Idiopathic urinary stone disease: possible polygenic aetiological factors

Abstract

About 12% of men and 5% of women of Western European descent develop at least one urinary stone during their lifetime. The incidence is somewhat less in individuals of sub-Saharan African or Asian descent, although there is a high incidence in the Middle Eastern countries. Calcium oxalate is a major constituent of about 70% of these stones. They are of multifactorial origin, with both genetic and environmental factors involved. The genetic factors influence different components of a highly complex system whereby calcium oxalate, which has a very low solubility in water, remains in solution. When the system is perturbed, the calcium oxalate crystallizes, the crystals aggregate and stones form. The genetic factors operate through mechanisms that are less obvious than the environmental ones such as the patient's state of hydration and dietary effects on the concentrations of the relevant ionic species. It is now generally accepted that the crystallization process begins in the distal ducts of the kidney by adhesion of calcium and oxalate to the epithelial surfaces of the tubule cells and their internalization. The calcium oxalate crystal becomes detached, with some incorporated organic materials forming a microlith. This process of microlith formation could arise either because of genetically determined alterations in the surface properties of the cells, or in the composition and/or concentration of substances in the urine that inhibit crystal nucleation and/or aggregation. The microliths pass through the collecting tubules more slowly than calcium oxalate in simple physical solution, aggregating until they reach the pelvicalycial system, where they grow into stones and pass down the ureters. It has been suggested that a shift in the crystal form from the mono-hydrate to the di-hydrate form reduces the likelihood of such adhesion, and that molecular inhibitors of crystallization operate by favouring the dihydrate form.1 Calcium oxalate urolithiasis had, … Address correspondence to Dr R.W.E. Watts, Renal Section, Division of Medicine, Imperial College, London, Hammersmith Campus, Du Cane Road, London W12 0NN