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.

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and antiinflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs + CpG. Inhibition is restored in CpG + MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4 + and CD8 + cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.

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Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

Little is known about the role of proteinuria in the progression of childhood renal diseases. We analyzed the decline in creatinine clearance ( C(Cr)) and kidney survival in 225 children (185 males) with chronic renal failure (CRF) due to isolated hypodysplasia or hypodysplasia associated with urological abnormalities. The data were based on the information available in the Italian Pediatric Registry of CRF (ItalKid Project), which includes patients from all of Italy aged <20 years with C(Cr )levels of <75 ml/min per 1.73 m(2). Patients aged <2 years and those with C(Cr )levels of <20 ml/min per 1.73 m(2) or a follow-up of <1 year were excluded from the analysis, as were those receiving angiotensin-converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8+/-4.2 years, a mean C(Cr )of 50+/-16.3 ml/min per 1.73 m(2), a median urinary protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02-7.21), and a mean duration of follow-up of 3.5+/-1.1 years. The patients were divided into three groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr <0.2) n=83; group B low (uPr/uCr 0.2-0.9) n=71; and group C mild (uPr/uCr >0.9) n=71. Patients in groups A and B showed a significantly slower decline in C(Cr )than those in group C (slope +0.16+/-3.64 and -0.54+/-3.67 vs. -3.61+/-5.47, P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs. 44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio ( P<0.01) and age ( P<0.0001) correlated with a faster decline in C(Cr )irrespective of baseline C(Cr). There was no correlation with mean arterial blood pressure. We conclude that proteinuria is an independent predictor of progression to end-stage renal failure also in children whose renal impairment is due to congenital hypodysplasia.