Pharmacotherapy of Urolithiasis

Evidence From Clinical Trials

Orson W Moe; Margaret S Pearle; Khashayar Sakhaee

Disclosures

Kidney Int. 2011;79(4):385-392. 

In This Article

Abstract and Introduction

Abstract

Urolithiasis is a worldwide problem with significant health and economic burdens. Medical therapy that alters the course of stone disease has enormous medical and financial impact. Urolithiasis is a final manifestation of a broad range of etiologies and pathogenesis. The modest progress in understanding the pathophysiology has hampered successful development of targeted therapy. Current regimens are based mostly on rational alteration of urinary biochemistry and physical chemistry to lower the risk of precipitation. In terms of pharmacotherapy, there are drugs to successfully improve hypercalciuria, hypocitraturia, aciduria, hyperuricosuria, and hypercystinuria. These agents have been proven to be effective in randomized controlled trials in improving urinary biochemical and physicochemical risk factors, as well as clinical outcomes. Although our current regimens have clearly improved the management and lives of stone formers, there are still clearly identifiable immense voids in the knowledge of pathophysiology of stone disease that can be filled with combined basic science and clinical studies.

Introduction

Urolithiasis is a global problem spanning all geographic regions with an estimated annual incidence of 1%, prevalence of 3–5% and a lifetime risk of 15–25%. Once afflicted, urolithiasis tends to be recurrent in the majority of cases. According to data from the Urological Diseases in America Project, the total annual cost of nephrolithiasis in the United States in the year 2000 was about $5.3 billion. This underscores the toll taken by this disease on working-age individuals and society at large. Given the high cost of urgent medical treatment and/or surgical intervention, the attractiveness of a medical prophylactic program to reduce stone occurrences or increase the likelihood of successful conservative management of an acute-stone event is obvious. Indeed, simple medical management strategies utilizing inexpensive drug therapies have been shown to be efficacious and cost effective.[1] A retrospective study of patients followed for up to 20 years has shown sustained efficacy of medical therapy in the improvement of biochemical parameters and clinical events.[2]

Although there is steady improvement in therapy with shock-wave therapy and endourological techniques, the advance of medical therapy has been rather modest. From an etiological and pathophysiological point of view, it is important to emphasize that urolithiasis is a mere final manifestation of diverse and systemic etiological and pathogenic events. A major hurdle in this field in the past and present is the fact that the development of specific targeted therapy has been handicapped by the relative slow progress in unraveling pathophysiology. Current medical approaches are based on carefully constructed and rational modification of urinary biochemistry and physical chemistry to lower stone risk rather than etiology. This brief review is not meant to discuss the pathophysiology of urolithiasis, but rather provides a summary of the existing clinical data on medical therapy. Prospective randomized controlled trials will be highlighted, whereas uncontrolled and retrospective studies will be mentioned. Dietary and life style modifications and surgical therapy are not covered in this review. Because of the space limitation, complete and exhaustive citation is not possible.

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