[Future perspective on the prevention of nephrolithiasis].
Renal stone formation has been explained by the physicochemical theory; i.e., nucleation, growth and aggregation of crystals in the urine. Current medical prevention is based on this theory and seeks to modulate promoters and inhibitors of stone formation. Recent studies have identified increasing numbers of macromolecular inhibitors such as glycosaminoglycans, bikunin, osteopontin and urinary prothrombin F1. These appear to be more important than low-molecular inhibitors like citrate. On the other hand, many investigators have focused on the role of tubular epithelial cells in stone formation. While crystal retention in the nephron has been considered necessary for stone formation, we and others have found that calcium oxalate crystals can bind to renal epithelial cells. Moreover, available evidence suggests that oxalate and/or calcium oxalate crystals can damage renal epithelial cells and enhance crystal binding. Concurrently, oxalate exposure induces genes coding macromolecular inhibitors, which are supposed to be a protective mechanism against stone formation. Thus, understanding of the mechanisms involved in kidney stone formation could lead to new therapeutic approaches to preventing stone recurrence. However, clinical application of the prophylactic approaches proposed here awaits further progress in basic research using rapidly growing new technologies. Application of the DNA microarray technique to the rat stone model may provide a clue to understanding stone forming process at the genetic level. In addition, case-control association analysis using single nucleotide polymorphism as a marker may be useful for detecting susceptibility genes in patients with calcium stone disease.
Department of Urology, Wakayama Medical University.
Yasuo
Y
Kohjimoto
Toshiaki
T
Shinka
Shigeyoshi
S
Morimoto
Masaya
M
Nishihata
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D002129:Calcium Oxalate / Q000378:metabolism; D002951:Citrates / Q000627:therapeutic use; D004326:Drinking; D020869:Gene Expression Profiling; D017781:Genes, Immediate-Early; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry / Q000209:etiology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020624:Oxalobacter formigenes; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D055502:Secondary Prevention
D002951:Citrates; D002129:Calcium Oxalate; D000493:Allopurinol