HLA Polymorphisms in End-Stage Renal Disease

Major histocompatibility complex genes encoding human leukocyte antigens (HLA) exhibit extensive polymorphism and play a pivotal role in immune recognition. In end-stage renal disease (ESRD), distinct HLA alleles and haplotypes have been associated with disease susceptibility, progression and post-transplant outcomes. Studies across diverse ethnic groups have identified both protective and risk alleles at HLA class I (A, B, C) and class II (DRB1, DQB1) loci. The interaction between HLA diversity and environmental factors, such as infections, autoimmune responses and cardiovascular co-morbidities, influences the onset and progression of renal failure. Understanding HLA polymorphisms in ESRD patients informs donor matching strategies, risk stratification prior to transplantation and potential immunomodulatory interventions. Global registries and biobank analyses have further revealed linkage disequilibrium patterns that guide haplotype-based prediction of renal function decline. Recent advances in high-throughput genotyping and imputation have enhanced resolution at four-digit allele levels, permitting refined association studies and meta-analyses. The translation of these findings into clinical practice holds promise for personalised approaches to monitoring, preventing and treating ESRD in populations worldwide.

Research from Nature Portfolio

Recent studies have leveraged large biobank datasets to impute high-resolution HLA types and assess their impact on renal outcomes. A landmark investigation in a White British cohort of over 400 000 individuals employed statistical imputation to evaluate associations between 362 HLA alleles and estimated glomerular filtration rate (eGFR). This analysis identified multiple class I and class II alleles correlating with both increased and decreased renal function, including a common haplotype (HLA-A*01:01, B*08:01, C*07:01, DRB1*03:01, DQB1*02:01) linked to poorer eGFR and higher ESRD risk. The study underscored the influence of linkage disequilibrium in driving allele clusters and highlighted potential targets for early screening programmes and immunogenetic risk modelling.

HLA Polymorphisms in End-Stage Renal Disease publication trend

The graph below shows the total number of articles in hla polymorphisms in end-stage renal disease across all publications each year (not limited to Nature Index journals).

Technical terms

End-stage renal disease (ESRD): Final stage of chronic kidney disease characterised by irreversible loss of renal function requiring dialysis or transplantation.

Human leukocyte antigen (HLA): Proteins encoded by the major histocompatibility complex that present peptide antigens to T cells and exhibit high genetic variability.

Allele: A specific variant of a gene at a particular locus on a chromosome.

Polymorphism: The occurrence of two or more genetically determined variants in a population.

Haplotype: A group of alleles at adjacent loci on a chromosome that are inherited together.

Estimated glomerular filtration rate (eGFR): A calculated measure of kidney function based on serum biomarkers, age, sex and body size.

References

1. Associations between human leukocyte antigens and renal function. Scientific Reports (2021).
2. Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania. International Journal of Molecular Sciences (2023).
3. Association between human leukocyte antigen (HLA) and end-stage renal disease (ESRD): a meta-analysis. PeerJ (2023).
4. Revisiting the association between human leukocyte antigen and end-stage renal disease. PLOS ONE (2020).