¹Department of Internal Medicine, Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

Correspondence: Khashayar Sakhaee, Department of Internal Medicine, Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center at Dallas, 3523 Harry Hines Blvd, Dallas, Texas 75390-8885, USA. E-mail: Khashayar.Sakhaee@UTSouthwestern.edu

Received 15 August 2008; Revised 14 October 2008; Accepted 21 October 2008; Published online 10 December 2008.

Abstract

Over the past 10 years, major progress has been made in the pathogenesis of uric acid and calcium stones. These advances have led to our further understanding of a pathogenetic link between uric acid nephrolithiasis and the metabolic syndrome, the role of Oxalobacter formigenes in calcium oxalate stone formation, oxalate transport in Slc26a6-null mice, the potential pathogenetic role of Randall's plaque as a precursor for calcium oxalate nephrolithiasis, and the role of renal tubular crystal retention. With these advances, we may target the development of novel drugs including (1) insulin sensitizers; (2) probiotic therapy with O. formigenes, recombinant enzymes, or engineered bacteria; (3) treatments that involve the upregulation of intestinal luminal oxalate secretion by increasing anion transporter activity (Slc26a6), luminally active nonabsorbed agents, or oxalate binders; and (4) drugs that prevent the formation of Randall's plaque and/or renal tubular crystal adhesions.