Alpha lipoic acid as a novel therapeutic approach to cystinuria

ABSTRACT

Introduction: Cystinuria is a rare form of kidney stone disease inherited through mutations in the cystine transporter genes SLC3A1 and SLC7A9. Patients suffer from frequent and painful renal cystine calculus formation necessitating repeated radiation exposure, hospitalizations and surgical interventions. Available dietary and pharmacologic managements are burdensome to patients due to the sheer volume of pills and fluid that must be consumed and display limited efficacy.

Areas Covered: The epidemiology, pathophysiology, and currently available options for dietary and pharmacological management including hyperhydration, modification of urinary pH, organosulfur drugs and crystal Inhibitors are reviewed. A novel drug in clinical trials, alpha lipoic acid (ALA), is presented and its hypothesized mechanism of action reviewed.

Expert Opinion: A novel potential therapy, alpha lipoic acid, has been strikingly effective when used in a knockout mouse model. This compound is available over the counter as a food supplement, has been used in multiple human trials for other disease processes and has been shown to be safe and well tolerated. The promise of ALA is to reduce the burden of medications, stone events, surgical interventions, and financial concerns in cystinuric patients.

KEYWORDS:

• Alpha Lipoic Acid
• Cystinuria
• Nephrolithiasis
• Penicillamine
• Tiopronin

Article Highlights

• Cystinuria is a rare kidney stone disease caused by autosomal mutations in cystine transporter genes SLC3A1 and SLC7A9.

• Available therapies (hyperhydration, urinary pH modification, tiopronin, and penicillamine) are burdensome and display limited efficacy.

• Alpha Lipoic Acid is a safe and well tolerated food supplement that has been remarkably effective in a mouse model of cystinuria. This compound is currently in human clinical trials.

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Declaration of interest

MLS is a founding member of Applaud Medical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.