[Inherited monogenic kidney stone diseases: recent diagnostic and therapeutic advances]

Hereditary monogenic kidney stone diseases are rare diseases, since they account for nearly 2% of nephrolithiasis cases in adults and 10% in children. Most of them are severe, because they frequently are associated with nephrocalcinosis and lead to progressive impairment of renal function unless an early and appropriate etiologic treatment is instituted. Unfortunately, treatment is often lacking or started too late since they are often misdiagnosed or overlooked. The present review reports the genotypic and phenotypic characteristics of monogenic nephrolithiases, with special emphasis on the recent advances in the field of diagnosis and therapeutics. Monogenic stone diseases will be classified into three groups according to their mechanism: (1) inborn errors of the metabolism of oxalate (primary hyperoxalurias), uric acid (hereditary hyperuricemias) or other purines (2,8-dihydroxyadeninuria), which, in addition to stone formation, result in crystal deposition in the renal parenchyma; (2) congenital tubulopathies affecting the convoluted proximal tubule (such as Dent's disease, Lowe syndrome or hypophosphatemic rickets), the thick ascending limb of Henlé's loop (such as familial hypomagnesemia and Bartter's syndromes) or the distal past of the nephron (congenital distal tubular acidosis with or without hearing loss), which are frequently associated with nephrocalcinosis, phosphatic stones and extensive tubulointerstitial fibrosis; (3) cystinuria, an isolated defect in tubular reabsorption of cystine and dibasic aminoacids, which results only in the formation of stones but requires a cumbersome treatment. Analysis of stones appears of crucial value for the early diagnosis of these diseases, as in several of them the morphology and composition of stones is specific. In other cases, especially if nephrocalcinosis, phosphatic stones or proteinuria are present, the evaluation of blood and urine chemistry, especially with regard to calcium, phosphate and magnesium, is the key of diagnosis. Search for mutations is now increasingly performed in as much as genetic counselling is important for the detection of heterozygotes in autosomic recessive diseases and of carrier women in X-linked diseases. In conclusion, better awareness to the rare monogenic forms of nephrolithiasis and/or nephrocalcinosis should allow early diagnosis and treatment which are needed to prevent or substantially delay progression of end-stage renal disease. Analysis of every first stone both in children and in adults should never be neglected, in order to early detect unusual forms of nephrolithiasis requiring laboratory evaluation and deep etiologic treatment.