Angiotensin II type 1 receptor antibodies in childhood kidney transplantation

Abstract

Angiotensin II type 1 receptor antibodies (AT 1 RAb) have emerged as non-HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT 1 RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT 1 RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT 1 RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross-sectional study of 30 children (median age 14, range 3-19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20-40 yr, median time since tx 18 yr) transplanted between 1993-2006 and 1983-2002, respectively, was performed. Healthy controls were 51 healthy children (5-8 yr) and 199 healthy donors (median age 56.5 yr, range 42-83 yr). Plasma AT 1 RAb were analyzed by immunoassay. Median total AT 1 RAb IgG concentration was significantly higher in the pediatric-tx group as compared to the adult-tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric-tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult-tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT 1 RAb IgG (p = 0.0003). AT 1 RAb total IgG levels are significantly higher in a stable pediatric-tx cohort as compared to adult-tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies.

Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation

“…We and others have described that AT1R-Ab levels are higher in pediatric kidney transplant recipients when compared with adults. 33,35 Given AT1R-Ab and ETAR-Ab are highly correlated, 23 it is not surprising that we found a higher level to be more informative in our population. In an analysis of adult kidney transplant recipients with similar serial sampling, only 4% of blood samples were positive for ETAR-Ab (vs. 22% in our cohort) and only 56% of these samples were also positive for AT1R-Ab (vs. 96% in our cohort).…”

“…Our group 33 and others [34][35][36] recently reported a higher prevalence of AT1R-Ab in pediatric versus adult kidney transplant recipients, highlighting potentially important differences between these 2 populations with respect to the development of non-HLA antibodies. In particular, pediatric kidney transplant patients appear to have a higher rate of de novo AT1R-Ab formation.…”

Impact and production of Non‐HLA‐specific antibodies in solid organ transplantation

“…Levels of AT 1 R antibodies have been found associated with the age of the patient. The median AT 1 R antibody level has already reached the saturated level of the assay in stable paediatric transplant patients, which is significantly higher than in the adult transplant group and the control non‐transplant group (Bjerre et al., 2016). This result suggests that the interpretation of AT 1 R test results may need to consider all confounding factors.…”

“…The presence of these non‐HLA antibodies does not always cause graft dysfunction. It has been reported that AT 1 R antibodies caused acute rejection in two paediatric kidney transplant cases, while some paediatric kidney transplant recipients who had high levels of AT 1 R antibodies had normal graft function (Pearl et al., 2015) (Bjerre et al., 2016). The precise role of these non‐HLA antibodies in graft rejection warrants further study.…”

Imaging in pediatric renal transplantation

“…Angiography and embolization will be performed if intrarenal lesions are clinically significant. Hypertension, a common complication after rTX, occurs in 30%–50% of all kidney transplant recipients depending on the method of blood pressure measurement, definition, and normative data used . Up to 7% have uncontrolled hypertension with SBP greater than 95th percentile despite being on antihypertensive medications due to RAS.…”