Desensitization Protocol in Recipients of Deceased Kidney Donor With Donor-Specific Antibody-Low Titers.

BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. METHODS: All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. RESULTS: The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. CONCLUSIONS: Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome.

Pretransplant donor-specific HLA antibodies detected by single antigen bead flow cytometry: risk factors and outcomes after kidney transplantation.

BACKGROUND: The clinical significance of pretransplant donor-specific antibodies (pre-Tx DSAs) detected by single antigen bead flow cytometry (SAB-FC) remains unclear. Our aim was to investigate the impact that pre-Tx DSAs detected by SAB-FC have on the early and late clinical outcomes. PATIENTS AND METHODS: We retrospectively tested stored frozen pre-Tx sera from 222 deceased-donor kidney transplants performed between November 1997 and November 2006. All patients had a negative complement-dependent cytotoxicity (CDC) cross-match with the donor. Median follow up was 5.1 years. RESULTS: Twenty-two (10%) patients had pre-Tx HLA antibodies detected by CDC. Pre-Tx HLA antibodies were detected using SAB-FC in the sera of 46 (20.7%) patients; 36 (16.2%) of them presented pre-Tx DSAs, 18 had class I antibodies, 9 class II, and 9 patients presented both classes. Mean pre-Tx DSA class I/II was 2360/1972 (MFI) mean fluorescence index in non CDC-sensitized patients. Pre-Tx DSAs were associated with female sex, retransplants, and pretransplant transfusions. Patients with Pre-Tx DSAs more than 1000 MFI and negative CDC screening presented a higher percentage of delayed graft function (61.1% versus 38.9%), more episodes of acute vascular rejection (33.3% versus 13.7%), and chronic rejection as the cause of allograft failure (22.2% versus 9.7%) compared with non-pre-Tx DSAs patients. Five-year allograft survival was significantly worse in patients with pre-Tx DSA (68.5% versus 82%, P = .006) and in patients with pre-Tx DSA class II more than 1000 MFI (43% versus 82%, P = .009). We didn't find differences in patient survival. DISCUSSION: Pre-Tx DSAs detected by SAB-FC were more frequent in female recipients, and they were associated with acute vascular and chronic rejection and a poorer graft outcome.

Donor-specific HLA antibodies: risk factors and outcomes after kidney transplantation.

BACKGROUND: Anti-human leukocyte antigen antibodies (HLA Abs) have been associated with reduced kidney allograft survival. Our aim was to analyze the prevalence and impact on allograft function of donor-specific HLA antibodies (DSA) among a cohort of kidney transplant recipients. PATIENTS AND METHODS: The 321 recipients had received deceased-donor kidneys followed for a median of 70 ± 43 months. We performed a cross-sectional analysis of the presence of HLA Abs with the use of Luminex technology. RESULTS: Fifty patients (15.6%) displayed HLA Abs after transplantation including 21 (6.7%) as de novo HLA Abs. Eight patients (2.5%) developed DSA, and 42 (13%) showed no DSA. We compared 3 groups of patients: with DSA, without DSA, and without HLA sensitization. The DSA patients were younger (P = .03) with a higher percentage of men (P = .00), and having received less frequent induction treatment with basiliximab or thymoglobulin (P = .02). Patients without DSA revealed a higher percentage of pretransplantation HLA sensitization (P = .00), more pretransplantation transfusions (P = .08), and more frequent retransplantations (P = .00). The incidence of acute rejections was higher for DSA patients (P = .02) than for the other 2 groups, behaving as an independent risk factor (relative risk, 4.7; 95% confidence interval, 1.1-18.8; P = .03). Graft survival at 5 years was lower among patients with compared to those without HLA Abs (P = .00). CONCLUSIONS: HLA donor-specific sensitization, an uncommon situation in our study, was associated with younger male recipients and less induction treatment. An acute rejection episode was an independent risk factor for the development of DSA; therefore, we think that monitoring of HLA Abs should be included in evaluation of the early postransplantation period.

Profilaxis de la transmisión vertical del VIH con zidovudina y lamivudina y neutropenia autoinmune / Prophylaxis against vertical human immunodeficiency virus with zidovudine and lamivudine and autoimmune neutropenia

La transmisión maternofetal es la principal causa de contagio por el virus de la inmunodeficiencia humana (VIH) en niños. La zidovudina (AZT) reduce el riesgo de transmisión vertical. La supresión de la medula ósea, incluyendo anemia y neutropenia, es el mayor efecto tóxico dosisdependiente limitante de la AZT. Excepcionalmente, se ha descrito neutropenia inducida por AZT en presencia de anticuerpos antineutrófilo en niños infectados por el VIH. En niños con infección VIH, se aprecia, con frecuencia, neutropenia como resultado de múltiples causas. La prevalencia de anticuerpos antineutrófilo es frecuente en estos pacientes, pero no parece que exista relación con la evolución a neutropenia. Hay pocos estudios sobre los efectos secundarios de la AZT en niños expuestos desde el periodo perinatal o sobre las posibles consecuencias de la exposición al VIH. Se presenta el caso de una recién nacida que recibe tratamiento para reducir la transmisión vertical por VIH y desarrolla una neutropenia en presencia de anticuerpos antineutrófilo. Esta rara complicación no ha sido descrita previamente en ningún niño expuesto de forma perinatal al VIH y tratado con zidovudina o lamivudina

Mother-to-infant transmission is the major means of infection by the human immunodeficiency virus (HIV) in children, Zidovudine (AZT) reduces the risk of vertical transmission, Bone marrow suppression, associated with disorders that include anemia and neutropenia, is the major dose-limiting toxic effect of AZT. On rare occasions, AZT-induced neutropenia in the presence of antineutrophil antibodies has been reported in HIVinfected children, Neutropenia is frequently detected in these patients and can have multiple causes. Antineutrophil antibodies are also prevalent, but their presence does not appear to correlate with the development of neutropenia. There are few studies on the secondary effects of AZT in children exposed during the perinatal period or on the possible consequences of exposure to HIV. We present the case of a newborn who, after treatment to reduce vertical HIV transmission, developed neutropenia in the presence of antineutrophil antibodies. To the best of our knowledge, this rare complication has not been reported previously in a child perinatally exposed to HIV and treated with zidovudine or lamivudine