Compatibility and Kidney Transplantation: The Way to Go

Long lasting debates in the past questioned the relevance of any sort of compatibility in post mortal kidney transplantation. It is for no say that fully compatible transplants have the highest chances for a long patient and graft survival. In the present report the use of HLA-DR as a representative of the Major Histocompatibility Complex class II genes in the allocation of organs is discussed. The major arguments are the easiness to offer to patients a compatible graft in a relatively short waiting time, an increase in graft survival, the less sensitization during the transplantation period, and the lower waiting time for a retransplant. Even if the number of organ donors remains the same a lowering of the mean waiting time is expected because of the longer period of graft survival

A snapshot of the Mamu-B genes and their allelic repertoire in rhesus macaques of Chinese origin

The major histocompatibility complex class I gene repertoire was investigated in a large panel of rhesus macaques of Chinese origin. As observed in Indian animals, subjects of Chinese derivation display Mamu-B gene copy number variation, and the sum of expressed genes varies among haplotypes. In addition, these genes display differential transcription levels. The majority of the Mamu-B alleles discovered during this investigation appear to be unique for the population studied. Only one particular Mamu-B haplotype is shared between Indian and Chinese animals, and it must have been present in the progenitor stock. Hence, the data highlight the fact that most allelic polymorphism, and most of the Mamu-B haplotypes themselves, are of relatively recent origin and were most likely generated after the separation of the Indian and Chinese rhesus macaque populations

Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins

Abstract The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33 % of either HTK-(n = 105) or UW-(n = 99) preserved kidneys ( P = NS), and in 29% of the HTK-(a = 85) and in 43 O/O of the EC-(a = 119) preserved kidneys ( P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73 YO, compared to 68 YO for UW-preserved kidneys in the UW-HTK study ( P = NS); while the 3-year graft survival of HTK preserved kidneys was 70 % compared to 67 % for EC-preserved kidneys in the EC-HTK study ( P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided

Compound Evolutionary History of the Rhesus Macaque Mhc Class I B Region Revealed by Microsatellite Analysis and Localization of Retroviral Sequences

In humans, the single polymorphic B locus of the major histocompatibility complex is linked to the microsatellite MIB. In rhesus macaques, however, haplotypes are characterized by the presence of unique combinations of multiple B genes, which may display different levels of polymorphism. The aim of the study was to shed light on the evolutionary history of this highly complex region. First, the robustness of the microsatellite MIB-linked to almost half of the B genes in rhesus macaques (Mamu-B)–for accurate B haplotyping was studied. Based on the physical map of an established haplotype comprising 7 MIB loci, each located next to a certain Mamu-B gene, two MIB loci, MIB1 and MIB6, were investigated in a panel of MHC homozygous monkeys. MIB1 revealed a complex genotyping pattern, whereas MIB6 analysis resulted in the detection of one or no amplicon. Both patterns are specific for a given B haplotype, show Mendelian segregation, and even allow a more precise haplotype definition than do traditional typing methods. Second, a search was performed for retroelements that may have played a role in duplication processes as observed in the macaque B region. This resulted in the description of two types of duplicons. One basic unit comprises an expressed Mamu-B gene, adjacent to an HERV16 copy closely linked to MIB. The second type of duplicon comprises a Mamu-B (pseudo)gene, linked to a truncated HERV16 structure lacking its MIB segment. Such truncation seems to coincide with the loss of B gene transcription. Subsequent to the duplication processes, recombination between MIB and Mamu-B loci appears to have occurred, resulting in a hyperplastic B region. Thus, analysis of MIB in addition to B loci allows deciphering of the compound evolutionary history of the class I B region in Old World monkeys

Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study

ObjectiveTo determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT).Study DesignNeurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness.ResultsA total of 291 children were evaluated at a median age of 8.2 years (range, 2–17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7–92.7).ConclusionIncidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome