Applying Genetic Risk Score to Improve Risk Assessment of New‐Onset Lupus Nephritis in Systemic Lupus Erythematosus: A Large‐Scale Prospective Cohort Study

Lupus nephritis (LN) is one of the most severe manifestation of systemic lupus erythematosus (SLE). However, reliable tools for predicting LN risk remain limited. In this multicenter prospective cohort study, we developed, validated, and refined a risk stratification model for new-onset LN. A total of 2441 SLE patients without baseline renal involvement were consecutively enrolled from the Chinese SLE Treatment and Research (CSTAR) registry, with 215 (8.8%) developed LN in a median follow-up time of 3.5 years. A combination of clinical predictors, age < 30 years, absence of arthritis, serositis, hypocomplementemia, and positive anti-double-stranded DNA antibodies identified a clinical high-risk group (<i>n</i> = 537, 22.0%) with a 3-year LN incidence of 18.1%. The model was externally validated in 451 patients, with 50 developed LN in a median follow-up time of 3.4 years. In these patients, a genetic risk score (GRS) derived from 112 SLE-associated loci was found to be independently associated with LN (HR = 3.19, 95% CI, 1.83-5.55, <i>p</i> = 4.36 × 10<sup>-5</sup>). Among clinically low-risk individuals, those in the highest GRS quartiles (81/451, 18.0%) showed elevated 3-year LN incidence (15.5% vs. 1.4%). New-onset LN may be predicted using a combination of clinical risk factors, and integrating GRS further improves risk stratification, enabling early identification of high-risk patients.

Authors

Institutions

Publication Details

Journal
MedComm
Published
2025-11-14
DOI
https://doi.org/10.1002/mco2.70453
Primary Topic
Systemic Lupus Erythematosus Research
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Applying Genetic Risk Score to Improve Risk Assessment of New‐Onset Lupus Nephritis in Systemic Lupus Erythematosus: A Large‐Scale Prospective Cohort Study

Junyan Qian, Xiaomei Leng, Jiuliang Zhao, Xinzhuang Yang et al.
MedComm
Systemic Lupus Erythematosus Research
article

Applying Genetic Risk Score to Improve Risk Assessment of New‐Onset Lupus Nephritis in Systemic Lupus Erythematosus: A Large‐Scale Prospective Cohort Study

Junyan Qian, Xiaomei Leng, Jiuliang Zhao, Xinzhuang Yang, Xinwang Duan, Hui Luo, Yang Xu, Mengzhuo Cao, Xinping Tian, Shangzhu Zhang, Pei Gao, Yufang Ding, Lijun Wu, Qian Wang, Wei Wei, Zhen Chen, Wei Bai, Jian Xu, Min Yang, Cheng Zhao, Xiaofeng Zeng, Mucong Li, Feng Zhan, Mengtao Li, Rui Wu
article en

Abstract

Lupus nephritis (LN) is one of the most severe manifestation of systemic lupus erythematosus (SLE). However, reliable tools for predicting LN risk remain limited. In this multicenter prospective cohort study, we developed, validated, and refined a risk stratification model for new-onset LN. A total of 2441 SLE patients without baseline renal involvement were consecutively enrolled from the Chinese SLE Treatment and Research (CSTAR) registry, with 215 (8.8%) developed LN in a median follow-up time of 3.5 years. A combination of clinical predictors, age < 30 years, absence of arthritis, serositis, hypocomplementemia, and positive anti-double-stranded DNA antibodies identified a clinical high-risk group (<i>n</i> = 537, 22.0%) with a 3-year LN incidence of 18.1%. The model was externally validated in 451 patients, with 50 developed LN in a median follow-up time of 3.4 years. In these patients, a genetic risk score (GRS) derived from 112 SLE-associated loci was found to be independently associated with LN (HR = 3.19, 95% CI, 1.83-5.55, <i>p</i> = 4.36 × 10<sup>-5</sup>). Among clinically low-risk individuals, those in the highest GRS quartiles (81/451, 18.0%) showed elevated 3-year LN incidence (15.5% vs. 1.4%). New-onset LN may be predicted using a combination of clinical risk factors, and integrating GRS further improves risk stratification, enabling early identification of high-risk patients.

MedCommVol. 6(12)
Fujian Medical University (CN), Ministry of Education of the People's Republic of China (CN), Central South University (CN), Nanchang University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Kunming Medical University (CN), Peking Union Medical College Hospital (CN), Tianjin Medical University General Hospital (CN), Karolinska Institutet (SE), Nanfang Hospital (CN), Second Affiliated Hospital of Nanchang University (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), First Affiliated Hospital of Kunming Medical University (CN), People's Hospital of Xinjiang Uygur Autonomous Region (CN), Hainan General Hospital (CN), Peking University First Hospital (CN), Second Affiliated Hospital of Fujian Medical University (CN), Second Xiangya Hospital of Central South University (CN), First Affiliated Hospital of Nanchang University (CN), Southern Medical University (CN)
National Natural Science Foundation of China, Peking Union Medical College Hospital
Openalex Percentile: Top 51%
Systemic Lupus Erythematosus Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.