Optimizing metabolism: eat right for your type: laboratory testing to guide kidney stone prevention.
Half of the 1 in 10 Americans who experience a kidney stone have a recurrence. Research shows that diet can do a lot toward prevention. My column in the July 2011 Townsend Letter presented emerging evidence on how diet and fluid intake can prevent kidney stones. However, many of the strategies are specific to the type of kidney stone. This column explains how to identify a patient's type of kidney stone.
Most patient information flyers put "drink lots of water" on the top of the kidney stone prevention list. The strongest dietary recommendation that emerged from studies has been hydration - not necessarily because it is the most powerful intervention, but because it works for all stones. That's the key. Hydration works for all stones. But it isn't as effective as the right diet for preventing the right stone type. Hydration also doesn't specify what one should hydrate with; the type of fluids that one should use is specific to the type of kidney stone.
Some dietary interventions can help prevent one type of kidney stone and potentially contribute to causing another type. Adding lemon or restricting salt are examples of dietary interventions that can help certain types of stones and make other stones worse.
Unfortunately, most research on dietary interventions until recently has combined all types of stones. Nutritional treatments that are stone-specific were therefore not detected. You can see how the law of averages may be at work in large population studies that don't distinguish among the type of kidney stones.
The simplest and most reliable way to determine kidney stone type is to send the stone to a lab for analysis. If a patient brings in the stone on a follow-up visit or it is retrieved in the hospital, by all means identify what stone it is, because the answer is but a stone's throw away. Don't throw it away. If the opportunity presents itself the first time, analyze it. The "old school" approach was to test only the stones from someone with recurrence.
A stone is hard to retrieve. It forms in the kidney and causes pain as it travels down the corresponding ureter because that is the tightest squeeze. The journey through the bladder and the urethra can take several days and can alter the stone. Some crystals that form stones dissolve upon medical treatment.
Some urologists are removing kidney stones by endoscopy for various reasons. One advantage to this method is being able to obtain the stone for laboratory analysis.
Another barrier to getting stones analyzed has been the lingering question, do people always get the same type of stone? There is the rare report of the single individual with different types of kidney stones, even concurrently. However, in general, an individual with recurrence experiences the same type. Furthermore, if there is a family history of kidney stones, the stone is likely to be the same type that occurred in other family members.
Clinical Clues to Stone Type
Before a stone has been retrieved and analyzed, clinicians can determine what type of patient is most likely to have. This working hypothesis can help guide treatment until a more definitive answer is available. Data on who gets what can guide clinical decision-making, especially in the absence of the stone to analyze. Table 1 gives an overview:
Table 1: Distribution of Kidney Stone Types by Age Type of Children Adult stone % % Calcium 45-65 56-61 Oxalate Calcium 24-30 8-18 * Phosphate Uric Acid 2-4 9-17 Struvite 7-13 2-4 Cystine 5-8 1 Other 4 2 * Incidence as high as 75% in pregnant women (22)
* Calcium oxalate stones are the most common type among adults.
* Stones are more likely to be calcium phosphate in children and pregnant women
* Children are more likely to have undiagnosed structural abnormalities that can predispose to both infections and struvite stones. Children are also more likely to have undiagnosed metabolic abnormalities that can be associated with cysteine stones.
* With a clinical history of insulin resistance or gout, the likelihood of uric acid stones goes up.
* A recent course of antibiotics or gastrointestinal infection may be associated with calcium oxalate stones because of a reduction in microorganisms that reduce uptake of oxalate. Several other medications can predispose to certain types of stones.
* Abuse of ammonium-containing laxatives can lead to the rare ammonium urate stones.
* In other countries, contamination of infant formula with melamine has led to kidney stones with identifiable melamine crystals.
Since kidney stones track within families, is there a genetic test to guide prevention? There is no doubt that genetics stacks the deck on kidney stones. However, right now and in the foreseeable future, the best genetic test is a phone call to the family member with a known stone type to find out what kind it is.
Clinical genetic testing is not on the horizon because most links are polygenic with variable effects on phenotype, such as the case with high urinary excretion of calcium. Other familial associations may relate to colonization with similar gastrointestinal flora rather than common genetics.
That said, monogenetic links such as mutations in the ion transporters are of primarily research interest to identify potential drug therapies, and can also corroborate dietary recommendations. Therefore, when the occasional patient has a known family genetic history, this can be useful to guide prevention recommendations, but not to the exclusion of more common risk factors.
Another way to approach kidney stone type is to analyze the urine, which creates the chemical predisposition for stone formation. If you think of the kidney stone as a bullet, consider the urine characteristics to be the smoking gun. Even if the bullet is not retrievable, the urine characteristics elaborated in this column inform dietary recommendations.
The urine characteristics are best assessed shortly after the kidney stone has passed. Urine is collected for 24 hours and should be a volume of at least 2 liters. The specific gravity and urine pH can be measured when urine is collected for a shorter period of time. However, having the average over a 24-hour period of time provides additional clinical information.
Urine Specific Gravity > 1.015
A higher value suggests dehydration. The more concentrated the urine, the more likely a stone can form. How someone should hydrate is guided by what type of stone they have.
CaOx and uric acid stones tend to form at lower urine pH - raising urine pH by dietary changes or oral base (e.g., citrate) supplementation is recommended. CaP and struvite stones tend to form at higher urine pH - lowering urine pH by dietary changes or oral acid such as betaine or cranberries.
Test for the following urine characteristics in calcium oxalate stones or if stone type is unknown:
High oxalate (> 40 mg/24 hrs)
If this is elevated, eat moderate fruits and vegetables. Do not restrict calcium. Consider magnesium oxide or magnesium citrate supplementation. Oxalate restriction is minimally effective and probably applies primarily to those few with genetic mutations in the oxalate transporters. Encourage moderate vitamin C intake by dietary sources rather than supplements, since vitamin C can raise oxalate.
If the kidney stone is associated with antibiotics, the high oxalate level may be due to depletion of the microbial flora. A select strain of gut bacteria uses oxalate as substrate, thereby reducing the intestinal absorption. In the absence of these organisms, more oxalate is absorbed and subsequently excreted in the urine.
High calcium (mg Ca/g Cr)
A high calcium is defined as follows: child (1 month-17 years), >0.8; adult male, >210; adult female, >275. Reduce calcium with sodium restriction to 2 g/24 hours or less. Do not restrict calcium intake below recommendations for age and gender.
Low magnesium (< 70 mg/24 hrs)
Increase dietary sources of magnesium when low and consider supplementation with magnesium oxide or magnesium citrate.
Low citrate (< 100 mg/24 hrs)
Consider calcium citrate or magnesium citrate supplementation. Lemon water (lemon or lime wedge in water) is encouraged.
Low phytates (PPi < 3.8 mg/L;IP6 < 0.4 mg/L)
Higher intake of fiber may be appropriate if phytates are low, but this can also represent an increase in oxalate.
Weight is important, since excess weight, especially fat weight, increases kidney stone risk. Several blood tests are appropriate following kidney stones and can help better define both stone type and risk factors. Markers for insulin resistance and kidney function are recommended, since both kidney stones and diabetes are risk factors for chronic kidney disease. A serum Ca > 10 mg/dL could point to kidney stones from hyperparathyroidism, which should be considered. Monitoring vitamin D levels is prudent because both too little and too much vitamin D can increase kidney stone risk. Elevated uric acid levels can be managed with diet and are associated with uric acid stones. Blood levels of medications potentially associated with kidney stones may be applicable as well.
Laboratory analysis of the kidney stone and urine allows patients to derive the most benefit from food and nutrient interventions. A family history of kidney stone occurrence, a medical history, and select blood tests may additionally inform food and nutrient recommendations.
Those interested in an academic review article on the topic and on earning continuing professional education credits may refer to my coauthored review in American Family Physician (Dec. 1, 2011).
Ingrid Kohlstadt MD, MPH, has been elected a Fellow of the American College of Nutrition and the American College of Preventive Medicine, and is an associate at the Johns Hopkins Bloomberg School of Public Health, She recently completed a two-year appointment at the FDA working in the Office of the Commissioner, and published one of Medscape Public Health's "Top Ten CMEs for 2010." Dr. Kohlstadt is the founder and chief medical officer of INGRIDients Inc., editing Food and Nutrients in Disease Management (CRC Press; Jan 2009) and Scientific Evidence for Musculoskeletal, Bariatric and Sports Nutrition (CRC Press; 2006).
by Ingrid Kohlstadt MD, MPH