Hyperoxaluria

Hyperoxaluria occurs when there is too much oxalate in the urine, leading to kidney stones and potentially serious kidney damage that can affect long-term health.

Table of contents

• What is hyperoxaluria?
• Types of hyperoxaluria
• What causes hyperoxaluria?
• Signs and symptoms
• When does hyperoxaluria start?
• How is hyperoxaluria diagnosed?
• Treatment approaches
• Living with hyperoxaluria

What is hyperoxaluria?

Hyperoxaluria is a condition that happens when there is too much oxalate (a natural chemical the body makes) in your urine^[1]. Oxalate is also found in some foods. Your kidneys normally filter oxalate, and it leaves your body through urine or stool^[9].

In people with hyperoxaluria, oxalate builds up in the kidneys and combines with calcium to form calcium oxalate crystals and kidney stones. These crystals can damage the kidneys and cause them to stop working properly over time^[9]. The normal upper level of urinary oxalate is 40 mg in 24 hours. Men have a slightly higher normal value than women, mainly due to larger body size and meal portions^[5].

Even small changes in urinary oxalate levels can have a very significant impact on kidney stone formation^[2]. When the kidneys fail to work properly and the glomerular filtration rate (the measure of how well kidneys filter blood) drops below 30 to 45 mL/min, oxalate begins to collect in the blood. This leads to a condition called oxalosis, where calcium oxalate crystals deposit in other organs such as the heart, bones, blood vessels, eyes, and skin, causing serious multi-organ disease^[4].

Types of hyperoxaluria

There are three main types of hyperoxaluria: primary, enteric, and dietary^[5].

Primary hyperoxaluria (PH) is a rare genetic disorder that runs in families. It occurs when the liver either does not produce enough enzymes to prevent oxalate overproduction, or the enzymes do not work properly^[9]. There are three subtypes of primary hyperoxaluria, all involving genetic mutations that affect the liver. Primary hyperoxaluria type 1 (PH1) is the most common and has the worst outlook. About 73% to 100% of PH1 patients develop kidney stones^[4].

Enteric hyperoxaluria happens when a digestive system condition causes the body to absorb too much oxalate, leading to excess oxalate in urine. This can occur with conditions like Crohn’s disease and inflammatory bowel disease, or after gastric bypass surgery when the small intestine cannot absorb nutrients properly^[9].

Dietary hyperoxaluria occurs when you eat too many foods high in oxalate. Examples include spinach, beets, soy, almonds, and potatoes^[9].

What causes hyperoxaluria?

Hyperoxaluria develops when too much of a chemical called oxalate builds up in the urine. The causes vary depending on the type^[7].

In primary hyperoxaluria, changes in genes that are passed down in families cause the liver to make too much oxalate. The body gets rid of excess oxalate through the kidneys in urine. The extra oxalate can combine with calcium in the kidneys to form stones and damage kidney tissue^[7].

Oxalate is naturally made by plants, mainly in their leaves, nuts, fruits, and bark. The amount of oxalate in plants depends on the specific variety and the soil and water conditions where they grow. Plants grown in fields with high calcium in the groundwater tend to have higher oxalate levels^[5]. This is why calculating dietary oxalate precisely is difficult—oxalate content within the same plant type can vary widely. For example, potatoes contain 5.5 to 30 mg of oxalate per 100 g, while wheat bran has 58 to 524 mg per 100 g^[5].

Most oxalate in the body comes from the liver as part of normal metabolism. Oxalate is absorbed primarily from the colon but can be absorbed anywhere in the intestinal tract^[5].

Signs and symptoms

Often, the first sign of hyperoxaluria is a kidney stone. Kidney stones that form in children and teenagers are likely caused by a health problem like hyperoxaluria. All young people with kidney stones should have a checkup that includes a test measuring oxalate in the urine. Adults who keep getting kidney stones should also be tested^[1].

Kidney stone symptoms can include^[1]:

• Sharp pain in the back, side, lower stomach area, or groin
• Urine that looks pink, red, or brown due to blood
• Frequent urge to urinate
• Pain when urinating
• Not being able to urinate or urinating only a small amount
• Chills, fever, upset stomach, or vomiting

Not everyone with hyperoxaluria has kidney stones. Other signs of hyperoxaluria can include blood in the urine, recurring urinary tract infections, and in infants, failure to thrive^[9].

In primary hyperoxaluria, kidney stones typically appear light whitish or pale yellow with loose aggregations of different-sized crystals, averaging about 1.6 cm in size (ranging from 0.5 to 4.5 cm)^[4].

When does hyperoxaluria start?

Symptoms of hyperoxaluria can develop anytime from infancy to adulthood. The average age that symptoms appear is 5 years old^[9].

People with primary hyperoxaluria tend to get recurring kidney stones as a child or teenager, usually before age 20. If infants develop primary hyperoxaluria, the condition tends to be severe. About 50% of these children will experience kidney failure by age 15, and about 80% will experience kidney failure by age 30^[9].

People with enteric and dietary hyperoxaluria tend to develop kidney stones and other symptoms in adulthood^[9].

How is hyperoxaluria diagnosed?

Diagnosis begins with a thorough physical exam and questions about your health history and eating habits^[10].

Tests to diagnose hyperoxaluria may include^[10]:

• Urine tests to measure oxalate and other substances. You are given a special container to collect your urine over 24 hours, which is then sent to a lab
• Blood tests to check how well your kidneys work and measure oxalate levels in the blood
• Stone analysis to find out what kidney stones are made of after you pass them through urine or have them removed with surgery
• Kidney X-ray, ultrasound, or CT scan to check for any kidney stones or calcium oxalate buildup in the body

Additional tests may be needed to confirm hyperoxaluria and see how the disease has affected other parts of the body. These can include DNA testing to look for gene changes that cause primary hyperoxaluria, kidney biopsy to check for oxalate buildup, echocardiogram to check the heart, eye exam to check for oxalate deposits in the eyes, and bone marrow biopsy to check bones^[10].

If you learn you have primary hyperoxaluria, your siblings are also at risk and should have tests. If your child has primary hyperoxaluria, genetic testing and counseling can help guide decisions about having more children^[10].

Treatment approaches

Treatment depends on the underlying cause and severity of hyperoxaluria. Many treatments can be combined for increased effectiveness^[5].

Staying hydrated is crucial for all types of hyperoxaluria. Drinking lots of fluids helps flush out the kidneys so oxalates do not build up and turn into stones. Adults and older teenagers should aim to drink at least 4 liters of water daily; school-age children need 2 to 3 liters; and infants and small children need 1 to 1.5 liters. Some people, especially children, may need a feeding tube to ensure adequate fluid intake^[13].

Dietary changes can help manage hyperoxaluria. While people with primary hyperoxaluria have high oxalate due to a genetic defect rather than diet, limiting oxalate-rich foods can prevent even higher levels. Foods high in oxalates include chocolate, cocoa, rhubarb, leafy greens like spinach, black tea, nuts, peanut butter, and star fruit^[17]. Vitamin C supplements should be avoided, as vitamin C gets turned into oxalate in the body^[17].

Eating more calcium-rich foods may help lower oxalate levels in the body, as calcium binds to oxalate so it leaves the body in stool rather than urine. Limiting sodium to no more than 1,500 milligrams daily also helps, as sodium raises calcium levels in urine^[17].

For primary hyperoxaluria type 1, some patients may respond to pyridoxine (vitamin B6), though about two-thirds do not. A trial is recommended, and treatment should be discontinued if there is no response^[13].

Alkali citrate therapy (either as lemon juice or supplements) can help prevent future stones by binding to calcium in urine and preventing it from binding to oxalate^[17].

For kidney stone removal, procedures like percutaneous nephrolithotomy or ureteroscopy are recommended. Extracorporeal shock wave lithotripsy is not recommended as it can contribute to kidney injury in PH patients^[13].

Patients with severe kidney disease may need dialysis—often as frequently as 6 days per week—though dialysis cannot remove all the oxalate the body produces^[13]. In some cases, particularly for primary hyperoxaluria type 1 with chronic kidney disease stage 3b, simultaneous liver-kidney transplant may be recommended. About 34% to 46% of PH1 patients may require organ transplant^[13].

Two new therapies based on RNA interference have been approved for primary hyperoxaluria type 1. These work by reducing liver enzymes involved in oxalate overproduction^[13].

Living with hyperoxaluria

Managing hyperoxaluria can be challenging, from multiple medications to drinking substantial amounts of water to frequent medical appointments. Staying motivated to follow your management plan is important for protecting kidney health^[18].

Tips for staying hydrated include setting phone reminders to drink water, bringing water everywhere, using apps to track intake, keeping filled water bottles handy, eating high-water-content foods like fruits and vegetables, and setting drinking deadlines throughout the day^[18].

Building a strong care team is essential. Your team may include a nephrologist who specializes in kidney disease, a urologist for stone removal, a registered dietitian for nutrition guidance, dialysis nurses if needed, social workers for emotional support, and financial counselors^[16].

People with chronic kidney disease often experience anxiety and depression. If you feel overwhelmed, speak to your healthcare team and consider working with a mental health professional. Relaxation techniques like meditation and breathing exercises, regular exercise, journaling, and staying connected with friends can help manage stress^[18].

Connecting with others who have hyperoxaluria through patient organizations can provide valuable support. The Oxalosis and Hyperoxaluria Foundation offers educational resources, patient registries, and opportunities to connect with other families facing similar challenges^[16].

• Kidneys
• Liver
• Urinary tract
• Intestines