Types of Crystals in Urine – Causes, Factors, Identification

Crystals in urine is the condition in which solid crystalline particles are seen in urine. It is referred to as crystalluria. These crystals are formed when urine contains excess amount of minerals and waste products and they are precipitated out as solid particles.

In normal conditions, kidneys filter blood and different dissolved solutes are excreted through urine such as calcium, oxalate and uric acid. These substances are present in dissolved form. This process occurs when urine becomes supersaturated or when pH of urine is changed (acidic or alkaline) and the solutes can no longer remain dissolved then they crystallize into microscopic structures.

A small amount of crystals in urine can be a normal physiological finding. It may be influenced by diet, mild dehydration or storage of urine sample (for example refrigerated urine). In such condition, crystals does not produce any major problem and it is corrected by adequate water intake.

But large amount of crystals in urine is considered abnormal. It can act as an early indication for underlying disorders and it may increase the risk of kidney stone formation. It is also associated with urinary tract infection, inherited metabolic disorder like cystinuria and kidney toxicity due to certain drugs.

Causes of Crystals in Urine

Crystals in urine can be caused by various factors, including:

Crystals in urine is formed when dissolved substances precipitate out from the urine. It is mainly due to increased concentration of salts and alteration in urinary conditions. The causes are as follows–

1. Urine supersaturation – It is the primary cause of crystal formation. When the concentration of minerals becomes high in relation to urine volume, precipitation is occurred and crystals are formed.
2. Dehydration – It is seen when fluid intake is low. The urine becomes concentrated and solutes is more likely to crystallize.
3. Changes in urine pH – It is an important factor. Acidic urine favors uric acid crystals whereas alkaline urine favors calcium phosphate and struvite crystals formation.
4. Dietary habits – Diet rich in salt, animal proteins, purines and oxalate containing foods increases the excretion of these substances. These promotes crystalluria.
5. Cooling of urine sample – When urine is kept for long time or refrigerated, solutes may precipitate. This is referred to as in vitro crystal formation.
6. Hyperoxaluria and hypercalciuria – Increased oxalate or calcium in the body promotes calcium oxalate and calcium phosphate crystals are formed.
7. Gout – It is associated with increased uric acid production. Uric acid and sodium urate crystals is formed.
8. Diabetes and obesity – These conditions lowers the urine pH and uric acid crystals are commonly seen.
9. Liver disease – Severe liver disorders may cause leucine, tyrosine and bilirubin crystals are formed in urine.
10. Nephrotic syndrome – It is characterized by lipiduria and cholesterol crystals may be seen.
11. Cystinuria – It is a hereditary defect of renal tubular reabsorption. Excess cystine is excreted and cystine crystals are formed.
12. Primary hyperoxaluria – It is an inherited disorder where oxalic acid is overproduced in liver leading to massive calcium oxalate crystalluria.
13. APRT deficiency – It is an enzyme deficiency resulting in 2,8-dihydroxyadenine crystals formation.
14. Hereditary xanthinuria – It is a rare enzyme defect causing xanthine crystals are precipitated.
15. Urinary tract infection – Infection with urease producing bacteria increases urine pH and ammonia is produced. Struvite crystals are formed.
16. Certain drugs – High dose or prolonged use of antibiotics, antivirals or diuretics may precipitate in renal tubules and drug crystals are formed.
17. Toxins – Ethylene glycol poisoning causes rapid precipitation of calcium oxalate monohydrate crystals.
18. Radiographic contrast media – These substances may precipitate in acidic urine and mimic cholesterol crystals.

Influential Factors Affecting the Types and Abundance of Urinary Crystals

The formation of urinary crystals is influenced by different physical and chemical factors. The type of crystal formed and their abundance mainly depends upon the condition of urine. Some of the main factors are–

• Urine pH – It is the most important determinant for crystal formation. The solubility of many salts are depends on the acidity or alkalinity of urine. Uric acid and cystine crystals are formed in acidic urine. Calcium phosphate and struvite crystals are formed in alkaline urine. Change in pH alters solubility and precipitation occurs.
• Hydration status and urine volume – When there is low fluid intake the urine volume decreases. The urine becomes concentrated and supersaturation is produced. In this state dissolved substances precipitate easily and crystals is formed in increased amount.
• Dietary habits – High intake of animal protein and purine increases uric acid level in urine. This leads to formation of uric acid crystals. High sodium intake promotes calcium excretion and calcium crystals are produced. Foods rich in oxalate such as spinach, nuts and rhubarb increases calcium oxalate crystals formation. Excess vitamin C also contribute in oxalate production.
• Medications and drugs – Certain drugs are excreted through urine and may precipitate in suitable conditions. This condition is referred to as drug-induced crystalluria. Drugs like amoxicillin, acyclovir, sulfadiazine, indinavir and triamterene can form crystals especially in dehydration and at favourable urine pH.
• Bacterial infections – Urinary tract infection caused by urease producing bacteria hydrolyse urea into ammonia. This increases the alkalinity of urine. In alkaline urine struvite (magnesium ammonium phosphate) crystals are abundantly formed.
• Genetic and metabolic disorders – Some inherited metabolic disorders leads to abnormal crystal formation. In cystinuria cystine crystals are present. In primary hyperoxaluria excessive calcium oxalate crystals are formed. APRT deficiency results in 2,8-dihydroxyadenine crystals.
• Balance of promoters and inhibitors – Normal urine contains substances that inhibit crystal formation such as citrate, magnesium, pyrophosphate and Tamm-Horsfall protein. Deficiency of citrate combined with excess calcium or oxalate promotes aggregation of crystals. This imbalance increases the abundance of crystals.
• In vitro factors (Sample handling) – The storage condition of urine sample also influence crystal formation. Refrigeration decreases solubility of solutes and causes precipitation of amorphous urates or phosphates. If the sample is kept at room temperature for long time evaporation and bacterial growth may occur which alters pH and concentration leading to crystal formation.

Types of Crystals in Urine

Urine crystals are formed due to precipitation of salts in urine. These are observed during microscopic examination of urine. The formation of crystals depends upon pH, concentration of solutes and temperature. Some crystals are normally present while others indicates pathological conditions.

The types of crystals in urine are–

1. Calcium-Based Crystals

• Calcium oxalate – It is the most common type of urinary crystal. It appears in two forms– calcium oxalate dihydrate (envelope or bipyramidal shape) and calcium oxalate monohydrate (dumbbell, ovoid or picket-fence shape). These crystals are usually found in acidic to neutral urine.

• Calcium phosphate – It includes amorphous phosphate, carbapatite and brushite. They appear as granules, prisms, needles or rosettes. These are generally seen in neutral to alkaline urine.

• Calcium carbonate – These are small colorless crystals. They appear as spheres or dumbbell shaped structures. It is commonly present in alkaline urine.

2. Uric Acid and Urate Crystals

• Uric acid – It is seen in acidic urine. The shapes are diamond, rhombic, barrel or rosette form. They are yellow to brown in colour.

• Amorphous urates – These appear as yellow brown sand-like granules in acidic urine. On refrigeration it may form pink precipitate which is referred to as brick dust deposit.

• Monosodium urate – It is seen as slender needle or pencil-like prisms. These are colorless to light yellow and usually found in acidic urine.

• Ammonium biurate – These are yellow brown spherical crystals with irregular spicules. It gives a thorny apple appearance. They are commonly formed in neutral or alkaline urine.

3. Infection-Related Crystals

• Triple phosphate (Struvite) – It is composed of magnesium ammonium phosphate. These crystals resemble coffin lid shape. They are formed in alkaline urine and are associated with urinary tract infection caused by urease producing bacteria.

4. Abnormal Metabolic Crystals

• Cystine – These are colorless hexagonal plates. It is found in acidic urine and indicates cystinuria which is a genetic disorder.

• Cholesterol – It appears as clear flat rectangular plates with notched corners. It is usually seen in severe lipiduria or nephrotic syndrome.

• Bilirubin – These are bright yellow to orange brown needles or granules. It indicates increased bilirubin level commonly seen in liver disease.

• Tyrosine – It appears as fine needle like crystals.

• Leucine – It forms yellow brown spherical crystals with concentric rings. Both tyrosine and leucine are found in acidic urine and are associated with severe liver disorders.

• 2,8-dihydroxyadenine (DHA) – These are round reddish brown crystals with central spicules. It is formed due to APRT enzyme deficiency.

• Xanthine – It is rare crystal. It appears as granules or sticks and is associated with genetic enzyme deficiency or use of allopurinol.

5. Drug-Induced (Iatrogenic) Crystals

• Antibiotics and antivirals – Drugs like amoxicillin, ampicillin, acyclovir and sulfadiazine may precipitate in urine. They form needle like or broom like crystals.

• Other drugs – Indinavir forms starburst or fan shaped crystals. Triamterene forms brown spheres. Radiographic contrast media may appear as flat plates. These crystals are usually formed in renal tubules especially in dehydrated patient.

Thus, urine crystals are important diagnostic indicators. Identification of these crystals is essential for diagnosis of metabolic disorders, infections and renal diseases.

FAQ

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