Evidence that HLA class II disparity is required for the induction of renal allograft enhancement by donor-specific blood transfusions in man.

We studied 46 living-related primary renal allograft recipients between June 1980 and Jan 1988 to determine if enhancement of allograft survival by donor specific transfusions requires a major histocompatibility complex mismatch between the blood/kidney donor and the recipient. Recipients were matched for a single HLA haplotype, but differed at various HLA loci on the unshared haplotype. DST (200 ml) was administered either 3 times at two-week intervals pretransplant (n = 17), or once 3-4 weeks pretransplant, together with oral azathioprine (1 mg/kg/day/28 days) (n = 29). Patients were followed for at least 1 year and all clinical rejection episodes were confirmed histologically. Enhanced graft survival by DST was defined as a rejection-free posttransplant course. Incompatibility for class II determinants on the unshared haplotype of donor had a beneficial effect. A significantly greater proportion of recipients had stable, rejection-free, allograft function if incompatible for the DR locus (80% vs. 44%, P = 0.012), for class II public determinants (100% vs. 58%, P = 0.013), or for at least one of the class II gene products (DR, DQ, class II public) (81% vs. 40%, P = 0.006). Graft loss occurred in 7 of 46 (15%); 6 of the 7 recipients were HLA class II-compatible with their blood/kidney donor. Mismatches for HLA class I private or public determinants and other factors known to affect graft outcome did not influence the results. We conclude that enhanced kidney allograft survival by DST may be predicated by factors within the MHC--specifically class II disparity. These observations also suggest that better HLA matching at the class II locus may account for the apparent "disappearance" of the transfusion effect in cadaver renal transplants in the cyclosporine era.

Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study.

Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.