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Kidney Week

Abstract: SA-PO929

Genetic Determinants of Lupus Nephritis and Kidney Function in Systemic Lupus Erythematosus

Session Information

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 CharacteristicsAll SLE Patients (n=2981)LN SLE Patients (n=1351)Non-LN SLE Patients (n=1630)P-value
Sex, Female2628 (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 diagnosis814 (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.