Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study.

The role of de novo donor-specific anti-human leukocyte antigen (anti-HLA) antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002 and 2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy. All patients had at least one serum collected 1 year before failure (in cases) or end of follow-up (in controls). Cases and controls were very well-matched in several baseline characteristics. Post-transplant anti-HLA antibodies were found in 84% of cases and only 36% of controls (P < .001), with 54% of cases and 16% of controls (P < .001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P < .001) in patients with dnDSA (61% vs 12%), in 53 (47%) patients that had at least one graft biopsy performed during follow-up. dnDSA was a significant risk factor (odds ratio [OR] = 6.06; P = .003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor [hazard ratio (HR) = 2.46; P = .002] of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR = 11.90; P = .006) (HR = 2.30; P = .014) was significantly associated with graft failure. Post-transplant dnDSA was clearly associated with graft loss, particularly if against HLA class II antigens. dnDSA detection should be a tool for post-transplant monitoring of kidney graft recipients, allowing for the identification of those with a higher risk of graft failure.

Low transplantability of 0 blood group and highly sensitized candidates in the Portuguese kidney allocation algorithm: quantifying an old problem in search of new solutions.

The impact of patient's biological differences in waiting time for kidney transplantation is well known and has been a subject of extensive debate and struggle in transplantation community. Our purpose was to evaluate patient's access to kidney transplantation in Portugal, regarding their degree of allosensitization and blood type. A retrospective cohort study including 1020 candidates for kidney transplantation between 01 January 2010 and 31 December 2011 in transplant unit Centro Hospitalar do Porto was performed. The deceased donor organ offer by blood type decreased with the calculated panel reactive antibody (cPRA) increase for A and B blood groups candidates, while in 0 blood group candidates, a significant reduction in organ offer was only observable in hypersensitized (HS) ones. As a consequence, the median waiting time was also significantly higher in 0 blood group patients, when compared to the remaining groups. However, waiting time increased extensively with cPRA regardless blood type, especially HS patients with increases of 368%, 632%, 486%, and 140% for blood groups A, B, AB, and 0, respectively, when compared to each blood group global median waiting time. Our study shows that important measures need to be undertaken in order to mitigate the huge disadvantage that HS and 0 blood type patients naturally have.

Effect of Different Sensitization Events on HLA Alloimmunization in Kidney Transplantation Candidates.

BACKGROUND: HLA alloimmunization is caused by sensitization events (SEs), such as transfusion, pregnancy, or previous organ transplantation, and the effects of particular SEs have not been thoroughly studied. Our aim was to evaluate how each SE affected HLA alloimmunization by considering Luminex assays. METHODS: Sera from 722 kidney transplantation candidates were screened per protocol by means of Luminex assays to determine the presence of anti-HLA class I/II antibodies; positive sera underwent single-antigen assay to determine the presence of specific antibodies against HLA A, B, C, DR, DQ, DP loci (positivity if median fluorescence intensity values were >1,000). The effect of each SE was analyzed considering only patients exposed to 1 kind of sensitization. RESULTS: In the 453 candidates with ≥1 SE, anti-HLA class I positivity rates were significantly higher in patients with previous transfusion (18.9%; P = .014), pregnancy (38.3%; P < .001) or transplant (75%; P < .001) compared with those with no SE (similar results for class II). The strength (median fluorescence intensity) of specific antibodies was significantly higher in patients with previous transplantation than in those with previous transfusion for HLA-A (8,017 vs 2,302; P = .02), HLA-B (7,765 vs 2,901; P = .018), and HLA-DR (9,835 vs 2,060; P = .003). Other anti-HLA antibody strengths were similar between patients with previous pregnancy or transplantation. CONCLUSIONS: Presence of any SE analyzed was associated with a higher prevalence of anti-HLA antibodies for class I ± II compared with nonsensitized patients. Transplantation had the strongest immunization effect on both classes, followed by pregnancy and then transfusion.

Kidney transplantation across a positive crossmatch: a single-center experience.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease, with improved mortality and quality of life compared with dialysis. Desensitization protocols have allowed kidney transplantation of highly sensitized patients, who have a lower probability to receive a matching kidney from a deceased or living donor. The aim of this work was to analyze the post-transplantation period of highly HLA-sensitized patients with positive flow cytometry crossmatch against donor cells. METHODS: Following an observational, retrospective design, we investigated 16 highly sensitized patients who underwent kidney or kidney-pancreas transplantation, assessing the impact of desensitization protocols and investigating treatment-related complications, graft function, antibody-mediated rejection (AMR) rate, and graft and patient survivals. RESULTS: We studied 16 patients with positive flow cytometry crossmatch, who were divided into 2 groups based on whether they were submitted to a desensitization protocol or not. Patients who were desensitized underwent transplantation in later years, had higher immunologic risk (panel reactive antibody peak 62% vs 33%; P = .038), higher percentage of 2nd kidney transplant (75% vs 25%; P = .066), and higher percentage of donor-specific anti-HLA antibodies identified (P = .028). A majority of patients were desensitized with high-dose intravenous immunoglobulin and plasmapheresis, and 5 patients received rituximab. Acute AMR rate was of 38%, and rituximab was associated with fewer episodes of AMR. Only 1 patient had graft failure, due to chronic humoral rejection, and the remaining maintained good graft function (mean serum creatinine value of 1.33 mg/dL). No patient died and few complications related to immunossupression were observed. CONCLUSIONS: Desensitization protocols were safe and allowed kidney transplantation in highly sensitized patients that probably would never undergo transplantation and gave the opportunity of living-donor transplant to patients with anti-HLA antibodies against the donor.