Eight surgeries and 10 visits to the emergency department – that is not an atypical record for the annual number of hospital encounters for one of our 42 active cystinuric patients, an orphaned disease characterized by the rapid formation of symptomatic recurrent kidney stones. Cystinuria is an autosomal recessive disorder that prevents resorption of cystine from urine. Supersaturation of cystine in the urine produces unique hexagonal crystals that precipitate and form stones in the kidney that frequently result in ureteral/renal obstruction, infection, and chronic kidney disease. With an estimated prevalence of 1:15,000 (less than 200,000 in the United States) these patients face multiple challenges managing these unexpected episodes of acute and chronic pain. First, cystine kidney stone recurrence rates are extraordinarily high and result in a lifetime of waiting for the next unanticipated acute episode of pain requiring emergent medical attention and frequent surgical interventions. Rates of chronic kidney disease and hypertension are also higher in cystinuric patients. Second, current treatment regimens, which include aggressive daily fluid hydration (resulting in voiding up to 3-4 liters per day) and numerous medications (typically 6 tablets of potassium citrate and 8-12 tablets of tiopronin per day), have limited effectiveness. Third, as with most orphan diseases, little investment has been made in developing new treatments for cystinuria, and no new medication has been introduced into clinical practice in more than 30 years. Cystinurics are desperate for a new treatment regimen that will decrease the need for surgical intervention, decrease painful spontaneous stone passage, and improve their chronic and intermittent acute pain.
Alpha-lipoic acid (referred to hereafter as lipoic acid) is a thiol-containing naturally-occurring compound. It is sold as an over-the-counter supplement and an antioxidant that is produced endogenously and involved with mitochondrial energy metabolism as an enzyme cofactor. In a knockdown mouse model for cystinuria, kidney stones form at a rapid rate by 2-3 months of age for mice fed standard food. We have shown that administration of lipoic acid nearly eliminates stone formation when fed to the mice at an early age; stone growth in cystinuric mice is also dramatically blunted when given after stones have already started to form. Given its well-established safety profile in humans and its powerful treatment effect in mice, we propose a clinical trial of lipoic acid for patients with cystinuria to reduce stone recurrence/growth and need for surgical intervention, and to improve their overall quality of life.
With a robust population of more than 1300 nephrolithiasis patients seen annually in our established (>30 years) stone center among which we have 42 actively treated patients with cystinuria, we are well-equipped to complete the proposed clinical study. Our research goal is to evaluate the efficacy of lipoic acid to reduce cystine kidney stone formation, need for surgical intervention, and ultimately improve the quality of life for patients with cystinuria.
For more information about this trial, and how to qualify for enrollment, please contact 415 353 2433.