Renal stones: from metabolic to physicochemical abnormalities. How useful are inhibitors?
Despite intensive studies in the last decades many aspects of nephrolithiasis still remain to be elucidated. Supersaturation with respect to lithogenic substances explains stones composed of cystine, uric acid, struvite, and calcium stones secondary to systemic diseases. In this subset there is a clear separation between patients and controls, and stone activity is well related to alterations in the physicochemistry of the urine environment. The understanding of the mechanisms of idiopathic calcium nephrolithiasis, on the other hand, is controversial, because we are still unable to establish clear-cut cause-effect relations between metabolic and physicochemical abnormalities and stone formation. Recent studies have been centered on the kidney, not only as the end organ of biochemical derangements due to systemic or environmental factors, but also as a complex laboratory where some events conduct to and others defend from lithogenesis. Many of these phenomena occur in the proximal tubule. Molecular biology has explained some types of hypercalciuria, which are due to genetic mutations altering tubular function, and similar results are expected for hypocitraturia and hyperoxaluria. The latter is conducive to stone formation through several mechanisms including supersaturation, oxidative stress on tubular cells, and interference with some natural inhibitors. The long list of inhibitors includes ionic and macromolecular moieties, some being produced within the nephron in response to lithogenic insults, and some affecting not only crystallization but also crystal cell adherence. Crystal trapping is believed to anticipate a renal stone. However, much has still to be clarified on their actual role in calcium nephrolithiasis, by what mechanisms they act, if patients and controls differ in the excretion and structure of some inhibitors, and whether differences are genetically determined.
Marangella
M
M
Nephrology, Dialysis and Renal Stone Unit, Mauriziano Umberto I Hospital, Turin, Italy. mmarangella@mauriziano.it
Vitale
C
C
Petrarulo
M
M
Bagnis
C
C
Bruno
M
M
Ramello
A
A
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D006801:Humans; D007669:Kidney Calculi / Q000209:etiology* / Q000517:prevention & control*; D008659:Metabolic Diseases / Q000150:complications*; D008954:Models, Biological; D014556:Urine / Q000737:chemistry*