American Journal of Physiology. Renal Physiology vol:299 issue:5 pages:F905-F916
Renal proximal tubules are highly sensitive to ischemic and toxic insults and are affected in diverse genetic disorders, from which nephropathic cystinosis is the most common one. The disease is caused by mutations in the CTNS gene, encoding the lysosomal cystine transporter cystinosin, and is characterized by accumulation of cystine in the lysosomes throughout the body. In the majority of the patients this leads to generalized proximal tubular dysfunction (also called DeToni-Debré-Fanconi syndrome) in the first year and progressive renal failure during the first decade. Extra-renal organs are affected by cystinosis as well, with clinical symptoms manifesting mostly after 10 years of age. Cystine depleting agent cysteamine significantly improves life expectancy of patients with cystinosis, but offers no cure, pointing to the complexity of the disease mechanism. In this review, current knowledge on the pathogenesis of cystinosis is described and placed in perspective of future research.