Longitudinal Dynamics of Angiotensin II Type 1 Receptor Antibodies Around Kidney Transplantation and Their Impact on Clinical Outcomes
Conditions: Kidney Transplantation, Graft Survival, Angiotensin II Type 1 Receptor Antibody
Sponsor: Seoul National University Hospital

Cover Page  
 
Official Title: Longitudinal Dynamics of Angiotensin II Type 1 Receptor Antibodies and Their 
Impact on Kidney Transplantation Outcomes 
 
NCT Number: pending 
 
Document Date: 2024-12-09 
 
 

Study Protocol  
 
1. Study Objectives 
The primary objective of this study was to evaluate the impact of longitudinal changes in 
AT1R-Ab levels during the first year after transplantation on clinical outcomes in kidney 
transplant recipients. The initial analysis focused on characterizing the trajectory of AT1R-Ab 
concentrations over time. 
Secondary outcomes included the incidence of de novo donor-specific antibody (DSA) 
formation and changes in renal function by AT1R-Ab group. Renal function was evaluated 
using serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) at 2 weeks, 3 
months, and 1-year post-transplant. 
 
2. Study Design 
Design: Retrospective cohort study. 
Study Population: Kidney transplant recipients between 2016 and 2022 at Seoul National 
University Hospital 
 
3. Inclusion Criteria: 
Eligible patients were those who had serum samples collected at pre-transplant and at 2 weeks, 
3 months, and 1-year post-transplant, with a minimum follow-up of 1 year 
 

4. Exclusion Criteria: 
Exclusion criteria were simultaneous multi-organ transplantation and age younger than 18 
years. 
 
 
 

Statistical Analysis Plan  
Group comparisons were performed at four time points: pre-transplant, and at 2 weeks, 3 
months, and 1-year post-transplant. Continuous variables were summarized as means with 
standard deviations and compared using one-way analysis of variance (ANOVA) or Kruskal–
Wallis tests, as appropriate. Categorical variables were expressed as frequencies and 
percentages, and differences between groups were assessed using chi-square tests or Fisher’s 
exact tests. 
To visualize longitudinal changes in AT1R-Ab group classification, Sankey diagrams were 
constructed to illustrate dynamic transitions between antibody groups over time. 
The associations between AT1R-Ab groups and post-transplant outcomes, including biopsy-
proven acute rejection (BPAR) and de novo donor-specific antibody (DSA) development, were 
analyzed over follow-up periods of 1 and 3 years using Marginal Structural Cox Models (Cox-
MSM). This approach accounted for time-varying confounding and exposure misclassification, 
and all available time-varying variables were incorporated into the model. 
Stabilized inverse probability weights were estimated based on the probability of remaining in 
a given antibody group at each time point. Covariates included age, sex, body mass index 
(BMI), pre- and postoperative angiotensin receptor blocker (ARB) use, pre- and postoperative 
hypertension, donor type, preemptive transplantation, kidney replacement therapy (KRT), 
donor–recipient relationship, compatibility, and desensitization. 
Although the HIGH group became very small by the 1-year time point, the IPW estimates did 
not diverge. To prevent potential instability due to small cell sizes, stabilized weights were 
calculated as the product of inverse probability of treatment weighting (IPTW) and inverse 
probability of censoring weighting (IPCW). 

For secondary outcomes, boxplots were generated to visualize the distribution of eGFR and 
SCr at 2 weeks, 3 months, and 1-year post-transplant by AT1R-Ab group. These graphical 
analyses illustrated variability, medians, and outliers within each group. Statistical 
comparisons were performed using parametric or nonparametric tests depending on data 
distribution. These analyses aimed to evaluate whether higher AT1R-Ab groups were 
associated with impaired kidney function as reflected by eGFR or SCr levels.