Membranous nephropathy in the UK Biobank

PLoS One. 2023 Apr 27;18(4):e0281795. doi: 10.1371/journal.pone.0281795. eCollection 2023.

Abstract

Background: Despite MN being one of the most common causes of nephrotic syndrome worldwide, its biological and environmental determinants are poorly understood in large-part due to it being a rare disease. Making use of the UK Biobank, a unique resource holding a clinical dataset and stored DNA, serum and urine for ~500,000 participants, this study aims to address this gap in understanding.

Methods: The primary outcome was putative MN as defined by ICD-10 codes occurring in the UK Biobank. Univariate relative risk regression modelling was used to assess the associations between the incidence of MN and related phenotypes with sociodemographic, environmental exposures, and previously described increased-risk SNPs.

Results: 502,507 patients were included in the study of whom 100 were found to have a putative diagnosis of MN; 36 at baseline and 64 during the follow-up. Prevalence at baseline and last follow-up were 72 and 199 cases/million respectively. At baseline, as expected, the majority of those previously diagnosed with MN had proteinuria, and there was already evidence of proteinuria in patients diagnosed within the first 5 years of follow-up. The highest incidence rate for MN in patients was seen in those homozygous for the high-risk alleles (9.9/100,000 person-years).

Conclusion: It is feasible to putatively identify patients with MN in the UK Biobank and cases are still accumulating. This study shows the chronicity of disease with proteinuria present years before diagnosis. Genetics plays an important role in disease pathogenesis, with the at-risk group providing a potential population for recall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Specimen Banks
  • Glomerulonephritis, Membranous* / diagnosis
  • Glomerulonephritis, Membranous* / epidemiology
  • Glomerulonephritis, Membranous* / genetics
  • Humans
  • Nephrotic Syndrome*
  • Proteinuria / pathology
  • United Kingdom / epidemiology

Grants and funding

This was an approved study (I.D. 1618) by UK Biobank (http:/ukbiobank.org). We acknowledge funding from Kidney Research UK (KRUK) for the Stoneygate Foundation Grant JFS_IN_003_20160914 MLD was supported by the KRESCENT post-doctoral fellowship from the Kidney Foundation of Canada There was no additional external funding received for this study’.