Donor human leukocyte antigen specific antibodies predict development and define prognosis in transplant glomerulopathy (original) (raw)
Related papers
Transplantation, 2005
Background. Some studies have claimed that patients with immunoglobulin A (IgA) nephropathy have better graft survival than other renal graft recipients, whereas others have rejected this statement. We have addressed this paradox in the present study. Methods. In all, 1,207 patients with IgA nephropathy who received a primary cadaveric renal graft from 1990 to 2002 were identified in the Eurotransplant database. For comparison, we analyzed 7,935 patients with nonglomerular diseases. Death-censored graft survival was calculated using Kaplan Meier estimates and a multivariable Cox regression analysis was used for risk calculations. Results. Death-censored graft survival was superior in patients with IgA nephropathy in the first period after transplantation. After 3 years posttransplant, however, there was an accelerated decline in graft survival in recipients with IgA nephropathy. The fully adjusted risk of graft loss in the first year was increased by 40% in the control group compared to IgA nephropathy (hazard ratio [HR] 1.40, 95% CI 1.12-1.75), whereas the risk was significantly lower in the control group after the first year posttransplant (HR 0.75, 95% CI 0.63-0.88). Cold ischemia time, immunization and HLA-DR mismatch were risk factors for graft loss in the control group but not for IgA nephropathy, whereas HLA-AB mismatch was an independent risk factor, exclusively for the IgA nephropathy group. Conclusions. Recipients with IgA nephropathy have better 1-year graft survival, presumably due to favorable immunological behavior. This benefit was however abolished in the long-term by increased graft loss with time. Studies are needed to explain the difference in graft survival and the reason why different risk factors are involved in graft failure.
Transplantation, 2011
Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes. Methods. From September 2007 through September 2009, 244 consecutively transplanted kidney and kidney/pancreas recipients without pretransplant DSA were screened for de novo DSA at 1, 6, 12, and 24 months and when clinically indicated. Results. DSA was detected in 27% of all patients by protocol or indication screening. Patients with DSA (DSAϩ) were significantly more likely to have experienced acute rejection (AR) compared with no DSA (DSAϪ) (29% vs. 9.5%, PϽ0.001), and lower estimated 2-year graft survival (83% vs. 98%, PϽ0.001). Only 3 of 19 DSA (ϩ) patients with AR had DSA detected before the AR episode. When excluding patients with AR, 2-year graft survival was similar between DSA (ϩ) and DSA (Ϫ) patients (100% vs. 99%) as was estimated glomerular filtration rate. Patients with DSA detected by protocol screening had similar outcomes compared with DSA (Ϫ), whereas those with DSA detected by indication experienced significantly worse outcomes. Conclusions. Patients with de novo DSA experience worse graft outcomes due to previous/concurrent episodes of AR. A prospective DSA screening protocol failed to identify patients at risk for AR or poor short-term graft outcomes.
Human immunology, 2017
The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0.7%, 4.0% and 25.5% in NaS, NDSA and DSA patients, respectively (NaS vs. NDSA P=0.004; NaS vs. DSA P<0.001; NDSA vs. DSA P<0.001). Graft survival was lowest in DSA (78.7%), followed by NDSA (88.0%) and NaS (93.8%) recipients (NaS vs. NDSA P=0.015; NaS vs. DSA P<0.001; NDSA vs. DSA P=0.378). Multivariable competing risk analysis confirmed both NDSA (sHR=2.19; P=0.025) and DSA (sHR=2.87; P=0.012) as significant predictors of graft failure. The negative e...
Transplant Glomerulopathy: Clinical and Pathological Correlations
Transplantation Proceedings, 2009
Objective. Chronic transplant glomerulopathy (TG) is one of the leading causes of severe posttransplantation proteinuria and graft loss. Our current knowledge about risk factors for the development of TG, as well as factors that affect its dynamics and prognosis, is poor. We sought to describe the pathological and clinical risk factors and correlations of TG as well as parameters that influenced the survival of grafts with that pathology. Materials and Methods. We retrospectively reevaluated 86 kidney transplant cases with TG that have been recognized on the basis of an indication biopsy since 1997. All TG as well as all pre-TG (previous) biopsies were characterized for the presence of C4d deposits in the graft. Results. Younger recipient age and minimal immunosuppression due to drug withdrawal or suboptimal drug doses/blood levels within 3 to 6 months preceding the biopsy were associated with C4d deposition in peritubular capillaries (PTC; P ϭ .0053 and P ϭ .0365, respectively). Diffuse PTC-itis (P ϭ .029, RR [95% confidence interval] ϭ 3.349 [1.131-9.919]) and total interstitial inflammation score (P ϭ .015, RR [95% confidence interval] ϭ 9.662 [1.784-52.329]) were observed to show a negative impact on graft survival. C4d deposition in PTC and glomeruli, the level of pretransplantation sensitization, episodes of acute rejection, and C4d in previous (pre-TG) biopsies did not influence the survival of grafts with TG. Conclusions. Younger recipient age and minimal immunosuppression were associated with C4d positivity in grafts with TG. The survival of kidney grafts with TG was significantly affected by the magnitude of inflammation in the interstitium and PTC, but not by C4d positivity in PTC and glomeruli.
American Journal of Transplantation, 2011
reduced graft survival. Histologically, TG is typically seen >1 year posttransplantation. However, ultrastructural changes including glomerular endothelial swelling, subendothelial widening and early glomerular basement membrane duplication are associated with development of TG but appear much earlier. We examined the specificity of these changes for AMR, and whether these are inevitably associated with development of TG. Of 98 for cause renal allograft biopsies carried out within 3 months of transplantation with available serologic data, 17 showed C4d-positive AMR and 16 had histologic changes of AMR and donorspecific antibodies (DSA), but no C4d. All three ultrastructural changes were seen in 11 of 17 biopsies with C4d-positive AMR, 8 of 16 with histologic changes of AMR and DSA but no C4d, and 0 of 65 without histologic changes of AMR and/or DSA (p < 0.0001 for both of the former groups vs. the latter). Twenty patients with positive DSA (18 with histologic changes of AMR and 11 C4d-positive) had ≥1 follow-up biopsy; eight developed overt TG 3.5-30 months posttransplantation. Among the 18 patients with DSA and histologic changes of AMR, 11 C4d-positive and 7 C4d-negative, treatment for AMR after the early biopsy significantly reduced subsequent development of overt TG.
A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival
Nephrology Dialysis Transplantation
Background Pretransplant donor-specific anti-HLA antibodies (DSA) are associated with impaired kidney graft survival, while the clinical relevance of non-donor specific anti-HLA antibodies (nDSA) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSA and nDSA. Methods To eliminate donor and era-dependent factors, a post-hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995-2005 with available pretransplant serum samples. Anti-HLA antibodies were detected with a luminex single antigen bead assay. Results Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pretransplant DSA had a significantly lower 10-year death censored graft survival (55% vs. 82%, p=0.0001). Among 192 pairs with one recipient nDSA positive against either class I or II and the other without anti-HLA antibodies, graft survival did not significantly differ (74% vs. 77%, p=0.79). Only in patients with both nDSA class I and II there was a trend towards a lower graft survival (58%, p=0.06). Lastly, in a small group of 42 recipient pairs 10-year graft survival in recipients with DSA was 49% compared to 68% in recipients with nDSA (p=0.11). Conclusion This paired kidney analysis confirms that the presence of pretransplant DSA in deceased donor transplantations is a risk marker for graft loss, whereas nDSA in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSA against class I and II, nDSA may be a risk marker for graft loss in the long term.
İzmir tepecik eğitim hastanesi dergisi, 2021
Objective: Anti-human leukocyte antibodies (HLA) play an important role in graft survival, particularly in kidney transplantation. Preformed anti-HLA antibodies, especially donor specific antibodies can cause acute and chronic rejections. In this study, it was aimed to assess the effects of anti-HLA antibodies in kidney patients before transplant on graft function, failure, and patient survival. Methods: PRA (Panel Reactive Antibody) levels were monitored using bead based methods such as Luminex and flow cytometry. Post-transplant estimated glomerular filtration ratios (eGFR) among first, third, and fifth year patient survivals and graft failures were statistically analyzed. Results: In this study, it was observed that related transplants had low levels of PRAs, and their eGFRs were at normal reference range. The patients without acute rejection episode (ARE) had higher eGFR values than those with ARE. When five year-graft survival terms were evaluated, it was found that 65.6±9.8% and 86.5±3.2% graft survival terms were detected in anti-HLA Class I/II positive and negative patients, whereas 74.8±6.4% and 84.3 ±2.6% graft survival terms were observed in ARE positive and negative patients, respectively. eGFR value is a predictor of graft failure and patient survival. Our Cox regression analyses (HR=0.843, p=0.00) also supported this information. Conclusion: The study concluded that although the correlation between PRA positivity and graft survival were not significant, the shortest graft survival was observed in PRA positive patients in the whole cohort and ARE positive patients. The importance and requirement of pre-and post-transplant PRA tests continue.
Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study
HLA, 2017
The role of de novo donor-specific anti-HLA antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002-2014 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<0.001), with 54% of cases and 16% of controls (P<0.001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P<0.001) in patients with dnDSA (61% vs. 12%), in 53 (47%) patients that had at least 1 graft biopsy performed during follow-up. dnDSA was a significant risk factor (OR=6.06; P=0.003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor (HR=2.46; P=0.002) of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR=11.90; P=0.006) (HR=2.30; P=0.014) 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.