Calcium Oxalate Crystals · What Are They, Causes, Signs and Symptoms, and More

Calcium oxalate crystals are a common component of kidney stones, forming when a positively charged calcium ion binds to a negatively charged oxalate ion, resulting in a black, yellow, or dark brown stone that is shaped like an envelope or a dumbbell under microscopy. Sometimes, instead of oxalate, calcium binds to negatively charged phosphate groups to form calcium phosphate stones. These two types of stones account for approximately 80% of kidney stones globally.  

Calcium oxalate stones are the most common type of kidney stones, followed by calcium phosphate, struvite, and uric acid stones. Stone formation occurs when there is an excess of crystal-forming substances that can’t be dissolved in the urine. High urinary excretion of certain substances—such as calcium, oxalate, uric acid, and cysteine—can promote stone formation. On the other hand, increased excretion of other substances, such as citrate, has a protective effect. Disturbances in urinary pH, a low urine volume, and a lack of protective substances that prevent the crystals from sticking together may also contribute to stone formation. 

The main risk factor for developing calcium oxalate crystals is increased excretion of calcium and oxalate in the urine. These abnormalities can be idiopathic, which means their cause is unknown, or can arise due to systemic diseases, such as hyperparathyroidism, renal tubular acidosis, and fat malabsorption. The relative concentrations of ions, like calcium and oxalate, increase in states of low urine volume, such as with dehydration, contributing to stone formation.  

With hyperparathyroidism, overproduction of parathyroid hormone (PTH) causes high serum calcium levels, which forces the kidneys to excrete more calcium in the urine. In renal tubular acidosis, the kidneys cannot acidify the urine, leading to a persistently alkaline, or basic, urine. Over time, this defect results in chronic metabolic acidosis. To buffer the acid in the blood, calcium is released from bones, which increases calcium levels in the blood and its excretion in the urine. While calcium oxalate stones are more likely to form in acidic urine, they can still form in alkaline urine, especially in the presence of excess calcium.  

Fat malabsorption can occur in Crohn disease or in individuals who have had gastric bypass surgery. When fat cannot be absorbed in the intestine, it binds to calcium leaving many oxalates free to be absorbed in the intestine. This contributes to higher oxalate levels in the blood which can promote the formation of calcium oxalate stones. 

On the other hand, citrate can protect against stone formation by forming complexes with calcium and inhibiting further aggregation and growth of crystals. For this reason, a low excretion of citrate, called hypocitraturia, is associated with an increased risk of developing stones. In most cases, the cause of hypocitraturia is not known, however, it has been associated with the presence of acid-balance disturbances, low levels of potassium in the blood, high-protein diets, and chronic diarrhea.   

Signs and symptoms of calcium oxalate crystals depend on their size, shape, and location on the urinary tract. Most calcium oxalate stones form in the renal pelvis, where they usually cause no pain or obstruction of the urine flow.  

Eventually, stones might move from the kidney into the ureter, which is a narrow tube that connects the kidneys to the bladder. The passage of the ureteral stone causes increased pressure within the ureter, followed by spasms of the smooth muscle lining and distension of the walls. This typically presents as a renal colic, with severe flank pain of sudden onset that can radiate to the back, inner thigh, or groin. Due to the intense pain, individuals may find themselves feeling restless or unable to find a comfortable position. Some individuals may even experience sweating or nausea and vomiting as a physiological response to the intense pain. In addition, as the stone moves down the ureter, it can cause damage resulting in blood in the urine. When stones reach the bladder, they can further irritate and obstruct the bladder, leading to frequent or painful urination.  

Ultimately, small stones may spontaneously be eliminated through urine, relieving the pain. If the obstruction isn’t resolved, it can lead to severe complications, including chronic bladder discomfort and a decrease in renal function and hydronephrosis due to urine build-up. Additionally, the obstructed kidney can become infected, causing obstructive pyelonephritis, a life-threatening condition that requires urgent surgery to drain the kidney, as well as intravenous antibiotics. 

Asymptomatic calcium oxalate crystals may be detected incidentally with imaging. While most calcium stones are visible on an abdominal X-ray, a non-contrast CT scan may be ordered to detect the exact location and size of the stone, as well as determine its composition by looking at its density. Alternatively, especially for pregnant individuals, an ultrasound can be used to detect the location as a hypoechoic density.  

Once the acute episode has subsided, a metabolic evaluation may be performed to assess the stone type in order to find the best way to prevent recurrence. The exact composition of the stone can be determined by analyzing the stone crystals in the urine, which can be collected with a urine strainer if the stones pass spontaneously or at the time of stone extraction procedures. In cases where stone composition is unknown, assessing the characteristics of a 24-hour urine sample may be the only tool available to guide therapy. 

Treatment of calcium oxalate crystals consists of two steps. The first step is to treat the pain associated with the passage of kidney stones. This may include non-steroidal anti-inflammatory drugs (NSAIDs) to reduce the inflammation and ureteral spasms, intravenous fluids, and medications such as ondansetron to help with nausea and vomiting. Analgesia with an opioid may also be considered for severe pain. 

Subsequent treatment depends on the location and size of the stone, as well as the presence of complications. Small stones (i.e., <5-7 mm) have around a 50 to 60% chance of passing spontaneously, so expectant management is appropriate. Some cases may be treated with medical expulsive therapy, in which medication such as tamsulosin is given to relax the ureteral smooth muscle and help the stone pass more easily. Larger stones may require urology consultation for extraction procedures, such as lithotripsy or endoscopic removal.  

Lithotripsy, also known as extracorporeal shock wave lithotripsy (ESWL), is a non-invasive procedure that uses ultrasonic shock waves to fragment the stone, breaking it into smaller pieces that can be excreted in the urine. ESWL is generally effective for stones made of calcium oxalate dihydrate, which is more brittle and easier to break. However, calcium oxalate monohydrate stones are harder and may not fragment as well with lithotripsy, thereby needing multiple sessions or alternative treatments. 

When lithotripsy isn’t possible, surgical removal of the stones is the preferred treatment. Stones can be removed either by ureteral endoscopy or through minimally invasive surgery, as in percutaneous nephrolithotomy (PCNL). PCNL may be necessary for large stones (> 2 cm) or those that can’t be removed endoscopically because of their shape. 

Many individuals that develop calcium oxalate stones are at risk for future recurrence. Because of that, increased fluid intake and a diet that is low in sodium, oxalate, and non-dairy animal protein are recommended to prevent calcium stone formation.    

Specifically, individuals may be recommended to limit the amount of animal proteins and other oxalate-rich foods, such as spinach, rhubarb, beets, nuts, chocolate, and tea. Contrary to what might be expected, dietary calcium, such as from dairy products, can bind to oxalates in the gut and prevent their absorption into the bloodstream, thus reducing their excretion in the urine. For this reason, ensuring a minimum intake of 1,000-1,200 mg of calcium from the diet is recommended. Finally, vitamin C is metabolized into oxalate, so high doses, those over 1,000 mg daily, should be avoided in individuals prone to oxalate stones. 

Preventive treatment may also include thiazide diuretics, which increase both diuresis and calcium reabsorption by the kidneys. Potassium citrate may also be prescribed due to its ability to raise urinary pH and increase citrate levels, which prevents stone formation by inhibiting crystal growth and aggregation.