Abstract
Background/Aims: Renal stone disease may be seen as a clinical symptom of an underlying pathological process predisposing to crystallization within the renal tract. Renal stones may be comprised of calcium salts, uric acid, cystine and various other insoluble complexes. Nephrolithiasis may be the manifestation of rare single gene disorders or part of more common idiopathic renal stone-forming diseases. Methods and Results: Molecular genetics has allowed significant progress to be made in our understanding of certain stone-forming conditions. The molecular defect underlying single gene disorders often contributes to a significant metabolic risk factor for stone formation. In contrast, idiopathic renal stone formation relates to the interplay of environmental, dietary and genetic factors, with hypercalciuria being the most commonly found metabolic risk factor. Candidate genes for idiopathic stone formers have been identified using numerous approaches, some of which are outlined here. Despite this, the genetic basis underlying familial hypercalciuria and calcium stone formation remains elusive. The molecular basis of other metabolic risk factors such as hyperuricosuria, hyperoxaluria and hypocitraturia is being unraveled and is allowing new insights into renal stone pathogenesis. Conclusion: The discovery of both rare and common molecular defects leading to renal stones will hopefully increase our understanding of the disease pathogenesis. Such knowledge will allow screening for genetic defects and the use of specific drug therapies in order to prevent renal stone formation.
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2010
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