Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

The Association of Class I and II Human Leukocyte Antigen Serotypes With End-Stage Kidney Disease Due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease. American journal of kidney diseases : the official journal of the National Kidney Foundation Afolabi, H., Zhang, B. M., O'Shaughnessy, M., Chertow, G. M., Lafayette, R., Charu, V. 2023

Abstract

RATIONALE & OBJECTIVE: Membranoproliferative glomerulonephritis (MPGN), encompassing several distinct diseases, is a rare but significant cause of kidney failure in the US. Potential etiologies of MPGN are unclear, but prior studies have suggested dysregulation of the alternative complement pathway, and recently, autoimmunity as potential mechanisms driving MPGN pathogenesis. In this study, we examined HLA associations with end-stage kidney disease (ESKD) due to MPGN and Dense Deposit Disease (DDD) in a large racially and ethnically diverse US-based cohort.STUDY DESIGN: Case-control study.SETTING &PARTICIPANTS: Using USRDS and UNOS data, we identified 3424 patients with kidney failure due to MPGN and 263 due to DDD. We matched patients to kidney donor controls on designated race and ethnicity in a 1:15 ratio.EXPOSURES: 58 class I and II HLA serotypes.OUTCOMES: Case-control status.ANALYTICAL APPROACH: For each disease cohort, univariable and multivariable logistic regression analyses were used to investigate associations between the disease and 58 HLA serotypes. In subgroup analyses, we investigated HLA associations in White and Black patients. We also studied anti-GBM nephritis as a positive-control outcome. We applied a Bonferroni correction to account for multiple comparisons.RESULTS: Eighteen serotypes were significantly associated with the odds of having MPGN in univariable analyses, with DR17 having the strongest association ([OR]: 1.55, 95% CI: 1.44-1.68; p-value 4.33e-28). No significant associations were found between any HLA serotype and DDD. Designated race-specific analyses showed comparable findings. We recapitulated known HLA associations in anti-GBM nephritis.LIMITATIONS: Reliance on HLA serotypes (rather than genotype), lack of biopsy-confirmed diagnoses.CONCLUSIONS: HLA-DR17 is associated with ESKD due to MPGN in a racially and ethnically diverse cohort. The strength of association was similar in White and Black patients, suggesting a role in the pathogenesis of MPGN. No HLA associations were observed in patients with DDD.

View details for DOI 10.1053/j.ajkd.2023.06.005

View details for PubMedID 37739026