Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Clinical relevance of anti-HLA donor-specific antibodies detected by Luminex assay in the development of rejection after renal transplantation.

BACKGROUND: The role of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA) detected by Luminex in the development of rejection is not fully understood. METHODS: A study including 369 patients who received transplants from deceased donors with a negative complement-dependent cytotoxicity crossmatch (XM) was performed. From the total of patients, 151 underwent a renal biopsy because of renal dysfunction, whereas the 218 remaining showed a stable renal function, and no rejection was assumed. Diagnosis and type of rejection was based in biopsy data. RESULTS: Patients with a positive virtual XMs showed more rejection episodes of any types when comparing with patients with negative virtual XMs (P<0.0001). Nevertheless, there were no significant differences between patients without anti-HLA antibodies and patients with anti-HLA no DSA. Allograft impairment was caused by a rejection episode in 84% (32/38) of patients with anti-HLA-DSA but only in 30% (34/113) of patients without anti-HLA-DSA. Regarding the type of rejection detected in the biopsy, all the patients with de novo (after transplantation) anti-HLA-DSA were diagnosed as antibody-mediated rejection (AMR) or AMR+T-cell-mediated rejection, whereas most of the patients without anti-HLA-DSA (68%) were diagnosed with T-cell-mediated rejection, and patients with preexistent anti-HLA-DSA showed a more homogeneous distribution of the different types of rejection. CONCLUSIONS: According to our results, patients with preformed or de novo anti-HLA-DSA showed the highest likelihood to suffer rejection episodes. Transplantation with preformed anti-HLA-DSA should be avoided, and an early detection of de novo HLA antibodies is important to treat patients before damage occurs in the graft.

Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation.

BACKGROUND: Clinical relevance of donor-specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch in pre-transplant serum samples from patients with a negative cytotoxicity-dependent complement crossmatch is controversial. The aim of this study was to analyse the influence of a pre-transplant positive virtual crossmatch in the outcome of kidney transplantation. METHODS: A total of 892 patients who received a graft from deceased donors after a negative cytotoxicity crossmatch were included. Presence of anti-human leucocyte antigen (HLA) antibodies was investigated using a Luminex screening assay and anti-HLA specificities were assigned performing a Luminex single antigen assay. RESULTS: Graft survival was significantly worse among patients with anti-HLA DSA compared to both patients with anti-HLA with no DSA (P = 0.001) and patients without HLA antibodies (P < 0.001) using a log-rank test. No graft survival differences between anti-HLA with no DSA and no HLA antibodies patient groups were observed (P = 0.595). Influence of both anti-Class I and anti-Class II DSA was detected (P < 0.0001 in both cases). When the fluorescence values were stratified in four groups, no significant differences in graft survival were observed among the groups with fluorescence levels >1500 (global P > 0.05). CONCLUSIONS: The presence of preformed HLA DSA in transplanted patients with a negative cytotoxicity crossmatch is associated with a lower allograft survival. The detection of anti-HLA with no DSA has no influence in the graft outcome. Finally, there were no demonstrable effects of mean fluorescence intensity (MFI) values >1500 on graft survival.

HLA-C and KIR genes in hepatitis C virus infection.

Natural killer (NK) cells are key components of the innate antiviral immune response. NK cell function is regulated by the interaction of major histocompatibility complex class I molecules with NK inhibitory receptors. The aim of this study was to investigate the role of the HLA-C/KIR pair in hepatitis C virus clearance in our population. A total of 196 hepatitis C virus-infected patients (65 resolved and 131 with persistent infection) were included in the study. Genotyping of HLA-C was carried out using polymerase chain reaction followed by a reverse sequence-specific oligonucleotide probe detection system. NK receptor-specific polymerase chain reaction typing of KIR2DL1, KIR2DL2, and KIR2DL3 was performed on the same patient group. Frequencies of the KIR2DL2 gene and the KIR2DL2/KIR2DL2 genotype were lower among patients with persistent infection (32.3% vs 45.4% among resolved, P = 0.01, OR = 0.57, 95% CI = 0.36-0.91; and 16.2% vs 32.3% among resolved, P = 0.02, OR = 0.41, 95% CI = 0.19-0.87). Nevertheless, the frequency of the KIR2DL3 gene was higher among patients with persistent infection (66.9% vs 54.6% among resolved P = 0.02, OR = 1.68, 95% CI = 1.07-2.65). Trends toward lower frequencies of the HLA-C2C2 genotype and NK-HLA interactions with strong and moderate affinity among the patients with persistent infection were also observed.