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Basics ⬇

Basics

Definition

Appearance of crystals in urine

Pathophysiology

  • Crystals form only in urine that is, or recently has been, supersaturated with crystallogenic substances; thus crystalluria represents a risk factor for urolithiasis. However, detection of urine crystals is not synonymous with uroliths and clinical signs associated with them, nor is detection of urine crystals irrefutable evidence of a stone-forming tendency.
  • Certain crystal types such as cystine, urate, or 2,8-dihydroxyadenine may indicate an underlying disease. Proper identification and interpretation of urine crystals is important in formulation of medical protocols to dissolve uroliths. Evaluation of urine crystals may aid in (1) detection of disorders predisposing animals to urolith formation, (2) estimation of the mineral composition of uroliths, and (3) evaluation of the effectiveness of medical protocols initiated to dissolve or prevent uroliths.
  • Crystalluria in individuals with anatomically and functionally normal urinary tracts is usually harmless because the crystals are eliminated before they grow large enough to interfere with normal urinary function. However, they represent a risk factor for urolithiasis.
  • Crystals that form following elimination or removal of urine from the patient often are of little clinical importance. Identification of crystals that have formed in vitro does not justify therapy. In recent studies following time and temperature changes, crystals formed in 28% of dog and cat samples that were initially free of crystals.
  • Detection of some types of crystals (e.g., cystine and ammonium urate) in clinically asymptomatic patients, frequent detection of large aggregates of crystals (e.g., calcium oxalate or magnesium ammonium phosphate) in apparently normal individuals, or detection of any form of crystals in fresh urine collected from patients with confirmed urolithiasis may have diagnostic, prognostic, or therapeutic importance.
  • Drug crystals detected in patients being administered high doses of medications such as allopurinol, sulfadiazines, or fluoroquinolones may prompt a change in therapy as they are a risk factor for formation of drug-containing uroliths.

Systems Affected

Renal/Urologic

Signalment

  • Calcium oxalate in miniature schnauzer, Yorkshire terrier, Lhasa apso, and miniature poodle dogs, and Burmese, Himalayan, and Persian cats.
  • Cystine in dachshunds, English bulldogs, Newfoundlands, and others.
  • Ammonium urate in Dalmatians and English bulldogs.
  • Struvite in any breed of dog with a concomitant urinary tract infection.
  • Struvite in cats and ferrets is not typically associated with urinary tract infections.
  • Xanthine in Cavalier King Charles spaniels.
  • 2,8-dihydroxyadenine in Native American Indian dogs and wolves.

Signs

None, or those caused by concomitant urolithiasis.

Causes

In Vivo Variables

  • Concentration of crystallogenic substances in urine (which in turn is influenced by their rate of excretion and urine concentration of water).
  • Urine pH (struvite and calcium phosphate are most common in neutral-to-alkaline urine; ammonium urate, sodium urate, calcium oxalate, cystine, and xanthine crystals are most common in acid-to-neutral urine).
  • Solubility of crystallogenic substances in urine.
  • Excretion of diagnostic agents (e.g., radiopaque contrast agents) and medications (e.g., sulfonamides).
  • Dietary influence-hospital diet may differ from home diet; timing of sample collection (fasting vs. post-prandial) may influence evidence of crystalluria.

In Vitro Variables

  • Temperature.
  • Evaporation.
  • pH changes following sample collection.
  • Technique of specimen preparation-centrifugation versus non-centrifugation, volume of urine examined.
  • Important in vitro changes that occur following urine collection may enhance formation or dissolution of crystals. When knowledge of in vivo urine crystal type and quantity is especially important, examine fresh specimens, ideally at body temperature. If this is not possible, they should be at room temperature, not refrigeration temperature.
  • Collection container-spurious crystals may be contaminants from unclean collection containers.

Risk Factors

See preceding discussion about in vivo and in vitro variables in crystalluria.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

Ammonium Urate, Sodium Urate, and Amorphous Urate Crystalluria

  • Uncommonly observed in apparently healthy dogs and cats.
  • Frequently observed in dogs and occasionally observed in cats with portal vascular anomalies, with or without concomitant ammonium urate uroliths.
  • Observed in some dogs and cats with urate uroliths caused by disorders other than portal vascular anomalies such as canine breeds identified as carriers of the hyperuricosuria gene.

Bilirubin Crystalluria

  • Observed in highly concentrated urine from some healthy dogs.
  • Large numbers in serial samples should arouse suspicion of an abnormality in bilirubin metabolism.
  • Usually associated with underlying diseases in cats.

Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate Crystalluria

  • May be observed in apparently healthy dogs and cats and in dogs and cats with uroliths primarily composed of calcium oxalate.
  • Calcium oxalate monohydrate crystals are most commonly associated with ethylene glycol toxicity, but calcium oxalate dihydrate may be observed, or ethylene glycol toxicity may also occur without crystalluria.

Calcium Phosphate Crystalluria

  • Large numbers of crystals presumed to be composed of calcium phosphate have been observed in apparently healthy dogs, dogs with persistently alkaline urine, dogs with calcium phosphate uroliths, and dogs with uroliths composed of a mixture of calcium phosphate and calcium oxalate.
  • Small numbers of calcium phosphate crystals may occur in association with infection-induced struvite crystalluria.
  • May be observed in dogs and cats with primary hyperparathyroidism, and renal tubular acidosis.

Cystine Crystalluria

Observed in dogs and cats with inborn errors of metabolism characterized by abnormal transport of cystine and other dibasic aminoacids.

Struvite Crystalluria

  • Observed in dogs and cats that are apparently healthy.
  • Observed in dogs and cats with infection-induced struvite uroliths, sterile struvite uroliths, non-struvite uroliths, and uroliths of mixed composition (e.g., a nucleus composed of calcium oxalate and a shell composed of struvite).
  • Observed in dogs and cats with urinary tract disease without uroliths.

Uric Acid Crystalluria

  • Uncommon in dogs and cats.
  • Importance as described for ammonium and amorphous urates.

Xanthine Crystalluria

  • Suggests administration of excessive dosages of allopurinol in conjunction with consumption of relatively high amounts of dietary purine precursors.
  • Primary xanthinuria has been observed in Cavalier King Charles spaniels.
  • Primary xanthinuria and xanthine uroliths occur in cats.

Miscellaneous Crystalluria

  • Cholesterol crystals-observed in humans with excessive tissue destruction, nephrotic syndrome, and chyluria; observed in apparently healthy dogs.
  • Hippuric acid crystals-apparently rare in dogs and cats; importance unknown.
  • Leucine crystals in dogs-importance not determined; may occur in association with cystinuria.
  • Tyrosine crystals-occur in association with severe liver disease in humans; uncommonly observed in dogs and cats with liver disorders. Sodium urate needle-like appearance commonly misinterpreted as tyrosine needles.
  • 2,8-dihydroxyadenine- is a genetic disorder, the result of a metabolic abnormality due to the deficiency of the enzyme, adenine phosphoribosyl transferase (APRT).

Drug-Induced Crystalluria

  • May be observed following administration of radiopaque contrast agents.
  • May be observed following treatment with sulfadiazine, fluoroquinolones, primidone, xanthine oxidase inhibitors, and tetracycline.

Laboratory Findings

Drugs That May Alter Laboratory Results

Disorders That May Alter Laboratory Results

N/A

Valid if Run in Human Laboratory?

Yes

CBC/Biochemistry/Urinalysis

  • Bilirubin crystals may be associated with bilirubinemia and other laboratory abnormalities of hepatic disorders.
  • Most dogs and cats with calcium oxalate and calcium phosphate crystalluria are normocalcemic; some are hypercalcemic.
  • Some dogs and cats with calcium oxalate crystalluria may be acidemic.
  • Serially examine fresh specimens when knowledge of in vivo urine crystal type is especially important; evaluate the number, size, and structure of crystals and their tendency to aggregate.
  • Microscopic evaluation of the appearance of urine crystals gives only a tentative indication of their composition; variable conditions associated with their formation, growth, and dissolution may alter their appearance. Definitive identification of crystal composition depends on one or more of these techniques: optical crystallography, infrared spectroscopy, X-ray diffraction, and electron microprobe analysis.

Other Laboratory Tests

  • Cystine crystalluria is usually associated with a positive urine cyanide-nitroprusside reaction.
  • Sulfonamide crystalluria may be associated with a positive lignin test.
  • Ammonium urate and amorphous urate crystals are insoluble in acetic acid; addition of 10% acetic acid to urine sediment containing these crystals often yields uric acid and sometimes sodium urate crystals.
  • Most dogs and a few cats with struvite crystalluria have urinary tract infections caused by urease-producing bacteria (especially staphylococci and sometimes Proteus spp.).
  • Dogs and cats with ammonium urate crystalluria and portosystemic shunts often have high serum bile acid levels and hyperammonemia.
  • Dogs and cats with calcium oxalate crystalluria secondary to ethylene glycol poisoning have detectable levels of ethylene glycol in serum and urine up to 48 hours after ingestion.
  • Cystine crystals may be confused with struvite crystals. Cystine crystals are insoluble in acetic acid while struvite crystals are soluble. A urine nitroprusside test is positive for cystine.

Imaging

Crystalluria may be associated with radiographically or ultrasonographically detectable uroliths.

Diagnostic Procedures

Voiding urohydropropulsion or aspiration through a transurethral catheter to retrieve small urocystoliths.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

N/A

Precautions

N/A

Alternative Drug(s)

N/A

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Recheck urinalysis to determine if crystalluria is persistent.
  • See chapters on specific urolith types for monitoring urolithiasis.

Possible Complications

  • Persistent crystalluria may contribute to formation and growth of uroliths.
  • Crystalluria may solidify crystalline-matrix plugs, resulting in urethral obstruction.

Miscellaneous ⬆

Miscellaneous

Age-Related Factors

N/A

Abbreviation

APRT = adenine phosphoribosyl transferase

Authors Carl A. Osborne and Lisa K. Ulrich

Consulting Editor Carl A. Osborne

Suggested Reading

Albasan H, Lulich JP, Osborne CA, Lekcharoensuk C, Ulrich LK, Carpenter KA. Effects of storage time and temperature on pH, specific gravity, and crystal formation in urine samples from dogs and cats. J Am Vet Med Assoc 2003, 222(2):176–179.

Osborne CA, Davis LS, Sanna J, et al. Identification and interpretation of crystalluria in domestic animals: A light and scanning electron microscopic study. Vet Med 1990, 85:18–37.

Osborne CA, Lulich JP, Ulrich LK, et al. Feline crystalluria: Detection and interpretation. Vet Clin North Am 1996, 26369–26391.

Osborne CA, Stevens B. Urinalysis: A Clinical Guide to Compassionate Patient Care. Shawnee Mission, KS: Bayer, 1999.

Osborne CA, Lulich JP, Swanson LL, Albasan H. Drug-induced urolithiasis. Vet Clin North Am Small Anim Pract 2009, 39(1):55–63.