Urolithiasis

Question 1

ACVIM consensus for ureterolith management in cats vs dogs

Answer 1

Obstructive ureteroliths in cats should be managed by subcutaneous ureteral bypass or ureteral stenting
first choice for the best possible outcome
Do not recommend medical dissolution

Recommendation 2.9: Obstructive ureteroliths in dogs should be managed by ureteral stenting

+- combined with subsequent extracorporeal shockwave lithotripsy if necessary.

Ureteral stents are associated with the lowest short- and long-term morbidity and mortality rates
when compared to all other reported treatments
Recommendation 2.11: Routinely culture urine of dogs with ureteral obstruction and consider antimicrobial treatment
59% of dogs UTI
30% pyonephrosis and sepsis

Question 2

Broad risk factors for urolith development

Answer 2

Sequelae to multiple interacting abnormalities
Can be compound uroliths when > 1 different layer present

Risk Factors:
Urinary saturation of components
Presence of inhibitors of urolithiasis - nephrocalcin, uropontin, Tamm-Horsfall mucoprotein
Urinary pH
Saturation of ions in solution
- Metastable = neither formation or dissolution
- Undersaturation → dissolution
- Labile supersaturation → formation

Homogeneous nucleation: form straight from crystals due to supersaturation
Epitaxial growth: starts on existing surfaces.

Question 3

Recent publications in trends of urolith type in dogs and cats

Answer 3

JVIM 2021- trends in urolith composition from UC Davis in DOGS
→ Ca-ox and struvite most common, 47% and 43%
→ OVerall proportion of Ca-ox uroliths in dogs has decreased by 8% since 2006 survey,.
→ Cystine containing uroliths increased to 2.7% compared to 1.4%

JVIM 2021 - trends in cats:
→ decrease in Ca-ox proportion 50 → 37% though still accounted for greater proportion of UUT stones.
→ increased proportion of struvite 41 → 54%

Question 4

Stone types where medical dissolution should be considered for cystoliths

Answer 4

Struvite - always

Urate - if not hepatic disease

Cysteine - dogs but maybe not cats

Urocystoliths with CS should be removed by minimally invasive techniques, in absence of clinical signs rapid removal is not necessary
- only problematic nephroliths require Tx

Question 5

Recommendations for retrieval of uroliths

Answer 5

Voiding urohydropulsion - female dogs or cats with small enough uroliths.
Basket retrieval - could be quite traumatic and risk introduction of infection if multiple stones.
Intracorporeal laser lithotripsy - limited availability, patient must be big enough to allow passage of fragments
Extracorporeal lithotripsy - also limited availability
Percutaneous cystolithotomy (less invasive than cystotomy) preferred over cystotomy.

Incision-less procedures are assoc with lower morbidity and shorter hospitalisation. Suture nidus contributed to 9% of recurrence in one study

Urethral surgery is discouraged by ACVIM consensus

Question 6

Comparison studies for PCCL and cystostomy in dogs and cats

Answer 6

JVIM 2022 - comparison of cystotomy to PCCL for 81 cases. PCCL had shorter hospitalisation time (same day procedure) for dogs but not cats.

JFMS 2022 - 28 cats, comparison of PCCL to cystotomy. 8x greater risk of composite outcome in the open surgery group.
Procedural cost higher for minimally invasive.

Question 7

Non-invasive removal options for uroliths

Answer 7

Voiding urohydropulsion - female dogs or cats with small enough uroliths.
Basket retrieval - could be quite traumatic and risk introduction of infection if multiple stones.
Intracorporeal laser lithotripsy - limited availability, patient must be big enough to allow passage of fragments
Extracorporeal lithotripsy - also limited availability
Percutaneous cystolithotomy (less invasive than cystotomy) preferred over cystotomy.

Incision-less procedures are assoc with lower morbidity and shorter hospitalisation. Suture nidus contributed to 9% of recurrence in one study

Percutaneous cystotomy pigtail catheter - urinary diversion for obstruction while awaiting definitive treatment. 40% complication rate in recent study

Question 8

Struvite - pathogenesis difference in dogs vs cats

Recommended Dissolutions

Answer 8

Dogs - more often females with urease producing bact
-> Tx UTI, low Mg and PO4, dilute and acidify urine
Long term prevention in dogs is about addressing risk of recurrent infection

Cats (and pugs) - sterile in most cases, poorly understood pathophys.
Imbalance b/w promotors and inhibitors

In the absence of LUTI medical dissolution with diet (low protein, low Mg, LOW pH), urine acidification and urine dilution can be sufficient

continue for 4 weeks beyond dissolution

Question 9

Controversy of ABx in struvite dissolution

Answer 9

ISCAID no consensus on if needed for duration of dissolution (due to release of bact) or if this is unlikely to contribute to reformation/symptoms.
→ study where only 7 days of ABx given in 12 dogs reported no relapse of infection
JVIM 2021 - Minnesota Uni study of medical dissolution using hill’s s/d. 87% dogs with UTI
58% complete dissolution, urine pH not different between successful and unsuccessful groups. Duration of ABx longer in the success group - though ⅔ of successful patients had discontinued ABx before complete resolution (or before imaging so cannot be sure given retrospective design).

Question 10

causes of urate urolithiasis in dogs - and recommended Tx/prevention

Answer 10

inherited urate transporter deficiency
→ hyperuricosuria due to inefficient transport of uric acid into hepatocytes and proximal tubular cells
Recommendation 3.4: to Minimize Urate Urolith Recurrence, Decrease Urine Concentration, Promote Alkaline Urine, and Limit Purine Intake

Liver dysfunction/Shunt
Reduced ammonia to urea
Reduced uric acid → allantoin = both pathways are affected
Dissolution often occurs w surgery, but no study to show how frequently this occurs

Question 11

Pathogenesis theories for ca-ox uroliths in dogs and cats

Recommended Tx/Prevention

Answer 11

Breeds: Min Schnauzer, Griffon, Shih Tzu, Yorkshire, Maltese, Bichon

→ higher uCa excretion than other dogs (but same level of oxalate)
Driven by hypercalciuria → investigate for hypercalcaemia

relative supersaturation of urine with calculogenic substances (Ca and ox) as well as imbalance of promoting and inhibiting substances (Mg, pyrophosphates)

To minimize calcium oxalate urolith recurrence, decrease urine concentration - high moisture foods aim for USG <1.020/1.030 cats, avoid urine acidification, and avoid diets with excessive protein content

Feeding high-sodium dry foods should not be recommended as a substitute for high-moisture foods

Question 12

Possible associated factors for Ca-ox uroliths

Answer 12

Associative findings have not been proven to correlate with disease development in dogs

JVIM 2022 - 3.3x increased risk of Ca-ox uroliths in dogs with hyperTG (not including Schnauzers). Similar assoc reported in humans with metabolic syndrome.
JVIM 2020 - uCa:Cr ratio was higher in stone forming Min Schnauzers compared to controls.
JVIM 2022 - Microbiome of Ca-ox urolith dogs had more Acinetobacter than controls
JVIM 2021 - mutations in Vit D receptor have been reported in dogs with Ca-ox, but Vit D levels are not different b/w cases and controls

Question 13

Why are effective preventative Tx for Ca-ox difficult

Answer 13

(1) properly designed clinical trials evaluating urolith recurrence have not been published,

(2) the exact mechanisms underlying calcium oxalate urolith formation are not completely understood,

(3) associative factors identified in epidemiological studies have not been proven to result in disease, and

(4) surrogate endpoints of therapeutic efficacy such as relative supersaturation are mathematical models that may not correlate well with calcium oxalate urolith

Question 14

Adjunctive Tx if diets dont prevent Ca-ox uroliths

Answer 14

K-citrate - alkalinise urine but citrates are also inhibitor of Ca-ox formation because citrate can bind and chelate the Ca.

Thiazide diuretics - reduce supersaturation, inhibit distal tubule NaCl transporter → increased Ca reabsorption

Up to 50% recurrence rate within 2 years in DOGS
7% recurrence in cats within 5 years

Question 15

Allopurinol MOA

Answer 15

inhibits xanthine oxidase (requires hepatic conversion to active metabolite) → inhibition of conversion of oxypurines to uric acid
Dose required to do this and NOT cause xanthine urolith production varies b/w dogs. Depends on severity of disease, purine levels in diet and endogenous purine production

AE - xanthine uroliths

Question 16

Cause of cysteine uroliths in dogs and cats (and concurrent clinical findings and why)

Recommended Tx

Answer 16

Dogs: mutations in proximal tubule transporters for non-essential amino acids.
Labrador, Newfy - autosomal recessive
English BD, French BD, Mastiff - unrelated mutation
COLA lost in dogs = cystine, ornithine, lysine, arginine

Cats: very rare, a mutation in proximal tubular transporter is reported that is hereditary. Often very young at onset, DSH or Siamese.
Concurrent signs of hypersalivation, lethargy, seizures due to hyperammonaemia from impaired intestinal absorption of cystine and other essential a.as
→ can develop arginine deficiency → urea cycle deficiency and hyperammonaemia.

Androgen dependence is reported in some dogs and cats, and explains the high prevalence in male dogs. In such cases neutering is curative - but this is not all.

Dogs: increased water consumption, limit sulfur containing a.a intake.
Thiol drugs (2 MPG) - binds to cysteine in urine making it more soluble
Cats: non-acidifying canned food, no controlled studies for preventing recurrence.

ACVIM consensus: To Minimize Cystine Urolith Recurrence, Decrease Urine Concentration, Limit Animal Protein Intake (reduce cysteine precursors like methionine), Limit Sodium Intake, Increase Urine PH, and Neuter.

Ensure adequate taurine and carnitine in diet - as deficiencies can occur

Question 17

Cuases of LUT obstruction in cats vs dogs

Answer 17

Urolithiasis most common in dogs

Urethral plugs (crystalline) in cats is most common
→ mucus, inflammatory protein, varying mineral and blood or sloughed tissue.
Functional obstruction reported in cats - urethral spasm and oedema +/- concurrent plug.

Urethral stricture - can be congenital stenosis but more often secondary to trauma from ucath or stone.
Bladder/urethral neoplasia
Prostatic disease - neoplasia, BPH, infection, cysts

Question 18

Pathogenesis of post-obstructive diuresis

Answer 18

A result of accumulation of osmotically active substances in blood → osmotic diuresis

Tubular epithelial dysfunction following
AKI

Medullary washout

ADH resistance
Increased natriuretic substances due to obstruct

Question 19

Arguments for and against decompressive cysto in UO and evidence

Answer 19

Cystocentesis decompression- can help reduce pressure prior to ucath placement, and more rapid resumption of GFR. Risk of inducing rupture if severely devitalised bladder wall (reportedly uncommon in recent study in 45 cats).
JAVMA 2021 - decompression did not improve ability to pass ucath but also not associated with increase in abdominal effusion.

Question 20

The prazosin debate in UO evidence for and against

Answer 20

lack of evidence for efficacy particularly long term. Affect PREPROSTATIC urethral tone but not post-prostatic (skeletal muscle) which is where most obstructions occur.
JFMS 2021 - random control trial of prazosin post-obstruction in 65 cats
→ no significant difference in obstruction rate compared to placebo
JAVMA 2022 - retrospective study of 302 cats getting prazosin cf 86 did not. Other mgmt of UO the same
→ prazosin group did not reduce risk of rUO prior to discharge 11% cf no Tx group 5.8%. This was more significant within the first 14d 23% vs 13%
→ As observational retro study may have been risk of bias for more severe cats getting prazosin or other clinical factors.
→ lack of standardised Tx protocols for cats
→ potential for multiple confounding factors affecting data

Question 21

Outcomes reported for perineal urethrostomy for UO in cats - 3 recent studies

Answer 21

JFMS 2020 - long term follow up in 74 cases, owner survey of QoL reported excellent in 75%, and no responses <7/10
JFMS 2020 - clinical outcome in 28 cats, amount of LUTI and dermatitis was less for PU than PPU. PU had 82% owner satisfaction compared to 30% for PPU
JFMS 2022 - transpelvic urethrostomy, 18% short term complication rate, 34% long term (FIC, UTI and stenosis), 82% owner satisfaction. 89% reported QoL good to very good.

Question 22

Indications for urethral stent (3)

Answer 22

Urethral obstruction due to transitional cell carcinoma, prostatic carcinoma,leiomyoma, or other neoplastic conditions of the urethra
–> only develop UO in about 10% of cases
–> Dogs with a very poor urine stream that still empty likely have a partial obstruction and urethral stent placement should be considered

External urethral compression secondary to metastatic intrapelvic lymphadenopathy

Benign urethral obstruction associated with previous urethral trauma (includingiatrogenic), previous surgery, reflex dyssynergia, and proliferative urethritis.