**1. Introduction**

Nephrolithiasis is a common disease, typically occurring between 30 and 60 years of age. It is the most often‐diagnosed chronic condition involving the kidney, after hypertension. The symptoms and consequences are not life threatening for the majority of patients, but stones in the urinary tract are a major cause of morbidity, hospitalization, and days lost from work [1]. The incidence of nephrolithiasis is increasing. In Italy, for example, the number of patients given hospital treatment for this condition rose between 1988 and 1993 from 60,000 to 80,000 a year. About 12,000 patients a year required surgical treatment or urological maneuvers, and the number of extracorporeal shock wave lithotripsy sessions administered amounted to approximately 50,000 a year [2].

The metabolic characteristics of the urinary stones identified in patients with nephrolithiasis vary, but the most common (accounting for 75% of all cases) are calcium‐containing stones. Calcium oxalate (CaOx) is the primary component of most stones [3], often combined with some calcium phosphate (CaP), which may form the stone's initial nidus. Crystal retention in the kidney is essential to stone formation and this occurs with several different patterns of deposition in the kidneys of stone formers, each pattern being associated with specific types of stone. Patients with idiopathic CaOx stones have white deposits on their papillae called "Randall's plaque" [4]. Biopsies of these areas reveal interstitial deposits of CaP in the form of biological apatite, which first develop in the basement membrane of the thin loops of Henle and which contain layers of protein matrix. These deposits may extend down to the tip of the papilla and, if the overlying urothelium is denuded, the exposed plaque can become an attachment site for stones [5]. Stones seem to start as deposits of amorphous CaP overlying the exposed plaque, interspersed with urinary proteins. With time, more layers of protein and mineral are deposited, and the mineral phase becomes predominantly CaOx.

By contrast, in patients whose stones consist mainly of CaP (apatite or brushite), these stones are not attached to plaque. Instead, many collecting ducts fill with crystal deposits that occupy the tubule lumen and may protrude from the openings in the ducts of Bellini. Generally speaking, most stone formers studied to date have had crystal deposits in the med‐ ullary collecting ducts, with the exception of those with idiopathic CaOx stones, who have no intratubular deposits, but abundant deposits of apatite in the papillary interstitium.

Calcium nephrolithiasis, the most common renal form of stone disease, is defined as the for‐ mation of macroscopic concretions of inorganic and organic material in the renal calyces and/ or pelvis. Many *in vitro* and *in vivo* studies on the mechanisms underlying calcium nephroli‐ thiasis have produced evidence of this condition frequently being associated with nephrocal‐ cinosis, a condition involving microscopic renal crystal deposition.
