Abstract: SA-PO929
Genetic Determinants of Lupus Nephritis and Kidney Function in Systemic Lupus Erythematosus
Session Information
- Glomerular Diseases: Translational Studies and Biomarkers
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Riedl Khursigara, Magdalena, The Hospital for Sick Children, Toronto, Ontario, Canada
- Gold, Nicholas, The Hospital for Sick Children, Toronto, Ontario, Canada
- Dominguez, Daniela, The Hospital for Sick Children, Toronto, Ontario, Canada
- Levy, Deborah, The Hospital for Sick Children, Toronto, Ontario, Canada
- Noone, Damien Gerard, The Hospital for Sick Children, Toronto, Ontario, Canada
- Cao, Jingjing, The Hospital for Sick Children, Toronto, Ontario, Canada
- Urowitz, Murray B., Krembil Research Institute, Toronto, Ontario, Canada
- Onel, Karen Special, Hospital for Special Surgery, New York, New York, United States
- Harvey, Elizabeth A., The Hospital for Sick Children, Toronto, Ontario, Canada
- Lee, Chia-Chi J., Cedars-Sinai Medical Center, Los Angeles, California, United States
- Jefferies, Caroline, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Wither, Joan, University Health Network, Toronto, Ontario, Canada
- Kamen, Diane L., Medical University of South Carolina, Charleston, South Carolina, United States
- Pope, Janet, London Health Sciences Centre, London, Ontario, Canada
- Peschken, Christine A., University of Manitoba, Winnipeg, Manitoba, Canada
- Petri, Michelle, Johns Hopkins University, Baltimore, Maryland, United States
- Goldman, Daniel W., Johns Hopkins University, Baltimore, Maryland, United States
- Tang, Thai-Son, The Hospital for Sick Children, Toronto, Ontario, Canada
- Ishimori, Mariko, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Knight, Andrea, The Hospital for Sick Children, Toronto, Ontario, Canada
- Silverman, Earl, University Health Network, Toronto, Ontario, Canada
- Hiraki, Linda T., The Hospital for Sick Children, Toronto, Ontario, Canada
Group or Team Name
- Systemic Lupus Erythematosus Collaborative Clinics (SLICC).
Background
Lupus nephritis (LN) is one of the most common and severe manifestations of SLE. We completed an LN genome wide association study (GWAS) in a multi-ethnic cohort of children and adults with SLE.
Methods
We included SLE patients from dedicated Lupus clinics and the SLICC cohort. All patients met ACR and/or SLICC SLE classification criteria and were genotyped on a multi-ethnic Illumina array. LN was defined by SLE criteria. Kidney function (eGFR) was estimated using the Schwartz Bedside formula for measures <18 years and CKD-EPI (without ancestry) for >18 years of age, collected longitudinally over time. Wilcoxon rank sum or Chi-square test were used for significance between LN and Non-LN patients. We completed GWAS of LN in marginal and multivariable adjusted regression models with principal components for ancestry, sex and cohort site.
Results
We included 2981 patients with SLE, 88% female, 46% of European ancestry, 27% childhood-onset SLE. LN was present in 45%. People at time of LN diagnosis were younger and more likely of African American or East Asian ancestry. People with LN had significantly lower within-person mean eGFR, greater eGFR variability and slope over time compared to those without LN (Table). GWAS of LN demonstrated a peak on chromosome 8, yet did not reach a genome-wide significance (p < 5x10-8).
Conclusion
Our GWAS did not identify a significant locus for LN. We plan to repeat GWAS of repeated eGFR measures, as it is a more informative outcome that may improve power for detecting genetic loci for LN.
Characteristics of LN and Non-LN patients
| Patient Characteristics | All SLE Patients (n=2981) | LN SLE Patients (n=1351) | Non-LN SLE Patients (n=1630) | P-value |
| Sex, Female | 2628 (88.2) | 1138 (84.2) | 1490 (91.4) | 1.6e-09 |
| Age at SLE diagnosis (years) | 25.6 [16.4, 37.8] | 22.6 [15.7, 33.0] | 28.3 [17.3, 41.3] | 2.2e-16 |
| cSLE diagnosis | 814 (27.3) | 484 (35.8) | 440 (27.0) | 2.1e-07 |
| Inferred Ancestry European East Asian African American South Asian Admixed | 1367 (45.9) 459 (15.4) 555 (18.6) 151 (5.1) 131 (4.4) 317 (10.6) | 493 (36.5) 252 (18.6) 316 (23.3) 80 (5.9) 68 (5.0) 141 (10.4) | 874 (53.6) 207 (12.7) 239 (14.7) 71 (4.4) 63 (3.9) 176 (10.8) | 2.2e-16 |
| Hypertension* | 1017 (37.1) | 659 (52.6) | 358 (23.8) | 2.2e-16 |
| Kidney failure (chronic dialysis or transplant)* | 25 (0.9) | 25 (2.0) | 0 (0.0) | 3.0e-08 |
| Time from diagnosis to 1st eGFR (years)* Time from 1st eGFR measurement to last (years)* | 0.6 [0.06, 3.4] 8.9 [4.1, 14.8] | 0.6 [0.08, 3.8] 10.0 [5.1, 16.1] | 0.5 [0.04, 3.0] 7.8 [3.4, 13.7] | 3.3e-01 4.4e-13 |
| Within-Person No. eGFR Measures* | 16 [8, 35] | 21 [10, 45] | 13 [6, 29] | 2.2e-16 |
| Within-Person mean* Within-Person eGFR Variance* eGFR slope ml/min/1.73m2/y* | 100.8 [86.0, 113.1] 106.6 [51.4, 198.7] -0.53 [-2.00, 0.48] | 100.2 [81.3, 113.4] 137.2 [69.6, 268.6] -0.67 [-2.26, 0.36] | 101.2 [88.6, 112.7] 87.2 [43.1, 156.4] -0.53 [-1.83, 0.67] | 7.7e-02 2.2e-16 2.3e-02 |
* data available for N= 2740
Funding
- Government Support – Non-U.S.