The Role of Human Leukocyte Antigen (HLA) Allele Patterns in the Incidence of End-Stage Renal Disease and HLA Antibody Production: Protocol for a Case-Control Study.

Background: The incidence of end-stage renal disease (ESRD) continues to increase globally, including in Indonesia, representing a significant public health burden. Genetic factors, particularly variations in human leukocyte antigen (HLA) alleles, have been suggested to contribute to ESRD susceptibility, either indirectly through their association with underlying immune-mediated diseases or directly through their involvement in immune regulation and renal injury pathways. Studies have shown varying results due to HLA polymorphisms, ethnicity, and environmental influences. HLA polymorphisms are suspected of influencing HLA antibody production, which in turn impacts kidney transplant outcomes. Although ethnicity is one of the factors that determine HLA allele variation in the population, research on HLA alleles has not been widely conducted in Indonesia. Objective: This study aims to analyze the role HLA alleles play in the occurrence of ESRD and their association with HLA antibody production. Methods: This observational case-control study incorporates both retrospective and prospective data collection at Dr Sardjito General Hospital, Yogyakarta. Retrospective HLA typing and HLA antibody data were obtained from the medical records of patients with ESRD and healthy controls between January 2020 and May 2026. Additional participants in both groups are being prospectively recruited between June and December 2026 according to predefined eligibility criteria. The case group will comprise participants aged 18 years or older with ESRD, complete HLA typing data for 8 loci, and available HLA antibody results, excluding those who have undergone kidney transplantation. The control group will comprise individuals aged 18 years or older with normal kidney function. HLA allele typing will be performed using a molecular method, namely, polymerase chain reaction sequence-specific oligonucleotide probes. HLA antibody testing will be performed using a solid-phase assay-based technology, specifically a Luminex single-antigen bead assay (DiaSorin), and both the HLA allele typing and HLA antibody testing will be analyzed using a LABScan3D analyzer (One Lambda Inc). The HLA antibody results will be subsequently categorized into positive and negative calculated panel reactive antibody (cPRA) statuses. Statistical analysis using odds ratio (OR) calculation will be performed to determine the association between specific HLA alleles and the occurrence of ESRD as well as HLA antibody production, with a 95% CI. Results: Participant recruitment and data collection began after approval of ethical considerations and are anticipated to be completed by December 2026. Dissemination of the study findings is planned for mid-2027. Conclusions: This study will evaluate the role of HLA class I and class II allele patterns in the development of ESRD and anti-HLA antibody production, as well as the influence of demographic characteristics, sensitization-related factors (including blood transfusion, pregnancy, and autoimmune disease), and clinical comorbidities on HLA antibody production and susceptibility to ESRD.