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Urolithiasis

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Title: Urolithiasis


1
Urolithiasis
  • Stephen P. DiBartola, DVM
  • Department of Veterinary Clinical Sciences
  • College of Veterinary Medicine
  • Ohio State University
  • Columbus, OH 43210

The Nephronauts
2
Urolithiasis
  • Urine a complex aqueous solution of organic and
    inorganic solutes
  • 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
Urolithiasis
  • Urine is commonly supersaturated with
    crystalloids
  • Observation of individual crystal types in urine
    does not necessarily mean the patient is at risk
    for developing urolithiasis

4
Urolithiasis
  • Supersaturation (solubility product exceeded) of
    urine with a crystalloid depends on
  • Amount of solute ingested and excreted
  • Urine volume
  • Urine pH
  • Promoters
  • Inihibitors

5
General theories of urolithiasis
  • Precipitation-crystallization theory
  • Matrix-nucleation theory
  • Crystallization-inhibition theory
  • Some combination of the above?

6
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

7
Inhibitors of crystallization and aggregation
  • Pyrophosphates
  • Diphosphonates
  • Citrate
  • Some cations (e.g. Mg2)
  • Glycosaminoglycans
  • Nephrocalcin

8
Urolithiasis Naming of stones
  • When ?70 of the urolith is composed of one type
    of crystal it is named for the crystal
  • Mixed urolith lt 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

9
Prevalence of stone types
Stone type Dogs Cats
Number 77,190 20,343
Struvite 50 43
Oxalate 31 46
Urate 8 6
Cystine 1 lt 1
Silicate 1 lt 0.1
Calcium phosphate lt 1 lt 1
Data from University of Minnesota Stone
Laboratory 2000
10
Struvite urolithiasis
  • Most common stone type in dogs
  • Major crystalloid is MgNH4PO4H2O
  • Calcium phosphate also present in small amounts
    (2-10)

11
Struvite urolithiasis
  • Bladder is most common site in dogs and cats
  • High recurrence rate (gt 20)
  • Younger animals

12
Struvite urolithiasis
  • Struvite solubility decreases in alkaline urine
  • UTI with urease-positive bacteria (Staphylococci,
    Proteus spp) plays primary role in pathogenesis
    in dogs but not cats

13
Oxalate urolithiasis
  • Most common stone type in humans
  • Incidence in cats and (to a lesser extent) dogs
    has been increasing in the past 20 years

14
Oxalate urolithiasis
  • Composed of calcium oxalate monohydrate
    (whewellite) or calcium oxalate dihydrate
    (weddelite)
  • Frequently not detected by qualitative analysis

15
Oxalate urolithiasis
  • Most often in bladder in dogs
  • Kidneys, ureters, bladder in cats
  • May have jagged edges
  • UTI is a complication rather than predisposing
    factor
  • High recurrence rate (25 to 48)

16
Risk factors for oxalate urolithiasis in dogs
  • Age gt 4 years (highest risk between 8 and 12
    years of age)
  • Neutered male
  • Breeds miniature Schnauzer, Lhasa apso,
    Yorkshire terrier, Bichon frise, Shih tzu,
    miniature Poodle
  • Overweight
  • Pet dog vs working dog

17
Risk factors for oxalate urolithiasis in cats
  • Exclusive feeding of an acidifying diet
  • Middle-aged to older
  • Males (usually neutered) more commonly than
    females
  • Breeds Persian, Himalayan
  • Exclusive indoor environment

Increased incidence over past 20 years NOT
related to changes in age, breed, gender, or
reproductive status of cat population during this
time
18
Oxalate urolithiasis Pathogenesis
  • Derived from diet and endogenously from
    metabolism of ascorbic acid and glycine
  • In humans, increased dietary calcium or oxalate,
    increased GI absorption of calcium or oxalate, or
    inherited defects of oxalate metabolism may
    predispose to oxalate urolithiasis

19
Oxalate urolithiasis Pathogenesis
  • Altered calcium metabolism can result in
    increased urinary excretion of calcium
    (hypercalciuria)
  • Absorptive (GI) hypercalciuria
  • Some miniature Schnauzers (?)
  • Renal leak hypercalciuria
  • Resorptive (bone) hypercalciuria
  • Primary hyperparathyroidism
  • Chronic acidosis and acidifying diets (?)

20
Oxalate urolithiasis Other associations
  • Hyperadrenocorticism
  • Increased risk of calcium-containing stones
  • Decreased renal reabsorption of calcium?
  • Idiopathic hypercalcemia of cats

21
Idiopathic hypercalcemia of cats
  • 33 of cats with oxalate stones have
    hypercalcemia
  • Idiopathic hypercalcemia has become more common
    in cats in past 10 years and many have oxalate
    stones
  • Frequent history of acidifying diet
  • Hypercalcemia responds to high fiber diet or
    prednisone

22
Urate urolithiasis
  • Usually composed of ammonium acid urate in dogs
    (vs uric acid in humans)
  • Dalmatians and English bulldogs
  • Dogs with portosystemic shunts (often also
    contain struvite)

23
Urate urolithiasis
  • Males gt females
  • Bladder, urethra
  • UTI is a complicating rather than predisposing
    factor
  • High recurrence rate (30 to 50)

24
Urate urolithiasis
  • Defective uric acid metabolism in Dalmatian is
    a predisposing factor rather than primary cause

25
Urate urolithiasis
  • Urate derived from metabolism of purines
  • Converted to allantoin by dogs other than
    Dalmatians
  • Impaired transport of urate into hepatocytes not
    lack of uricase
  • Urate reabsorption decreased and secretion
    increased in Dalmatian kidney

26
Cystine urolithiasis
  • Uncommon in dogs rare in cats
  • Many breeds English bulldogs, Newfoundlands,
    Dachshunds, Irish terriers, Basset hounds
  • Almost exclusively males (except Newfoundlands)
  • Middle aged (4 to 6 years)

27
Cystine urolithiasis
  • Usually in bladder and urethra
  • UTI is a complicating rather than predisposing
    factor
  • High recurrence rate (47 to 75)
  • Cystinuria decreases in severity with age (gt 5
    years) in some affected dogs

28
Cystine urolithiasis
  • Cystinuria is an inherited defect in renal
    tubular transport of cystine or cystine and other
    amino acids (e.g. COLA group)
  • Cystine crystals are not normally found in urine

29
Cystinuria in Newfoundlands
  • Males and females - Autosomal recessive
  • Mutation in SLC3A1 gene (associated with type I
    cystinuria in humans)
  • Where tested in other breeds SLC3A1 gene not
    involved (non-type I cystinuria)

30
Silicate urolithiasis
  • Uncommon in dogs extremely rare in cats
  • Not detected by qualitative analysis
  • Often have jack-like appearance

31
Silicate urolithiasis
  • Diets high in corn gluten or soybean hulls may be
    contributory
  • Bladder and urethra
  • German shepherds, Old English sheepdogs, other
    breeds
  • Occasionally recur after surgery

32
Carbonate urolithiasis
  • Most common in horses
  • Rare in older male dogs
  • Not reported in cats
  • Calcium carbonate is less soluble in alkaline
    urine

33
History in urolithiasis
  • Struvite
  • Miniature Schnauzer, Bichon frise, Lhasa apso,
    Shih tzu, miniature Poodle
  • Female gt male
  • Generally younger
  • Oxalate
  • Miniature Schnauzer, Bichon frise, Lhasa apso,
    Shih tzu, Yorkshire terrier, miniature Poodle
  • Male gt female
  • Generally older

34
History in urolithiasis
  • Cystine
  • English bulldogs, Newfoundlands, Dachshunds,
    Irish terriers, Basset hounds, Bull Mastiffs,
    Rottweilers
  • Male gtgt female (except Newfoundland)
  • Young to middle-aged
  • Urate
  • Dalmatian, English bulldog
  • Male gt female
  • Middle-aged

35
History in urolithiasis
  • Silicate
  • German shepherd, Old English sheepdog
  • Male gt female
  • Middle-aged
  • Carbonate
  • Adult horses
  • No breed or sex predilection

36
History in urolithiasis
  • Depends upon
  • Anatomic location of uroliths
  • Duration of presence of uroliths
  • Physical features of uroliths
  • Presence or absence of UTI

37
History in urolithiasis
  • Kidney
  • No signs
  • Flank pain
  • Painless hematuria
  • Signs of infection
  • Signs of renal failure

38
History in urolithiasis
  • Ureter
  • No signs (especially cats)
  • Flank pain (acute ureteral obstruction)
  • Signs of post-renal azotemia (if bilateral or
    ureteral rupture)

39
History in urolithiasis
  • Bladder
  • No signs
  • Dysuria
  • Increased frequency
  • Hematuria

40
History in urolithiasis
  • Urethra
  • Signs of obstruction
  • Signs of post-renal azotemia
  • Dysuria
  • Increased frequency
  • Hematuria
  • No signs (uncommon)

41
Physical findings in urolithiasis depend
primarily on anatomic location of uroliths
42
Physical findings in urolithiasis
  • Kidney or ureter
  • Renomegaly if hydronephrosis or pyonephrosis
    present
  • Abdominal pain
  • No abnormal findings if kidneys not enlarged or
    palpable

43
Physical findings in urolithiasis
  • Bladder
  • Palpable stones
  • Thickened bladder wall

44
Physical findings in urolithiasis
  • Urethra
  • Large distended bladder suggestive of obstruction
  • Stone palpable on rectal or perineal exam

45
Laboratory findings in urolithiasis Urinalysis
  • Inflammatory sediment (pyuria, hematuria,
    proteinuria, bacteriuria)
  • Urine pH variable
  • Struvite Alkaline if urease-positive UTI
  • Cystine Acidic
  • Oxalate, urate, silicate Variable
  • Cystine crystals are abnormal other crystals
    are not diagnostic

46
Laboratory findings in urolithiasis Urine culture
  • Staph or Proteus in dogs with struvite
    urolithiasis and urease-positive UTI
  • Usually negative in cats with urolithiasis
  • UTI may complicate metabolic stone types
    (oxalate, urate, cystine, silicate)

47
Laboratory findings in urolithiasis Stone
analysis
  • Qualitative analysis NOT recommended
  • Xanthine and silicate not detected
  • Oxalate frequently not detected
  • False positive results for urate and cystine
  • Cannot tell which crystalloids are primary and
    which are secondary

48
Laboratory analysis in urolithiasis Stone
analysis
  • Use quantitative analysis (e.g. optical
    crystallography)
  • University of Minnesota
  • University of California, Davis
  • Commercial medical laboratories

49
Radiographic findings in urolithiasis
  • Most radiopaque
  • Calcium phosphate
  • Calcium oxalate
  • Silicate
  • Struvite
  • Cystine
  • Urate
  • Most radiolucent

Radiopacity will depend on how much calcium
phosphate is present

50
Urolithiasis General principles of management
  • Relief of urinary tract obstruction
  • Correction of fluid, electrolyte, and acid-base
    disturbances
  • Non-surgical retrieval of uroliths
  • Surgical removal of urolithis (if necessary)
  • Medical dissolution of uroliths
  • Preventive therapy

51
Urolithiasis ManagementRelief of obstruction
  • Passage of small diameter, well-lubricated
    catheter beyond urethral obstruction
  • Urohydropropulsion
  • Decompression by cystocentesis
  • Emergency urethrotomy

52
Urolithiasis Nonsurgical removal of
urolithsVoiding urohydropropulsion
  • Stones must be small
  • lt 7 mm in female dog
  • lt 5 mm in male dog or
  • female cat
  • General anesthesia
  • Distend bladder with saline via cystoscope
  • Radiograph afterward

From Lulich JP et al. JAVMA 203660, 1993.
53
Urolithiasis Nonsurgical removal of
urolithsCatheter-assisted retrieval of uroliths
  • Small stones can be collected from male dog for
    quantitative analysis

From Lulich JP et al. JAVMA 201111, 1992.
54
Urolithiasis Nonsurgical removal of
urolithsLithotripsy
  • 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
55
Urolithiasis Medical dissolution of uroliths
  • Protocols devised for struvite, urate, and
    cystine
  • No effect protocol for oxalate yet

56
Urolithiasis General principles of
managementInduction of polyuria with NaCl
  • Aim to decrease USG to lt 1.025 (decreased
    concentration of crystalloids)
  • Allow animal to void 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

57
Urolithiasis General principles of
managementEradication 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

58
Struvite urolithiasisMedical management
  • Eliminate UTI
  • If urine pH still alkaline search for another
    reason
  • Diet
  • Metabolic (e.g. distal RTA)
  • Calculolytic diet

59
Struvite urolithiasisCalculolytic diet (S/d)
  • Low in phosphorus and magnesium
  • High in NaCl
  • Canine product low in protein to reduce urea
    availability to urease-positive bacteria

60
Struvite urolithiasisCalculolytic 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

61
Struvite urolithiasisCalculolytic diet (S/d)
  • Is is struvite?
  • Urease-positive UTI
  • Alkalkine urine
  • Struvite crystalluria
  • Radiodense calculus

?
62
Struvite urolithiasisCalculolytic diet (Feline
S/d)
  • Similar to Canine S/d but not protein-restricted
  • Average time for dissolution for sterile struvite
    stones 30 days
  • Success rate gt 90
  • Dont add acidifier!

63
Oxalate urolithiasisMedical 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

64
Oxalate urolithiasisMedical 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

65
Urate urolithiasisMedical 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

66
Urate urolithiasisMedical 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
67
Urate urolithiasisMedical management 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

68
Urate urolithiasisMedical management U/d Diet
for dissolution and 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?)

69
Urate urolithiasisMedical management U/d 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
70
Urate urolithiasisMedical management U/d Diet
  • Client compliance indicated by
  • Disappearance of urate crystals from sediment
  • BUN lt 10 mg/dl
  • USG lt 1.020
  • Urine pH gt 7.0
  • Results
  • Complete dissolution 33
  • Partial dissolution 33
  • No dissolution 33
  • Time to dissolution
  • 1 to 10 mos
  • Average 3 to 4 mos

71
Urate urolithiasisPrevention
  • 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

72
Cystine urolithiasisMedical 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

73
Cystine urolithiasis Medical management2-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

74
Cystine urolithiasisDissolution 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

75
Cystine urolithiasisPrevention 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
76
Cystine urolithiasisAlkalinization
  • 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

77
Cystine urolithiasisDietary 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

78
Silicate urolithiasisMedical 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 ?

79
Carbonate urolithiasisMedical 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

80
UrolithiasisComplications
  • 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
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