Metabolic evaluation of kidney stone formers, "Beyond the Abstract," by Omotayo Arowojolu

BERKELEY, CA ( - In our recent review article, we state that kidney stones are preventable. Yet many patients do not receive any specific evaluation or counseling beyond “drink a lot of fluids.” In order to predict the occurrence of stones and prescribe preventative measures, a thorough patient history and laboratory evaluation are essential. Family, social, and diet histories can all give insight into the pathogenesis of stone formation and whether a patient is at risk for future stones.

Although the literature has attempted to tease out when metabolic evaluation is needed, we have concluded that metabolic evaluation is almost always useful, if not necessary. The 24-hour urine collection allows the physician to prescribe preventative medications and make recommendations that are specific to the patient’s urine chemistry. The 24-hour urine collection is often reserved for recurrent stone formers; however it may be beneficial in first-time stone formers with additional co-morbidities such as diabetes, high blood pressure, and the metabolic syndrome. Type 2 diabetes patients have an increased risk for future uric acid stone formation. Concurrently, uric acid stone formers have a higher prevalence of Type 2 diabetes (compared to calcium stone formers).[1] Insulin resistance, a feature of metabolic syndrome, impairs renal ammonia synthesis resulting in acidic urine, which favors the production of uric acid stones.[2] It is also possible that diabetes increases the risk of calcium stones, but data proving that are currently lacking.

Dietary and pharmacological preventative measures are effective in lowering stone formation. Low urine volume is a frequent finding and often is effective if increased fluid intake leads to urine volumes of at least 2.5L per day. The only previous randomized trial of a diet effective in preventing calcium stones showed that normal calcium intake, combined with restriction of dietary sodium, animal protein, and oxalate, was associated with a 50% reduction in stone occurrence after 5 years, in Italian men.[3] Recently the Dietary Approaches to Stop Hypertension (DASH) diet was shown to have possible benefit for stone prevention. Designed as a healthy way of eating to prevent or treat hypertension, the diet is high in fruits, vegetables, and whole grains, low in sodium, cholesterol and saturated fats and allows red meat and sweets in moderation. Although formulated to reduce blood pressure, Taylor et al. investigated the effects of this diet on stone risk and 24-hour urine composition.[4] Using a DASH score to quantify the level of adherence to a DASH-style diet, the study determined that a higher DASH score was associated with a decrease in kidney stone risk.[4, 5] Urine citrate excretion and volume were higher. In conclusion, for dietary prevention of stones, calcium restriction is not appropriate. Urinary calcium excretion is best limited by lowering sodium intake.

Medications for kidney stone prevention control the acidity, volume, and mineral composition of the patient’s urine. Thiazide diuretics are useful for prevention of calcium stones because they cause renal reabsorption of calcium and reduce urinary calcium excretion. Allopurinol, a xanthine oxidase inhibitor, reduces uric acid excretion in the urine, which is associated with prevention of calcium stones. Alkalinization of the urine, with potassium citrate, not treatment with xanthine oxidase inhibition, is the first choice for uric acid stones.[6] Febuxostat, a newer xanthine oxidase inhibitor, may also be useful for calcium stone prevention, since it is an alternative to allopurinol for patients with hyperuricosuria.[7] Goldfarb et al. performed a randomized controlled trial of febuxostat versus allopurinol or placebo and observed that in 6 months, febuxostat lowered 24-hour uric acid excretion, significantly (P=0.003) more than allopurinol treatment or the placebo. However, at 6 months, there was no significant reduction in the number of stones or in the size of the pre-existing radio-opaque stone present at study entry. Perhaps a longer study of at least 3 years would be required to demonstrate if febuxostat is as efficacious, or superior to, treatment with allopurinol.

Although diet (Borghi et al.,[3] and perhaps DASH) and medications (thiazides, citrate, allopurinol) are effective, they have never been compared to each other head to head. They may both have advantages and disadvantages in varying patient populations. Diet allows for customization for each patient and avoids certain adverse effects of medications, but may be more difficult to adhere to. Medications have adverse effects and interactions with other therapies and diet, but may require less life style alteration.

Most important is that patients are given information and evaluation regarding the varying options and are told that kidney stones are preventable.  


  1. Daudon, M., Traxer, O., Conort, P., Lacour, B. & Jungers, P. Type 2 diabetes increases the risk for uric acid stones. Journal of the American Society of Nephrology: JASN, 2026-2033, doi:10.1681/ASN.2006030262 (2006).
  2. Abate, N., Chandalia, M., Cabo-Chan, A. V., Jr., Moe, O. W. & Sakhaee, K. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney International, 386-392, doi:10.1111/j.1523-1755.2004.00386.x (2004).
  3. Borghi, L. et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. New England Journal of Medicine, 77-84, doi:10.1056/NEJMoa010369 (2002).
  4. Taylor, E. N., Stampfer, M. J., Mount, D. B. & Curhan, G. C. DASH-style diet and 24-hour urine composition. Clinical Journal of the American Society of Nephrology : CJASN 5, 2315-2322, doi:10.2215/CJN.04420510 (2010).
  5. Taylor, E. N., Fung, T. T. & Curhan, G. C. DASH-style diet associates with reduced risk for kidney stones. Journal of the American Society of Nephrology: JASN, 2253-2259, doi:10.1681/ASN.2009030276 (2009).
  6. Ettinger, B., Tang, A., Citron, J. T., Livermore, B. & Williams, T. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. New England Journal of Medicine, 1386-1389, doi:10.1056/NEJM198611273152204 (1986).
  7. Goldfarb, D. S., Macdonald, P. A., Gunawardhana, L., Chefo, S. & McLean, L. Randomized Controlled Trial of Febuxostat Versus Allopurinol or Placebo in Individuals with Higher Urinary Uric Acid Excretion and Calcium Stones. Clinical Journal of the American Society of Nephrology: CJASN, doi:10.2215/CJN.01760213 (2013).

Written by:
Omotayo Arowojolu as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

MD/PhD candidate, New York University School of Medicine, New York, NY USA

Metabolic evaluation of first-time and recurrent stone formers - Abstract

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