HLA Class I and II Associations with Renal Function and Associated Conditions in an Aging Population

  • Marcus Lowe

Student thesis: Phd


Introduction Kidney dysfunction is a highly significant disease, both in the United Kingdom and globally. Human leukocyte antigens (HLA) are thought to be associated with kidney function; this study aims to collate all previously reported associations between HLA and renal function, and to identify novel associations (and replicate previous findings) by analysing a cohort of subjects recruited in the UK. Secondary analysis investigated whether there is a link between Covid-19 and either HLA or renal function. Methods A systematic review was performed to identify all studies that had looked for associations between HLA and renal function. Additionally, regression analyses were performed to test for HLA associations with renal function in a cohort of around 500,000 UK Biobank subjects aged 39-73. Seven different ethnic groups and 362 HLA types were included. The primary outcome was estimated glomerular filtration rate (eGFR), with clinical outcomes used in secondary analyses. Finally, regression analysis was performed to test for associations between Covid-19, HLA, and renal function in cohorts of up to 6,000 Covid-19 positive subjects aged 50-86. Results 35 papers investigating the link between HLA and renal function were identified, with over 100 HLA types and haplotypes reported to be associated with kidney function. These findings were collated and published. This study revealed 33 HLA types that were linked to kidney function in white British subjects (11 hazardous and 22 beneficial). Studies of other ethnicities revealed nine significant associations, e.g., four alleles were linked to decreased function in Black African subjects. The findings relating to Covid-19 were limited. Previously reported associations were replicated (e.g., increased age and male sex were linked to increased mortality), but there were no associations found between Covid-19 and either HLA or renal function. Discussion This thesis provides a list of all previously reported associations between HLA and renal function, and also presents a number of novel associations. Many of the associated alleles are commonly inherited together as haplotypes: HLA-A*01:01, B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 has 9.5% frequency in England and each allele was associated with decreased renal function in white British subjects. This may have clinical applications and could affect the UK’s organ allocation algorithm.
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorAntony Payton (Supervisor), Kay Poulton (Supervisor), William Ollier (Supervisor), Islay Gemmell (Supervisor) & Arpana Verma (Supervisor)


  • kidney transplantation
  • NHS
  • COVID-19
  • genetic predisposition to disease
  • HLA
  • renal replacement therapy
  • polymorphism, single nucleotide
  • histocompatibility antigens
  • glomerular filtration rate
  • systematic review
  • renal insufficiency
  • kidney failure, chronic
  • HLA antigens
  • genome-wide association study
  • imputation

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