INEFFECTIVENESS OF ASCORBIC-ACID THERAPY IN NEPHROPATHIC CYSTINOSIS

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R̂ = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08). (N Engl J Med 300:756–759, 1979) NEPHROPATHIC cystinosis is a metabolic disease that is inherited in an autosomal recessive manner and is characterized biochemically by a high intracellular content of free (nonprotein) cystine within lysosomes. Children with this disorder appear normal at birth, but by six to nine months of age have symptoms of renal tubular dysfunction termed the renal Fanconi syndrome. Despite symptomatic treatment, the children grow poorly and a progressive fall in glomerular filtration rate ensues that usually leads to end-stage renal disease before 10 years of age.1,2 Although the primary metabolic defect that leads to accumulation of free cystine within lysosomes is unknown,. © 1979, Massachusetts Medical Society. All rights reserved.