica

  40. Bibliography • Wetropp Jet al; Lower urinary tract disorders in cats. et Adams LG et al Canine ureteral and lower urinary tract diseases. Textbookof VeterinaryInternalMedicine 7thedition, 2010, Saunders, St Louis; www.ivis.org

  41. Thank you … Merci … ขอบคุณครับ Obrigado …

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