Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

Pre-transplant angiotensin II type 1 receptor antibodies: A risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT,Rab) are associated with a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and biopsy proven acute rejection (BPAR) during the first year post-transplant in adult renal transplant recipients (RTR), between 03/2009 and 08/2012. Pre-transplant sera were screened for AT1Rab (via enzyme linked immunosorbent assay) and donor specific anti-human leukocyte antigen antibodies (HLA-DSA, via Luminex). Three groups were analyzed: AT1Rab only (n=13); HLA-DSA only (n=8); and no AT1Rab or HLA-DSA (n=90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. RTR with AT1Rab had a lower median estimated glomerular filtration rate (eGFR=20 ml/min/1.73m2) when compared to RTR with no antibodies at 12 months. A significant difference in eGFR was observed since the first month post-transplant. Multivariate analysis showed four factors independently and significantly associated with eGFR at 12 months post-transplant: BPAR (beta -18.7, 95% CI -28.2 to -9.26, p<0.001), AT,Rab (beta -10.51, 95% CI -20.9 to -0.095 p=0.048), donor age (beta -0.42, 95% CI -0.75 to -0.103, p=0.010), and recipient age (3 -0.36, 95% CI -0.67 to -0.048, p= 0.024). In this study, AT1Rab in pre-transplant sera from RTR was an independent and significant risk factor contributing to a lower eGFR at 12 months posttransplant. This finding deserves to be confirmed in a larger RTR population.

Pre-nephrectomy angiotensin II type 1 receptor antibodies in living kidney donors: A concern?

Angiotensin II type 1 receptor (AT1R) autoantibodies (AT1Rab) have been associated with pre-eclampsia and malignant hypertension. Overactivity of the angiotensin-II/AT1R complex has also been implicated in cardiac, renal, and vascular remodeling, leading to mortality and morbidity from cardiovascular disease. Pre-donation prevalence and possible post-donation effects of AT1Rab in living kidney donors (LKD) are unknown. In this study, sera obtained the day before nephrectomy and kept frozen at -70 degrees C from 113 strictly normotensive and non-obese LKD were tested for AT1Rab by OneLambda detection assay. AT1Rab titers >or=17 international units were considered positive. Pre-donation renal function [estimated glomerular filtration rate (eGFR)] and blood pressure at 1 and 12 months post-donation were recorded in every patient. Ten of 113 (8.8%) LKD yielded a positive AT1Rab result. History of sensitization events was similar in both groups. There was no difference in renal function between LKD with positive and negative AT1Rab results, 1 (mean eGFR 73.8 versus 72.4 mL/min/1.73m2) and 12 months post-donation (mean eGFR 74.1 versus 74.5 mL/min/1.73m2). During follow-up, none of the LKD developed hypertension (defined as blood pressure >130/85), nor did they require antihypertensive drugs. AT1Rab are apparently indolent in healthy adults after short-term follow-up. Longer observation of all LKD will be necessary to draw final conclusions.