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Hypocitraturia - Causes, Symptoms, Diagnosis, and Treatment

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Hypocitraturia is a metabolic disorder with a low level of citrate excreted in the urine, less than 320 mg/day. Check out the article to learn more.

Medically reviewed by

Dr. Manzoor Ahmad Parry

Published At September 21, 2022
Reviewed AtMay 2, 2023

What Is Hypocitraturia?

Hypocitraturia is commonly seen in patients with nephrolithiasis, metabolic acidosis, and chronic diarrhea. However, hypocitraturia itself may not be associated with significant death or illness. Increasing proximal renal tubular reabsorption by hypocitraturia reduces urinary citrate levels. Urine citrate levels below 320 mg/day are generally low, but citrate excretion may be less than 100 mg/day in severe cases. Low urine citrate levels are a dangerous factor in kidney formation because citrate inhibits calcium formation.

What Causes Hypocitraturia?

Hypocitraturia is usually idiopathic (unknown) but may be caused by distal renal tubular acidosis (RTA), hypokalemia, intestinal dysfunction, and a high-protein, low-alkaline diet. Genetic, pharmacological, and other viral diseases also play a role.

The following are the different causes of hypocitraturia:

  • Acid-base imbalances (an abnormality in the human body's normal acid-base balance that causes the plasma pH to deviate from the normal range).

  • Distal (type 1) renal tubular acidosis (a defect in the kidney tubes that causes acid to build up in the blood).

  • Diarrhea or malabsorption (difficulty in the digestion or absorption of nutrients from food).

  • Hypokalemia (low potassium level).

  • A diet high in animal protein.

  • High sodium diets.

  • A diet with fewer fruits or vegetables.

Medications:

  • Thiazide diuretic.

  • Amiloride.

  • Acetazolamide treatment.

  • ACE inhibitors.

  • Calcitonin,calcium and vitamin D supplements.

  • Ethacrynic acid.

  • Topiramate.

  • VDR polymorphisms.

  • NaDC-1 gene polymorphisms.

Other Related Disorders

  • Kidney dysfunction (chronic kidney disease that leads to renal failure).

  • Hyperaldosteronism (a condition in which one or both adrenal glands produce an abnormally large amount of the hormone aldosterone).

  • Glycogen retention syndrome (a rare condition in which the body changes the way it uses and stores glycogen, a type of sugar or glucose).

  • Hypocalciuria (Atypically low calcium concentration in the urine)

  • Hypomagnesemia (low level of magnesium).

What Are the Symptoms of Hypocitraturia?

Hypocitraturia is usually undetectable until the kidney stones move between the kidneys or pass into the ureter and cause pain or discomfort. If stones enter the ureter, it may block urine flow and cause the kidneys to swell and the ureter to become spasm, which can be very painful. At that point, the patient may have the following symptoms:

  • Severe pain in the side and back, under the ribs.

  • Pain resulting in lower abdomen and groin.

  • Pain that comes with waves and fluctuates with intensity.

  • Pain or burning sensation while urinating.

Other Signs and Symptoms May Include:

  • Urine in pink, red, or brown color.

  • Flaky or smelly urine.

  • The continued need for urination, more than usual, or urination in small amounts.

  • Nausea and vomiting.

  • Fever and cold, if there is an infection.

What Are the Risk Factors for Hypocitraturia?

Risk factors for hypocitraturia are as follows:

  • Eating more meat increases the urine excretion of calcium, oxalate, and uric acid and reduces the pH of urine and citric excretion.

  • Consumption of high protein, low-carbohydrate foods in weight loss has led to concerns about an increased risk of stone formation. In addition, these diets are associated with decreased urinary citrate and pH levels and increased calcium and sodium levels in the urine.

  • Excess sodium can also cause hypocitraturia, which leads to an increase in stone formation.

  • Hypercalciuria can be caused by administering Corticosteroids, Antacids containing aluminum, Loop diuretics, and vitamin D.

  • Genetic factors also play an essential role.

What Are the Diagnostic Tests for Hypocitraturia?

The diagnostic tests for hypocitraturia are,

  1. Blood Test: A blood test may reveal too much calcium or uric acid in the blood. The results of a blood test help monitor kidney health and may lead the doctor to evaluate other medical conditions.

  2. Urine Testing: A 24-hour urine collection test may show that the patient is excreting a lot of minerals that form stones or a few stone blocks. In this test, the doctor may ask to make two sets of urine for two consecutive days.

  3. Imaging Tests: Tests are performed to know the location of kidney stones.

  • Computerized tomography (CT) may reveal even tiny stones.

  • A simple abdominal X-ray is used less frequently because this type of imaging can miss detecting small kidney stones.

  • Ultrasound, a rare and easy-to-perform test, is another image option for diagnosing kidney stones.

  1. Analyzing the Passed-Out Kidney Stones: The patient may be asked to urinate with a filter to catch passing stones. Analysis of the lab will reveal the shape of the kidneys. The doctor uses this information to determine the cause of kidney stones and plan to prevent the formation of multiple kidney stones.

How to Treat and Manage the Problem of Hypocitraturia?

Treatment of low urinary citrate is aimed when the underlying cause is known; treatment includes improving the diet and setting up drugs that inhibit carbonic anhydrase. If this is not possible, or the cause is idiopathic (unknown), treatment is primarily with oral alkalinizing urine medications.

Treatment for Severe Hypocitraturia:

  • Severe Hypocitraturia: When excretion isless than 100 mg /day, it is treated according to the underlying cause.

  • Chronic Diarrheal State: Potassium citrate, 20 to 40 mEq, two to four times daily as needed to optimize urinary citrate excretion.

  • Infection Stones: Potassium citrate, antibiotics, stone removal concerning struvite stones (infection), and potassium citrate should be used with caution in these cases, as alkalinization will increase the formation of these stones.

  • Mild and Moderate Hypocitraturia: The recommended therapy for mild to moderate hypocitraturia is the administration of supplemental potassium citrate and dietary restriction of animal protein. The dose is adjusted based on monitoring and evaluating urinary pH and citrate levels obtained at two to three months of treatment.

When the condition is stable, repeated tests can be performed every four to six months and then, annually, if stable. Performing a complete 24-hour metabolic test of urine, including serum potassium and urine volume, calcium, uric acid, oxalate, phosphate, sodium, and magnesium, in addition to citrate, is essential.

Dietary Considerations:

  • Intake of Plenty of Fluids - Enough to produce 2 L or more urine per day.

  • Sodium Restriction - Avoid the use of processed or salty foods, with a daily sodium intake of 2400 mg.

  • Oxalate Inhibition - Patients should avoid nuts, whole grains, black roughage, chocolate, tea, and vitamin C supplements

  • Animal Protein Restriction - Limit the intake of meat products.

Conclusion:

Hypocitraturia is characterized by a low citrate level in the urine. A urine citrate level of less than 320 mg/day is considered low, but in severe cases, citrate excretion can be as low as 100 mg/day. Low urine citrate levels are a risk factor for kidney stone formation. Gout, urinary tract infection, certain medications, high animal protein consumption, and distal renal tubular acidosis are some of the causes of low urine citrate and calcium kidney stone formation.

Dietary changes and the administration of citrate preparations or other alkali therapy can help correct hypocitraturia. Early diagnosis and active management are of great help in reducing the chances of developing kidney disease.

Frequently Asked Questions

1.

Can Hypocitraturia Cause Kidney Stones?

Hypocitraturia is a metabolic disorder marked by a low level of citrate excretion in the urine—less than 320 mg per day. Low urinary citrate excretion is known to increase the risk of developing kidney stones. Patients with metabolic acidosis (condition with lower pH levels), chronic diarrhea (loose stools for at least four days a week), and nephrolithiasis (kidney stones) frequently exhibit hypocitraturia (less of urine citrate).

2.

How Is Hypocitraturia Diagnosed?

To diagnose kidney stones, medical professionals may use lab or imaging tests.
- Lab Test: A urine test can reveal whether the urine has high concentrations of minerals that can cause kidney stones. A health care provider can also identify the type of kidney stone using urine and blood tests.
- Imaging Tests: To detect kidney stones, medical professionals use imaging tests. The tests may also reveal issues, such as a blockage in the urinary tract or a congenital disability, that led to the formation of a kidney stone.

3.

What Is the Treatment for Low Urine Citrate?

Treatment options include altering the diet and prescribing carbonic anhydrase inhibitors. If this is not possible or the cause is idiopathic (unknown), oral alkalinizing urine medications are the mainstay of treatment. Repeated tests can be done every four to six months if the condition is stable and then once a year if the condition is stable.

4.

What Is a Normal Level of Citrate in the Urine?

24-hour urinary citrate normal is close to 320 mg. For people with calcium stones, the optimal 24-hour urinary citrate concentration is around 320 mg per 1,000 ml of urine, usually resulting in a total of about 640 mg or more and assuming an ideal daily 2,000 ml of urine.

5.

What Do Elevated Levels of Citrate Indicate?

Citrate levels above a certain point can signify ammonia toxicity. Elevated urinary citrate could be a sign of metabolic acidosis, brought on by damaged proximal tubular function in the kidney, which causes citrate to be wasted in the urine. Pancreatic dysfunction is another potential reason for elevated urine citrate because it would result in less bicarbonate production and less citric acid utilization.

6.

What Are the Foods That Contain Citrate?

Citrate, or citric acid, is a naturally occurring antioxidant known to prevent calcium-based stones from forming. Citrus fruits, which are high in natural citric acid, include the following:
- Lemons.
- Limes.
- Oranges.
- Grapefruits.
- Berries

7.

What Is the Role of Citrate in the Body?

Citrate connects many crucial cellular functions, including protein modification, carbohydrate, and fatty acid metabolism. However, the most striking aspect of its control over immune cell function may be its ability to produce acetyl-CoA for the acetylation of histones. In addition, citrate prevents the growth and agglomeration of crystals by complexing with calcium in the urine, preventing spontaneous nucleation and inhibiting spontaneous growth.

8.

What Are the Effects of Citrate?

Side effects of citrate include:
- Diarrhea.
- Nausea.
- Muscle spasms.
- Metabolic alkalosis.
- Vomiting.
- Stomach pain.
- Fluid retention.
Dr. Manzoor Ahmad Parry
Dr. Manzoor Ahmad Parry

Nephrology

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