Genetics of longitudinal kidney function in children and adults with systemic lupus erythematosus.
Rheumatology (Oxford)
; 62(11): 3749-3756, 2023 11 02.
Article
em En
| MEDLINE
| ID: mdl-36916720
ABSTRACT
OBJECTIVES:
Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE.METHODS:
Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags.RESULTS:
We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR 3.9-15.3). LN was associated with lower within-person mean eGFR [LN 93.8 (s.d. 26.4) vs non-LN 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median 157.0 (IQR 89.5, 268.9) vs non-LN median 84.9 (IQR 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance.CONCLUSION:
We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Canadá