What is Hypocitraturia and Renal Calculi?
Citrate, which naturally prevents the formation of stones, works by combining with calcium in the urine. This prevents the calcium from forming crystals which can clump together and form stones. If a person’s citrate levels are too low, there’s a higher chance of calcium stones forming, which can lead to the development of kidney stones.
This condition, known as hypocitraturia, is defined by low or insufficient citrate in the urine. It’s one of the most common and manageable causes of kidney stones. This issue is a notable metabolic disorder that contributes to the development of kidney stones. Importantly, it’s believed that half of all symptomatic kidney stones could be avoided with the correct diagnosis and preventative treatment for chemical conditions that increase the risk of developing kidney stones.
Unfortunately, preventive medical evaluation and treatment for kidney stone disease are not used as much as they should be, and the approach can be inconsistent and generally inadequate. Moreover, people with kidney stones, even those without symptoms, often experience a significantly poorer quality of life.
The cost of treating kidney stones, both direct and indirect, is estimated at over $10 billion every year, and it’s expected to go over $15 billion by 2030. This increase is due to a higher rate of stone disease from related conditions like diabetes and obesity, an increase in population, and the impact of global warming.
Hypocitraturia was first reported in 1934 and later confirmed in 1941. However, this information was initially disregarded or attributed to bacterial consumption of citrate. It wasn’t until 1962 that it was first suggested that hypocitraturia was a unique urinary chemical disorder in patients with kidney stones.
Hypocitraturia is officially defined as a urinary citrate excretion of less than 320 mg per day, but many experts have questioned this definition. It’s estimated to be present in about 30% (ranging from 10% to 60%) of all individuals who form kidney stones. In fact, it is the only identifiable stone-promoting chemical abnormality in about 10% of all individuals who form calcium stones. It’s also often associated with other metabolic issues in about half of these people. Long-term usage of potassium citrate supplements can decrease the likelihood of developing calcium kidney stones by 80%. This supplement has shown to reduce the recurrence of kidney stones in patients who stick to the treatment.
What Causes Hypocitraturia and Renal Calculi?
In normal individuals, the amount of citrate in urine is directly related to the net amount of alkali absorbed from our diet. Having a low level of citrate in the urine can sometimes be associated with unhealthy dietary choices, such as eating a lot of meat and salt, but not enough fruit (especially citrus). Certain medications such as thiazides, ACE inhibitors, topiramate, and acetazolamide can decrease the citrate levels in the urine. Furthermore, conditions like irritable bowel syndrome (IBS), colitis, short bowel syndrome, chronic diarrhea, and having gone through a specific type of weight loss surgery (Roux-en-Y gastric bypass surgery) can also lead to low urinary citrate levels.
Urinary citrate levels are usually higher in females and in conditions such as metabolic alkalosis and due to substances like estrogens, parathyroid hormone, growth hormone, and vitamin D. Testosterone in males, anorexia, and different forms of acidosis (a condition where there’s too much acid in body fluids) can decrease these levels. Although a person’s ethnic background doesn’t significantly affect urinary citrate excretion, your genetic makeup can play an important role in these levels.
Specific causes of decreased citrate levels in urine (hypocitraturia) include:
– Acetazolamide therapy: This creates an excess of chloride acid in the blood by reducing bicarbonate reabsorption in the kidneys.
– ACE inhibitors: This is a type of medicine used to treat high blood pressure and heart failure.
– Autosomal dominant polycystic kidney disease: This is an inherited condition that causes small, fluid-filled sacs called cysts to develop in the kidneys.
Certain conditions such as chronic diarrhea syndrome, colitis, and IBS lead to a loss of alkali in the stool, which can also cause a burn-like sensation in the rectum. In chronic renal failure, a reduced rate of filtering by the kidneys results in less filtered citrate. This effect is offset by increased citrate excretion, so low citrate levels in the urine is typically not apparent until kidney failure is relatively advanced.
Some patients may demonstrate a reduced response to oral citrate supplementation due to a primary intestinal defect. Dietary factors involved usually include a high-animal protein diet, high sodium intake, low citrus, and low alkali intake.
Conditions like chronic diarrhea, colitis, and IBS can significantly increase the overall risk of nephrolithiasis (kidney stones) by up to 38% compared to the general population. Chronic diarrhea causes significant bicarbonate loss, leading to low citrate levels in the urine. Inflammatory changes in the bowel wall, surgical resections, and intestinal malabsorption also contribute to citrate loss and low citrate levels in the urine.
Among different metabolic acidotic conditions due to kidney disorders, what we call distal renal tubular acidosis is consistently associated with kidney stones, usually leading to the formation of calcium phosphate stones. This condition arises from a failure of hydrogen ion excretion in the kidneys, leading to metabolic acidosis. This acidosis is partially balanced by calcium released from bone, contributing to osteoporosis. Moreover, increased absorption of calcium in the intestine and reduced reabsorption of calcium in the kidneys result in too much calcium in the urine.
Gastric bypass surgery may also cause a reduction in citrate levels in the urine. Although this type of surgery is no longer the most commonly performed weight-loss procedure in the United States, it still constitutes a significant portion of all weight-loss surgeries. Patients who have undergone this surgery typically experience a 40% reduction in urinary citrate alongside a 50% or more increase in urinary oxalate and a 30% decrease in daily urinary volume. These combined changes significantly increase their risk for kidney stones.
Topiramate therapy, which is used for the treatment of seizures, migraines and sometimes for weight loss and pain management, also leads to a significant reduction in urinary citrate levels. It induces a mild metabolic acidosis condition leading to low citrate levels in the urine, along with other unwanted chemical effects. For patients with kidney stones taking topiramate and exhibiting low citrate levels in their urine, potassium citrate therapy can help increase the citrate levels and reverse other unwanted chemical effects.
Risk Factors and Frequency for Hypocitraturia and Renal Calculi
Hypocitraturia, or having low levels of citrate in the urine, is seen with varying frequency. Its occurrence seems to be increasing, particularly in overweight individuals or people taking a medication called topiramate. No significant difference has been found in rates of hypocitraturia among different ethnic backgrounds, including Whites, Blacks or Asians, even though kidney stones are more commonly reported in Caucasians. Also, elderly patients with kidney stones are more likely to have hypocitraturia than younger patients.
Women generally have higher citrate levels than men; however, among those who form stones, women have a higher likelihood of hypocitraturia compared to men. In females who form stones, hypocitraturia is more common in those before menopause than those after. The peak urinary citrate levels in premenopausal women align with when their estrogen, a hormone, is at its highest during their menstrual cycle.
More and more women are being diagnosed with kidney stones. The reasons for this are not completely understood but may be due to changes in activity levels, diet, and stress as a result of more women working. Also, women are more likely to have higher obesity rates, diet more often, and get weight loss surgery—all factors contributing to a higher risk of forming kidney stones. Furthermore, women are more at risk of developing kidney stones after pregnancy. For example, women under the age of 50 have an almost 100% increased risk of developing kidney stones after a single pregnancy, with the risk increasing with each additional pregnancy.
Signs and Symptoms of Hypocitraturia and Renal Calculi
Hypocitraturia, a condition where the urine has lower than normal levels of citrate, does not have any characteristic physical signs or a specific medical history. However, patients who are on certain medications like acetazolamide or topiramate, or those who have had kidney stones or nephrocalcinosis (a condition where calcium salts accumulate in the kidneys), are at a greater risk. People who have had kidney stones made up of pure uric acid might still require treatment to make their urine more alkaline, even though their citrate levels might be normal. For more details, please check out StatPearls’ guide on “Uric Acid Nephrolithiasis”.
There are also other risk factors that might increase a person’s chances of developing hypocitraturia. They include:
- Having undergone a gastric bypass surgery, particularly the Roux-en-Y type
- Conditions like irritable bowel syndrome (IBS) or chronic diarrhea
- Past intestinal surgeries
- Having gout
- A personal or family history of kidney stones (nephrolithiasis)
- Previous surgeries for kidney stones
Reviewing past urine tests over a 24-hour period can be beneficial in preventing the formation of kidney stones. Checking the chemical makeup of previously removed kidney stones can also be insightful.
Testing for Hypocitraturia and Renal Calculi
To diagnose something called hypocitraturia, a health condition where there’s a low level of citrate in the urine, a 24-hour urine test is typically needed. If the first test’s results come back normal, some doctors recommend a second test to ensure the first results weren’t affected by changes in your everyday lifestyle. For example, differences in diet, exercise, the amount of water you drink, or even daily routine can impact your urine.
Some medical clinics might even ask for a second 24-hour urine test three months after starting treatment, just to double-check the results and make any necessary changes to the treatment plan. It’s also possible for certain patients to have hypocitraturia without needing a test. For example, patients with a history of gastric bypass surgery, irritable bowel syndrome (IBS) with chronic diarrhea, or those who are taking specific medications could potentially have hypocitraturia.
There’s some debate about when the best time is to do these tests, but they should always be done as an outpatient procedure rather than in the hospital. Hospitals could control and modify your diet and fluid intake too much for accurate results. It’s best for patients to go back to their normal diets and routine after leaving the hospital for optimal results. Some experts also suggest waiting at least 30 days after a kidney stone incident or surgery before performing the test.
The official definition of hypocitraturia currently used by many laboratories has been questioned by several experts. This definition, which is based on having less than 320 mg of citrate per 24 hours in your urine, was established through statistics and doesn’t take into account other factors like age, gender, body mass, or the type of kidney stone. Understanding what is considered “normal” in these tests can be challenging because labs only provide standard ranges and not optimal or target levels.
Some patients may have normal or high citrate levels in their urine, but would still benefit from a treatment called alkalinization therapy because they have acidic urine. This is particularly common in patients who form kidney stones because of the acid in their urine. To target this group, other measurement methods such as the citrate-to-creatinine ratio or the calcium-to-citrate ratio can be used, but a 24-hour urine test is the gold standard.
Although the official standard is having 320 mg or more of citrate concentrations per liter of urine in a 24-hour period, it’s recommended to consider treatment if the concentration is less than 250 mg/L. The optimal level would be 640 mg or more. Ratios such as less than 180 mg citrate per gram of creatinine or over 0.33 mg calcium per mg citrate in random urine testing should also be considered for treatment.
As far as optimal ranges for urine pH, for most people who form kidney stones, it’s ideal to have a pH between 6 and 6.5. For people who form uric acid stones, 6.5 is ideal for maintenance and 7 for dissolution. Those with cystinuria should aim for a pH of 7.5.
Treatment Options for Hypocitraturia and Renal Calculi
If your doctor tells you that you exhibit low levels of citrate in your urine, they may recommend several treatment strategies. These might aim to address the underlying cause, such as adjusting your diet or stopping medications that lower citrate levels. If the cause can’t be determined or the treatment is unsuccessful, you may be prescribed medications to increase the pH (or reduce the acidity) of your urine.
Diet changes, especially adding foods high in citrate, can sometimes improve your citrate levels. However, you may need to consume these foods in large amounts for a noticeable change. Citrus fruits like lemons and oranges are high in citrate and can be consumed as juice. Another option is coconut water, which although not very high in citrate, can significantly increase urinary citrate levels due to its high alkaline content. It is important to note that some juices, like orange juice, are high in sugar and may not be as effective as medications. Although not thoroughly tested, calcium citrate is also sometimes recommended as it boosts urinary citrate levels without significantly affecting stone production.
In cases where dietary changes aren’t enough, doctors often recommend potassium citrate supplements. These are helpful because they balance out calcium levels in the body and prevent the formation of calcium oxalate, a common substance found in kidney stones. As with any supplement, it’s important to frequently monitor the levels of potassium in your blood, especially if you also consume other potassium supplements or have kidney problems.
Potassium citrate supplements come in tablet form and are generally tolerated well by patients. They are also relatively inexpensive and effective. However, it’s important to take these supplements regularly and as directed for the best results. They work by increasing the amount of calcium bound in the gut, which reduces calcium absorption and influences its release from the bones. Sodium citrate and sodium bicarbonate also have similar effects, but they can cause other problems like high uric acid levels or worsen high calcium levels in your urine.
Monitoring your urinary citrate and pH levels regularly is important and can be done with simple tests. While initially you might need to do this frequently, the frequency can decrease once your levels balance out. However, maintaining compliance with these tests and medication regimens can be challenging as they often don’t yield immediate benefits and the medications sometimes cause discomfort. It’s advisable to discuss potential issues with your healthcare provider to work out a manageable regimen.
In some specific cases, potassium citrate may not be suitable and alternatives may be needed. For example, in patients with gastric issues, liquid potassium citrate may be a better option as it is more quickly absorbed. In case of too much potassium in the blood, sodium bicarbonate may be used. Another alternative is potassium magnesium citrate, which has shown to be more effective than potassium citrate alone in raising pH and preventing kidney stones. However, it has not been extensively studied and optimal dosages are not yet established.
Achieving optimal levels of urinary citrate and the right level of pH in your urine can prevent kidney stone formation. It’s important to work closely with your healthcare provider to monitor these levels and adjust treatment accordingly.
What else can Hypocitraturia and Renal Calculi be?
If a person has low levels of citrate in their urine (hypocitraturia) and kidney stones (renal calculi), the doctor would need to evaluate several conditions that may cause these symptoms or look very similar. These conditions include:
- Use of medicine that inhibits carbonic anhydrase, a protein in our body
- Distal renal tubular acidosis, a condition that affects the kidney’s ability to maintain acid balance in the body
- High amounts of calcium in the urine (Hypercalciuria)
- High amounts of oxalate, a type of salt, in the urine (Hyperoxaluria)
- High amounts of uric acid, a waste product, in the urine (Hyperuricosuria)
What to expect with Hypocitraturia and Renal Calculi
People with low urinary citrate, a key factor in preventing kidney stones, can usually be treated with oral alkali therapy. This enhances the citrate levels in urine, which helps to prevent stone formation.
However, if a person has high potassium levels, a fast-moving intestinal tract, or discomfort in the digestive system, their use of potassium citrate could be limited. In such cases, alternatives like supplements with lower potassium or plain sodium bicarbonate can be considered. Liquid forms of these treatments can be used for those who have difficulty absorbing tablets.
For people with kidney stones who also have Irritable Bowel Syndrome (IBS), managing their bowel issues can often improve their condition.
Studies show that treatment with citrate can significantly lessen the formation of new stones. Without treatment, more than two-thirds of stone formers (69%) will continue to produce stones. But with optimal medical treatment, only 2% continue to form stones.
Compliance with taking citrate supplements can sometimes be less than ideal. After 6 months, only about 73.3% of patients stick with their prescribed regimen. The reasons for this vary. Some find the three-to-four-times-a-day dosage schedule difficult, some struggle with the large size of the tablets, and others experience negative side effects. Some patients also mistakenly believe the treatment is ineffective when they see “ghost” tablets in their stool — undissolved pieces of medication. Additionally, because patients may notice no immediate difference — good or bad — if they briefly stop treatment, they may not stick to the prescribed regimen.
Doctors should do their best to explain the long-term benefits of continuing therapy to their patients, even if there isn’t an obvious immediate clinical improvement and no apparent harm if the treatment is temporarily stopped. Having these discussions before starting therapy and at each yearly check is suggested. The good news is, with the right treatment, issues related to low citrate levels can be effectively managed, if not completely reversed. As a result, patients can look forward to significantly fewer new kidney stones while sticking to their citrate treatment plan.
Possible Complications When Diagnosed with Hypocitraturia and Renal Calculi
Taking potassium citrate can sometimes lead to high levels of potassium in the blood; this limits the amount that a patient can safely take. The therapy can also lead to several side effects, including an upset stomach, abdominal pain, and diarrhea. If urine continuously has a pH level higher than 7.2, calcium phosphate stones can form. Those with chronic kidney disease have a higher chance of too much potassium in their blood and should be carefully monitored.
Liquid forms of potassium citrate are often absorbed faster and better than tablets. However, some liquid options can cause more digestive system side effects, and many patients dislike the taste. Over-the-counter citrate supplements may be exceptions, as they claim to cause minimal stomach upset and have almost no taste.
Common Side Effects:
- High levels of potassium in the blood
- Upset stomach
- Abdominal pain
- Diarrhea
- Formation of calcium phosphate stones in urine with high pH
- Increased risk for patients with chronic kidney disease
Important Things to Remember:
- Liquid potassium citrate is usually better and faster absorbed than tablets
- Some liquid potassium citrate can lead to more digestive side effects
- The taste of liquid potassium citrate might be unpleasant
- Over-the-counter citrate supplements claim to cause less stomach upset and have minimal taste
Preventing Hypocitraturia and Renal Calculi
It’s crucial to take steps to address low urine citrate levels (hypocitraturia) and to prevent kidney stones (renal calculi) from forming. If kidney stones are left untreated, they can lead to serious health problems and can even be life threatening. Experts believe that half of all painful kidney stone issues could be avoided if the underlying chemical risk factors are identified and preventative treatment is started early on.
According to the American Urological Association (AUA), it’s important to tell everyone who has kidney stones about a special type of urine test that lasts 24 hours. This test can help to plan out preventative treatment, aiming to stop more kidney stones from forming in the future. As a result of this recommendation, more people with kidney stones are expected to undergo this test. Consequently, more patients will be identified as having low citrate levels in their urine.
Patients need to be aware of the importance of drinking plenty of fluids, making necessary changes to their diet, and understanding how citrate stops kidney stones from forming. This knowledge can significantly cut down the chances of kidney stones coming back. Patients should learn about the benefits of taking potassium citrate supplements and the necessity of regular check-ups to keep an eye on citrate levels in the urine and the overall health of the kidneys. Furthermore, making lifestyle changes like cutting down on sodium and animal protein intake can help to further lower the risk of kidney stones forming. By arming patients with important information and effective strategies, they can play an active role in their own treatment. In the long run, this can lead to better treatment results and can improve a patient’s overall quality of life.
