Impact of early lymph node procurement to facilitate histocompatibility testing on long-term cadaveric kidney graft survival.

BACKGROUND: Prolonged cold ischemia time (CIT) is a clinically important causes of delayed graft function (DGF) after kidney transplantation. As DGF has been previously shown to have a deleterious influence on long-term graft survival, in the present study we analyzed the impact of early lymph node (LN) procurement on CIT, HLA mismatches, and long-term kidney graft outcome. MATERIALS AND METHODS: We evaluated 394 consecutive cadaveric procedures performed from 2001 to 2006, including 289 recipients, in whom LN were obtained before kidney procurement seeking to shorten the total time for HLA typing and crossmatch procedures. RESULTS: During 58±6 months, 24 patients died (918 [8.3%] in the early and 6 [5.7%] in late procurement group, P=ns) and 52 lost their kidney grafts (31 [10.7%] vs 21 [20%]; P=.025). Early procurement of LN performed in 73.4% of all kidney graft recipients shortened CIT by almost 7 hours (22.9 vs 16.1 hours; P<.001), with a nonsignificantly lower incidence of DGF (32.2% vs 41.0%; P=.13). However, a Cox proportional hazards regression model revealed that early procurement reduced the risk of death-censored kidney graft loss by roughly 40% (log-rank, P=.013). CONCLUSION: Early LN procurement in significantly shorten CIT and subsequently reduced the risk of long-term kidney graft loss.

-174G/C interleukin-6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5-year follow-up period.

The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one-centre study was to analyse the association between tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and transforming growth factor-ß1 (TGF-ß1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5-year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-α (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C), IFN-γ (+874T/A) and TGF-ß1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-ß1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.

The impact of H-Y mismatches on results of HLA-matched unrelated allogeneic hematopoietic stem cell transplantation.

We searched for immunogenic mismatches of H-Y minor histocompatibility antigens among unrelated HLA-matched donor-recipient pairs and for their association with transplant outcomes. We included 92 patients who were treated with 10/10 HLA allele-matched, unrelated allogeneic hematopoietic stem cell transplantation (alloHSCT). H-Y genotyping was performed in the Regional Blood Center with use of the Dynal Minor Histocompatibility Antigen Typing Kit. H-Y mismatches in the graft-versus-host direction of female donor to male recipient decreased the relapse rate (6% vs 23%; P=.046) and tended to improve disease-free survival (79% vs 44%; P=.067), but it also increased the incidence of chronic graft-versus-host disease (66% vs 38%; P=.02). Thus it influenced the results of alloHSCT from HLA-matched unrelated donors. The results of this study may help to explain the impact of gender differences between donor and recipient in alloHSCT.

Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT.

We determined the alleles of 11 mHAs and investigated the association of immunogenic mHA mismatches between a donor and a recipient with a course of allogeneic hematopoietic SCT (allo-HSCT) from 10/10 alleles HLA-matched unrelated donors in 92 recipients after myeloablative conditioning between 2004 and 2006. The frequency analysis of mHA alleles, genotypes and phenotypes accompanied by appropriate restriction HLA Ags allowed for an estimation of the probability of immunogenic mismatches, which was the highest for HA-1, HA-8 and HY. GVH-directed disparity of mHAs with broad tissue distribution, especially of the sex-related HY Ag, influenced the results of allo-HSCT from HLA-matched unrelated donors by not only increasing the probability of chronic GVHD (cGVHD) but also by decreasing the relapse rate.

Limbal stem cells transplantation in the reconstruction of the ocular surface: 6 years experience.

PURPOSE: To analyze the graft survival rate and stability of the corneal surface in patients who underwent limbal stem cell transplantation. Three surgical techniques were performed based on the origin of the ocular surface lesion: conjunctival limbal autograft (CLAU), living-related conjunctival limbal autograft (lr-CLAL), and keratolimbal allograft (KLAL) transplantations. METHODS: Nonrandomized consecutive comparative case series study. Eighty-four patients (90 eyes; 31 women and 53 men; age range: 11-78 years) were included in the study. Mean follow-up was 31.2 months (range: 6-72 months). Patients were divided into three groups: CLAU, lr-CLAL, and KLAL, comprising 21, 26, and 43 eyes, respectively. Graft survival rate and clinical success of the stem cell transplantation was confirmed by impression cytology. The Kaplan Meier survival curve and generalized Peto tests were used for the analyses. RESULTS: Graft survival rate and the regularity of the corneal surface differed significantly between the allo- and autografts. The 3-year and 6-year graft survival rates were 76.1% and 61.9%, respectively, for the autologous transplantation group, and 59.4% and 46.3%, respectively, for the allogeneic transplantation group. Corneal surface restoration correlated with positive staining for corneal epithelial cells in impression cytology. CONCLUSIONS: Significantly better long-term outcomes were achieved with autotransplantation of the limbus compared with allogeneic limbal grafts from living-related and cadaveric donors.

Early donor lymph node procurement and local HLA typing reduce cold ischemia time and risk of acute tubular necrosis in cadaveric kidney transplantation.

Prolonged cold ischemia time (CIT) is one of the most common causes of acute tubular necrosis (ATN) with consequent delayed graft function after kidney transplantation. The aim of the study was to analyze the impact of early donor lymph nodes (LN) procurement in combination with local or central HLA typing on CIT, on donor-recipient HLA mismatches, and on the early results of grafts. Two hundred six cadaveric procedures were performed from 2001 to 2004 including 86 cases out of 119 recipients who were matched locally and 60 cases out of 87 recipients who were matched centrally, wherein LN were obtained before kidney harvest. CIT was significantly shorter when LN were obtained before kidney harvesting both in local (13.6 vs 20.6 hours) and central (20.1 vs 27.7 hours) matching (both P < .001). ATN frequency was significantly lower in patients with LN obtained earlier (27.9%) when matched locally versus (35.0%) when matched centrally. Kidney graft function estimated at 12 months was similar in both groups. CIT longer than 19.5 hours predicted ATN occurrence with 57.7% sensitivity and 66.4% specificity. Local matching resulted in shortening CIT compared to central matching (15.5 vs 22.4 hours); however, the mismatch in HLA class I and HLA class II were significantly worse (HLA A + B 2.76 vs 2.45, HLA DR 1.21 vs 0.82). These discrepancies did not significantly influence the frequency of ATN (36.1% vs 40.0%) or the kidney graft function at 12 months.