Collaborative Brazilian Pediatric Renal Transplant Registry (CoBrazPed-RTx): A Report From 2004 to 2013.

BACKGROUND: The Collaborative Brazilian Pediatric Renal Transplant Registry started in 2004 as a multicenter initiative aiming to analyze, report, and share the results of pediatric kidney transplantation in Brazil. Data from all pediatric kidney transplants performed between January 2004 and December 2013 were recorded electronically and periodically updated. All patients under 18 years old from the participating centers were enrolled. Demographic data, etiology of chronic kidney disease, and patient and graft survival were analyzed. From a total of 2443 pediatric kidney transplants performed in Brazil during the study period, we report data from 1751 pediatric renal transplants performed in 13 centers enrolled in the collaborative study. Median age at transplantation was 12.4 years, and most of recipients were male (56%). The most common underlying renal etiologies were obstructive uropathy (31%) and glomerulopathy (26%). METHODS: According to donor source, 1155 (66%) of transplants were performed with deceased donors (DD). Initial immunosuppression consisted mainly of tacrolimus, mycophenolate, steroids, and induction therapy with anti-IL-2R antibodies. RESULTS: One-year graft survival (death-censored) was 93% and 90% (log rank test, P < .01), respectively, for living donor (LD) and DD. Graft losses (15%) were most frequently caused by vascular thrombosis, chronic allograft nephropathy, death with functioning kidney, acute rejection, and recurrent renal disease. Recipients of DD had 2.02 (95% confidence interval: 1.14-3.59) times the hazard of graft loss compared with those of LD (P = .015). Patient survival rates at 1 and 5 years were 98% and 97% for LD and 97% and 93% for DD, respectively. The mortality rate was 3.8%, mainly as the result of infection and cardiovascular disease. CONCLUSIONS: The results of this collaborative pediatric transplant study are comparable to international registries. Our effort has been able to maintain an exchange of information, both among the participating centers and with other international registries.

Gingival overgrowth in renal transplant recipients: a study concerning prevalence, severity, periodontal, and predisposing factors.

Gingival overgrowth (GO) is the main oral manifestation in transplant recipients who use calcineurin inhibitors. In the present study, factors for GO development were investigated in Brazilian renal transplant recipients who were prescribed cyclosporine (CsA) or tacrolimus (TAC). Demographic, pharmacological, clinical, and periodontal data were obtained from 83 patients, as well as HLA expression in 51 of them. The prevalence of GO was high (47%), but its severity was low according to periodontal indices. The prevalence of GO was greater among patients who used CsA (n = 49) than those receiving used TAC (n = 34) namely, 61% versus 26.5% (P = .003). Comparisons between patients with versus without GO were performed independent of the administered immunossupressant. The group with GO showed a greater degree of gingival inflammation index. HLA-A68 had greater expression among patients without GO (P = .04). The risk factors for GO occurrence were evaluated using a multivariate analysis that identified gingival inflammation and HLA-A24 expression as risk factors. Increased age and use of TAC were identified as protective factors. GO showed a high prevalence, yet a light intensity. Patients who were younger, men, or received CsA showed a greater occurrence of GO. The risk factors identified for GO development were the presence of gingival inflammation and HLA-A24 expression.

Absence of primary association between DM gene polymorphism and insulin-dependent diabetes mellitus or celiac disease.

The DMA and DMB genes encode class II-like heterodimetric molecules located in a specialized endocytic compartment, where they facilitate efficient loading of antigenic peptides on HLA class II molecules. Both genes are located within the MHC class II region and present a limited allelic polymorphism. Here we report the distribution of DM alleles in a group of 75 IDDM patients, 72 CD patients, and 162 random controls. We found a pronounced decreased frequency of DMA*0102 in both patient groups relative to controls. This difference was, however, mainly secondary to a strong negative linkage disequilibrium (LD) between this allele and the IDDM and CD-associated DRB1*03 allele. The DMB phenotype frequencies were similar in CD patients and controls. By contrast, we observed a decreased frequency of DMB*0101 and an increased frequency of DMB*0102 and DMB*0104 in IDDM patients. These differences disappeared when matching individuals for DRB1*03 or DRB1*04 alleles, which was in accordance with strong negative LD between DMB*0101 and DRB1*04 or DQB1*0302 alleles, and positive LD between DMB*0104 and DQB1*0201. Our data suggest that the apparent associations of IDDM or CD with given DM alleles are mostly secondary to primary associations with alleles at the DRB and DQB loci.

Linkage disequilibrium between HLA class II (DR, DQ, DP) and antigen processing (LMP, TAP, DM) genes of the major histocompatibility complex.

TAP, LMP and DM genes map within the major histocompatibility complex (MHC) class II region between the DQB1 and DPB1 loci, and are involved in the processing of peptides bound to HLA class I or class II molecules. In order to determine the various linkage disequilibria existing between these genes and HLA class II genes, we have analyzed TAP1, TAP2, LMP2, DMA, DMB, DRB1, DQA1, DQB1 and DPB1 polymorphisms in 162 unrelated healthy Caucasian individuals. Many positive or negative associations were observed between alleles at these loci, such as between DR/DQ and TAP2, DM or LMP, between DP and DMB, and between TAP2 and DM, TAP2 and LMP. Conversely, no linkage disequilibrium was detected between some closely related genes (DR/DQ and TAP1, TAP1 and TAP2, LMP2 and DM), in agreement with the existence of recombination hot spots in this region. Other weak linkage disequilibria are likely to exist in this region. These data allow to define some conserved MHC class II haplotypes including HLA class II and TAP, LMP and DM alleles. Furthermore, the knowledge of such linkage disequilibria is of outstanding importance in order to avoid misinterpretation of the data when studying MHC class II associations with autoimmune diseases.

Detection of antilineage specific leucocyte antibodies by a quantitative immunocytometry method in sera from candidates for renal allografts.

A sensitive and quantitative flow cytometry method for detecting antileucocyte antibodies was developed to study retrospectively samples from candidates using frozen donor cells and frozen recipient sera. This immunofluorescence method was used to compare levels of reactivities of serum antibodies before and after donor specific blood transfusion treatment and after renal transplantation. The results demonstrate that the flow cytometry crossmatch is a sensitive and accurate method which should be used prospectively before precluding transplantation in the presence of a positive B cell standard crossmatch. Antibodies detected by flow cytometry before transplantation could be responsible for an early acute rejection episode. Finally, combination of flow cytometry crossmatch and standard crossmatch assays might thus be useful before precluding transplantation in living related donors.