AFM reveals mechanisms of kidney stone formation

Kidney stones can cause unimaginable pain. Understanding why some become too large to pass through the urinary system could lead to lifestyle recommendations and treatments that could prevent them from forming.

Kidney stones consist primarily of crystallized calcium oxalate monohydrate, and they generally form when there is a high concentration of calcium and oxalate in urine. However, kidney stone formation is not that simple because healthy people usually have a high concentration of calcium and oxalate in their urine. In a review of calcium oxalate monohydrate crystal growth, the authors wrote that atomic force microscopy (AFM) is the only technique that can show real-time crystal growth in solution at both molecular and microscopic levels. The reviewers were affiliated with Lawrence Livermore National Laboratory in California and with the University of Pennsylvania.

In situ AFM can reveal morphological features of crystals during growth. These calcium oxalate crystals have three major crystal faces that have steps resembling those that lead to the top of an Aztec or Nepalese temple. Each step grows until it reaches a critical size, and then a new step forms.

Citrate, a small molecule, and osteopontin, a protein, strongly inhibit calcium oxalate monohydrate crystal formation at levels normally found in urine. In situ AFM revealed that citrate and osteopontin cause this inhibition by binding to the steps on specific crystal faces, resulting in major changes in crystal morphology.

The reviewers reported that AFM is a promising way to examine other medical conditions caused by crystal formation. They predict that the technique will lead to new therapies for such conditions as computers become more powerful and as the method becomes more mainstream. (American Journal of Physiology-Renal Physiology, December 2006, pp. F1123-F1131.)