Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d-). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group.

Immunoglobulin G subclass analysis of HLA donor specific antibodies in heart and renal transplant recipients.

Immunoglobulin G (IgG) subclasses IgG1 (G1) and lgG3 (G3) can induce complement dependent cytotoxicity (CDC) and bind to Fc receptors (FcR), which induces phagocytosis and antibody dependent cellular cytotoxicity. In contrast, IgG2 has low CDC activity, lgG4 (G4) has no CDC activity, and neither binds high affinity FcR. Seven transplant recipients were analyzed for G1- G4 human leukocyte antigen (HLA) donor-specific antibodies (DSAs); six had active rejection and one had stable function.

Reduction of HLA class I expression by ribonucleic acid interference mitigates allogenicity of human primary and Immortalized cells.

Unmatched human leukocyte antigens (HLA) expressed by allogeneic donor cells are the major target for immunological rejection. In order to reduce the immunogenicity of allograft cells, we have developed lentiviral vectors for delivery of short hairpin ribonucleic acid (shRNA) against Class I HLA. This approach was evaluated in both an established human embryonic kidney cell line and primary human CD34+ hematopoietic stem/progenitor cells.

Effects of mycophenolic acid on highly sensitized patients awaiting kidney transplant.

Background: 10-30% of dialysis population awaiting renal transplantation is sensitized. Mycophenolic acid (MPA) has been shown to reduce panel reactive antibody (PRA) formation in kidney transplant recipients. Our aim was to investigate whether MPA could effectively reduce anti-HLA antibody levels and allow successful transplantation.

Impact of hepatitis C infection on outcomes after heart transplantation.

Background: Prevalence of hepatitis C infection (HCV) among heart transplant (OHT) recipients ranges from 7% to 18%. Despite the paucity of data regarding the outcomes of heart transplant recipients who are HCV positive before transplant, many transplant centers are declining to perform OHT in HCV-seropositive patients.

Methods: We assessed the clinical outcome of HCV-seropositive compared with HCV-seronegative heart transplant recipients using the Organ Procurement and Transplant Network/the United Network for Organ Sharing database.

Long-range linkage on chromosome 6p of VEGF, FKBP5, HLA and TNF alleles associated with transplant rejection.

Polymorphisms in several genes on the short arm of chromosome 6 (6p), among them, VEGF, FKBP5, HLA-DR and TNF-alpha, have been associated with inflammation and transplant outcome, such as acute rejection. Independent segregation of these genes is unproven, so we investigated linkage between distant genes on 6p and the putative existence of evolutionarily conserved long-range 6p haplotypes. SNPs studied were VEGF-2578*C/A (rs69947), VEGF-1154*G/A (rs1570360) TNF-alpha-308*G/A (rs1800629) and FKBP5*C/T (rs1360780) in 206 random and 80 selected HLA-DR52 positive individuals.

ASSOCIATION BETWEEN DE NOVO DONOR SPECIFIC HLA ANTIBODY, C4D STAINING IN RENAL GRAFT BIOPSY AND GRAFT OUTCOME: A SINGLE CENTER EXPERIENCE.

In 69 renal transplant recipients (RTR), all had a functioning graft (SCr < 2.0) at one year. After one year, transplant dysfunction was observed and these 69 RTR were biopsied, tested for C4d deposition and donor specific antibodies (DSA).

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

Background: There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT).

Methods: Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT.

Risk factors for short- and long-term survival of primary cadaveric renal allografts in pediatric recipients: a UNOS analysis.

Background: Pediatric kidney graft survival rates have improved in the United States. This study evaluates early and late risk factors for cadaveric graft loss in pediatric recipients.

Methods: From January 1994 to December 2002, 2,597 primary cadaveric kidney-alone transplants (donor age 5-45 years, recipient age 2-20 years) were reported to the United Network for Organ Sharing (UNOS).