JMIR Publications

ABSTRACT

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. Various 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. Research on HLA alleles have not been widely conducted in Indonesia, although ethnicity is one of the factors that determine HLA allele variation in the population.

Objective:

This study aims to analyze the role of HLA alleles in the occurrence of ESRD and their association with HLA antibody production.

Methods:

This is a case-control study. Study subjects consisted of ESRD patients who will undergo HLA typing and HLA antibody testing at Dr. Sardjito General Hospital, Yogyakarta as the case group and healthy controls. The inclusion criteria for the case group are ESRD patients aged ≥18 years with complete HLA typing data from eight loci and available HLA antibody results. The control group consisted of individuals aged ≥18 years with normal kidney function. HLA allele typing was performed using a molecular method, namely Polymerase Chain Reaction Sequence-Specific Oligonucleotide Probes (PCR-SSO). HLA antibody testing was performed using a solid-phase assay-based technology, specifically the Luminex Single-Antigen Bead (SAB) assay, and both examinations were analyzed using the LabScan 3D system. The HLA antibody results were subsequently categorized into positive and negative Calculated Panel Reactive Antibody (cPRA) status. Statistical analysis using Odds Ratio (OR) calculation was performed to determine the association between specific HLA alleles and the occurrence of ESRD as well as HLA antibody production, with a 95% confidence interval.

Results:

Participant recruitment and data collection began in June 2026 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.