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Microlithiasis of the epididymis is a rare ultrasound finding in the general population, but the incidence of calcifications in various organs of patients with end-stage renal disease (ESRD) is extremely high. The aim of this study was to describe epididymal microlithiasis in 22 previously dialysed patients who received kidney transplantations at a median age of 19 years (range 9-30). The patients underwent scrotum ultrasonography, semen analysis and laboratory tests (renal function, sexual hormones, Ca, P and PTH) and were administered the International Index of Erectile Function questionnaire. Seventeen presented calcifications of the epididymis, two of whom had concomitant testicular calcifications; a further three patients had isolated testicular calcifications without epididymis involvement. It was not possible to investigate the fertility of all of the patients but 12 of the 13 whose semen was analysed showed abnormalities: five were azoospermic and seven oligospermic with various degrees of morphological anomalies. To the best of our knowledge, these are the first published data concerning the prevalence of epididymal calcifications in young dialysed patients undergoing renal transplantation. Epididymal microlithiasis and infertility were common findings and so performing a spermiogram and preserving semen before ESRD for future paternity may be good advice in this selected population., (© 2012 Blackwell Verlag GmbH.)

The steroids and xenobiotics receptor (SXR) up-regulates the expression and the synthesis of key enzymes in CyA metabolism. In this study, we examined the possible interactions between CyA exposure and SXR polymorphisms during the first year after renal transplantation. The study involved 66 pediatric renal transplant recipients (25 women and 41 men, mean age 13.9 ± 7.4 yr). All patients were genotyped for two sequence variations in the NR1I2 gene: g.-205_-200delGAGAAG and 7635 A>G. CyA trough levels and CyA weight-adjusted daily dose were recorded at 30, 90, 180, and 360 days after transplantation and compared between the different genotypes. A third newly discovered SXR polymorphism was characterized and also included in the study. CyA trough levels and CyA weight-adjusted daily dose were comparable on four time points throughout the first year post-transplant in all three groups. GEE showed a significant reduction in weight-adjusted CyA daily dose in patients carrying the deletion of 6 bp in SXR with a significant group-by-time effect that persisted also when analysis was corrected for age, prednisone dose, and acute rejection episodes. In our group of patients, only the g.-205_-200delGAGAAG SXR polymorphism was able to influence the metabolism of CyA continuously, during the first year after transplantation., (© 2012 John Wiley & Sons A/S.)

The main genes involved in the pharmacokinetics of immunosuppressive drugs are those encoding cytochrome P450 (CYP) family enzymes and multidrug resistance 1 (ABCB1). In this study, 87 Italian teenagers with transplanted kidneys (mean age 11.6 ± 4.8 years) receiving calcineurin inhibitors (CNIs) were genotyped for the single nucleotide polymorphisms (SNPs) CYP3A5*1/3 and CYP3A4*1B for CYP3A, and C1236T, G2677T/A, C3435T and IVS21+49 for ABCB1, and retrospectively evaluated for the influence of the screened SNPs on CNI blood level at different post-transplantation times. The CYP3A5*1 allele was present in 7% of the patients, and the CYP3A4*1B allele was present in 3% of patients. The ABCB1 C1236T, G2677T/A and C3435T SNPs C, G and T occurred frequently (55%, 53% and 54%, respectively). The frequency of the T allele of IVS21+49 was 86%. The frequency of SNPs in both genes was comparable with that reported in other European Caucasian populations but different from that found in Asians or Afro-Americans. None of the cyclosporine (CsA) pharmacokinetic parameters were associated with the CYP3A5 genetic polymorphism, whereas the presence of the A allele in some patients was responsible for the required administration of a significantly increased dose of tacrolimus (Tac) that was necessary to reach therapeutic target levels. None of the Tac pharmacokinetic parameters were associated with ABCB1 SNPs, but ABCB1 SNPs had early effects on the CsA exposure index and dose requirements. In conclusion, because SNPs of the CYP3A and ABCB1 genes may be associated with CNI pharmacokinetic parameters and exposure indices, pre-transplant genetic screening should be considered in order to avoid immunosuppressant-related adverse events.