scholarly journals Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

2021 ◽  
Vol 16 (2) ◽  
pp. 275-283
Author(s):  
James H. Lan ◽  
Matthew Kadatz ◽  
Doris T. Chang ◽  
Jagbir Gill ◽  
Howard M. Gebel ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Specific Antibody ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Transplant Recipients ◽  
Allograft Survival ◽  
Specific Antibodies ◽  
Panel Reactive Antibody ◽  
Donor Specific Antibodies ◽  
Reactive Antibody

Background and objectivesPanel reactive antibody informs the likelihood of finding an HLA-compatible donor for transplant candidates, but has historically been associated with acute rejection and allograft survival because testing methods could not exclude the presence of concomitant donor-specific antibodies. Despite new methods to exclude donor-specific antibodies, panel reactive antibody continues to be used to determine the choice of induction and maintenance immunosuppression. The study objective was to determine the clinical relevance of panel reactive antibody in the absence of donor-specific antibodies.Design, setting, participants, & measurementsRetrospective observational study of kidney allograft survival among 4058 zero HLA-A–, B-, DR-, and DQB1-mismatched transplant recipients without antibodies to donor kidney antigens encoded by these HLA gene loci.ResultsAmong 4058 first and repeat transplant recipients, patients with calculated panel reactive antibody (cPRA) 1%–97% were not at higher risk of transplant failure, compared with patients with cPRA of 0% (death censored graft loss: hazard ratio, 1.07; 95% confidence interval, 0.82 to 1.41). Patients with cPRA ≥98% had a higher risk of graft loss from any cause including death (hazard ratio, 1.39; 95% confidence interval, 1.08 to 1.79) and death censored allograft failure (hazard ratio, 1.78; 95% confidence interval, 1.27 to 2.49). In stratified analyses, the higher risk of graft loss among patients with cPRA ≥98% was only observed among repeat, but not first, transplant recipients. In subgroup analysis, there was no association between cPRA and graft loss among living related transplant recipients.ConclusionsCalculated panel reactive antibody is poorly associated with post-transplant immune reactivity to the allograft in the absence of donor-specific antibody.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_25_CJN13640820_final.mp3

scholarly journals Underlying Causes and Risk Factors of Chronic Renal Allograft Dysfunction Among Renal Transplant Recipients

Acta Medica ◽  
2021 ◽  
pp. 1-10
Author(s):  
Göksel Güven ◽  
Şeref Rahmi Yılmaz ◽  
Tolga Yıldırım ◽  
Fazıl Tuncay Akı ◽  
Yunus Erdem
Keyword(s):  
Risk Factors ◽  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Chronic Allograft Dysfunction ◽  
Specific Antibodies ◽  
Panel Reactive Antibody ◽  
Allograft Dysfunction ◽  
Donor Specific Antibodies ◽  
Reactive Antibody

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients. Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively. Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p<0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p<0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p<0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002). Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.

scholarly journals Recurrence of IgA Nephropathy after Kidney Transplantation in Adults

2021 ◽  
Vol 16 (8) ◽  
pp. 1247-1255
Author(s):  
Audrey Uffing ◽  
Maria José Pérez-Saéz ◽  
Thomas Jouve ◽  
Mathilde Bugnazet ◽  
Paolo Malvezzi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Confidence Interval ◽  
Iga Nephropathy ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Content Type ◽  
Specific Antibodies ◽  
Donor Specific Antibodies ◽  
Recurrent Iga Nephropathy

Background and objectivesIn patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.Design, setting, participants, & measurementsWe performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 “The Post-Transplant Glomerular Disease” study centers in Europe, North America, and South America.ResultsOut of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.ConclusionsIn our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

scholarly journals Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival

2018 ◽  
Vol 29 (6) ◽  
pp. 1761-1770 ◽  
Author(s):  
Sarah B. See ◽  
Olivier Aubert ◽  
Alexandre Loupy ◽  
Yokarla Veras ◽  
Xavier Lebreton ◽  
...  
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Natural Antibodies ◽  
Kidney Graft ◽  
Pathogenic Potential ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Post Transplant

Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens.Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde.Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss.Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.

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