Calcium Stones: The First Steps in Treatment

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David A. Bushinsky, MD
David A. Bushinsky, MD

In industrialized countries, such as the United States, approximately 7%-13% of individuals will experience at least one episode of kidney stones over the course of their lifetime.

Approximately 80% of all kidney stones contain calcium (J Clin Invest. 2005;115:2598-2608). Calcium-based stones are composed primarily of calcium oxalate, calcium phosphate, or a combination of the two. We are beginning to understand the basic mechanisms that underlie stone formation.

This knowledge led to a number of well-controlled clinical trials demonstrating that several relatively simple interventions may dramatically reduce the incidence of recurrent stones. Eliminating or even decreasing the frequency of recurrent disease is one of the more gratifying aspects of being a physician.

Calcium oxalate or calcium phosphate crystals can form only in urine that is supersaturated with respect to the solid phase. The initial event in stone formation is termed nucleation, whereby ionic complexes coalesce to form a solid phase.

Once this solid phase is formed, stone growth may proceed in the supersaturated urine. If the initial phase and the bulk of the stone are composed of the same material, the process is termed homogeneous nucleation. If the remainder of the stone is composed of a different material, the process is termed heterogeneous nucleation. In nature, heterogeneous nucleation predominates.

In the case of calcium oxalate stones, calcium phosphate or uric acid crystals can serve as nucleation sites. Renal biopsy evidence indicates that in patients with calcium oxalate nephrolithiasis, the initial crystal phase forms in the interstitium around the thin limbs of the loop of Henle (J Clin Invest. 2003;111:602-605, 607-616). This calcium phosphate solid phase increases in size and finally erodes into the urinary space, forming a so-called Randall's plaque.

Calcium oxalate crystals may then form on the Randall's plaque by heterogeneous nucleation, increasing in size and finally breaking off into the urine. A stone that lodges in a ureter and obstructs urine flow results in the familiar symptoms of clinical stone disease, including pain and nausea.

However, the solid phase frequently passes painlessly without obstructing urinary flow. Urine contains inhibitors of both nucleation and growth that prevent stone formation even in supersaturated urine. As supersaturation increases, these inhibitors are overwhelmed and stone formation is more likely to occur.

The primary approach to preventing recurrent stone formation is to decrease urinary supersaturation with respect to the solid phase. For recurrent stone formers, a 24-hour urine collection is a critical step in guiding therapy. This collection should be sent to a laboratory that not only measures ionic concentrations and volume but calculates supersaturation as well. Most hospital laboratories are unable to perform all the analyses needed to determine supersaturation.

Once the results are known, interventions can be directed at the factors that lead to increased supersaturation, which should decrease the risk of stone formation. We will discuss a few of the most useful and straightforward interventions that can reduce stone formation in patients without a demonstrable metabolic disease, such as primary hyperparathyroidism or renal tubular acidosis.

Each of these interventions should be guided by urinary volume, ion excretion, and supersaturation. The composition of a kidney stone may also be used to guide therapy, especially when the results of the 24-hour urine collection are ambiguous.


Urine volume of stone patients is often less than desired because they frequently restrict their fluid intake either consciously (to avoid painful urination) or subconsciously. The concentration of the stone-forming components, and the resulting urinary supersaturation, is inversely proportional to the volume of urine.

We recommend that patients drink enough water to generate 2.5 liters of urine. In temperate environments, adults typically have roughly 0.8 liters of unmeasured daily water loss—termed insensible loss—primarily through respiration and perspiration. An individual who drinks 1.8 liters of water a day can be expected to produce about 1 liter of urine. If that same person increases his or her water intake to 2.8 liters per day, a 55% increase in intake, urine output will increase by 100% as insensible losses will remain relatively constant. Thus, an increase in water intake can result in a proportionately larger increase in urine output.

Individuals with higher insensible loss, such as lifeguards or farmers, will need to drink even more. Increasing urine output will decrease the concentrations of each of the stone-forming components and thus have a marked effect on supersaturation. In a five-year controlled trial, Borghi et al demonstrated that advising greater water intake significantly reduced stone formation (J Urol. 1996;155:839-843). Simply drinking more water to prevent stone formation is perhaps the most cost-effective therapy in medicine.


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