Abstract. Recent developments in the genetics and physiology of cystinuria do not support the traditional classification, which is based on the excretion of cystine and dibasic amino acids in obligate heterozygotes. Mutations of only two genes (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC), have been found to be responsible for all three types of the disease. The ICC set up a multinational database and collected genetic and clinical data from 224 patients affected by cystinuria, 125 with full genotype definition. Amino acid urinary excretion patterns of 189 heterozygotes with genetic definition and of 83 healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9 carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II, 5.5%). This makes the traditional classification imprecise. A new classification is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2% in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2% in this series); and a possible third type, AB (1.6%), with one mutation on each of the above-mentioned genes. Clinical data show that cystinuria is more severe in males than in females. The two types of cystinuria (A and B) had a similar outcome in this retrospective study, but the effect of the treatment could not be analyzed. Stone events do not correlate with amino acid urinary excretion. Renal function was clearly impaired in 17% of the patients.

Renal function deterioration is a reason of concern in heart transplantation. Our aim was to evaluate long-term renal function in heart transplant children on cyclosporine (CsA) treatment and to investigate the effect of several variables possibly involved in renal function deterioration. Creatinine clearances were retrospectively reviewed in 50 children (median follow 99.7 months after heart transplant). Gender, age, and body weight at transplant, rejection episodes, CsA cumulative dose, and trough levels were analyzed. After an initial increase of the glomerular filtration rate (GFR), renal function worsened in most patients; 28% of the children developed renal insufficiency (defined as GFR <80 ml/min per 1.73 m2), which was already evident in the first 3 years. Neither CsA dose, trough levels, nor other patient characteristics were found to be associated with renal function deterioration. In this study renal failure occurred in one-third of the patients. The lack of association of CsA with renal insufficiency may be explained by several reasons, including the limitations of the retrospective design of the study. However, it is possible that the nephrotoxic effect of CsA is more likely to occur in a set of predisposed patients. These must be soon identified to evaluate early a calcineurin inhibitor-sparing strategy.

with the radioisotopic clearance, chosen as the gold standard in renal function assessment. In the first case, the creatininebased formulas overestimated glomerular filtration, in keeping with previous reports (3)(4). In the second case, urea clearance underestimated renal function, presumably because of a combination of low urinary output and circulating volume depletion. In both, the correct quantification of renal function was crucial: in the first patient, relying on creatinine clearance could impair a timely start of dialysis; in the second, urea-based calculations would probably support an abstention-based therapeutic approach.These two examples of pathophysiologic mechanisms potentially biasing functional assessment in the failing graft suggest the need to explore, in a larger patient series, the use of radioisotopic clearances in patients with discrepant data on the usual renal functional tests.

Like cyclosporine (CsA), tacrolimus acts through the inhibition of renal phosphatase calcineurin. CsA induces reversible vasoconstriction, causing a transient reduction of renal plasma flow in patients with renal transplantation. The aim of this study was to determine the effect of tacrolimus on renal plasma flow in renal transplanted children. Eight children were studied with a median age of 10.6 years, a mean glomerular filtration rate (inulin clearance) of 55 ml/min per 1.73 m2 (range 29-95), and a mean follow-up after transplantation of 5.6 months. Effective renal plasma flow (ERPF) was studied in each patient for 12 h after tacrolimus administration. Clearances were obtained every 2 h for 12 h after drug administration. Tacrolimus pharmacokinetics was also studied. Average ERPF at the start of the test was 289 ml/min per 1.73 m2 (range 177-404, SD +/- 106). Variation in each of the 2-h periods was not significant, although a mild reduction of plasma flow was observed in three of the eight children. No correlation was found between tacrolimus AUC, peak, or trough levels and renal blood flow variations. Despite the relatively small number of patients studied, these data suggest that, in vivo, a therapeutic oral dose of tacrolimus is not necessarily followed by a significant reduction of ERPF in renal transplanted children.

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