PATHOGENESIS OF IDIOPATHIC CALCIUM NEPHROLITHIASIS - UPDATE 1997

Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in West ern countries. The physicochemical theory of lithogenesis, which expla ins stone formation by the precipitation, growth, and crystalline aggr egation of lithogenic salts in the urine, has contributed greatly to t he understanding of the pathogenesis of calcium urolithiasis. However, several aspects are still unexplained; the co-existence of familial o ccurrence, primary tubular dysfunctions with ICN, and anomalies in the systemic handling of oxalate and calcium led to the development of a cellular hypothesis of ICN. A number of cellular defects in the handli ng of ions has been reported that involves both anion and cation trans port. These anomalies are probably the expression of a still. unknown cellular defect in idiopathic calcium stone formers. We suggested that an anomaly in the cell membrane composition might be responsible for the complex array of cell ion flux abnormalities observed in ICN. Rece ntly, a disorder in the n-6 polyunsaturated fatty acid series has been described; it is characterized by a lower linoleic acid content and a higher arachidonic acid concentration in both plasma and erythrocyte membrane phospholipids of renal calcium stone patients. This anomaly c ould cause an increased activity of ion carriers; furthermore, it may lead to increased prostaglandin synthesis and to secondary phenomena a t the kidney, skeletal, and intestinal level. As a consequence, critic al conditions for lithogenesis in the kidney may ensue. The data sugge st a common pathogenesis for hypercalciuria and hyperoxaluria. The sys temic defect in the phospholipid arachidonic acid level may be both of dietary or genetic origin; experimental data suggest that the increas e in delta-6 desaturase activity, the limiting enzyme in the metabolic pathway of polyunsaturated fatty acids, might be relevant to the path ogenesis of lipid abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its related problems (at the kidney, intestin al, and bone level). In conclusion, the review describes a unifying pa thogenetic hypothesis of nephrolithiasis that accounts for the many ce ll abnormalities observed in this disease, as well as the different cl inical-biochemical features observed in renal stone patients and expla ins the multisystemic manifestations described in ICN.