Clinical, Histologic, and Serological Predictors of Renal Function Loss in Lupus Nephritis
11 affiliations
- 1Johns Hopkins University School of Medicine Baltimore Maryland
- 2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China
- 3The University of Maryland School of Medicine Baltimore
- 4Oklahoma Medical Research Foundation Oklahoma City
- 5New York University School of Medicine New York
- 6Northwell Health Great Neck New York
- 7Albert Einstein College of Medicine Bronx New York
- 8Bar‐Ilan University Zefat Israel
- 9University of Rochester Medical Center Rochester New York
- 10University of California San Francisco
- 11University of Michigan Ann Arbor
Abstract
Objective: Kidney survival is the ultimate goal in lupus nephritis (LN) management, but long‐term predictors remain inadequately studied, requiring long‐term follow‐up. This study aimed to identify baseline and early longitudinal predictors of kidney survival in the Accelerating Medicines Partnership LN longitudinal cohort.
Methods: We performed time‐to‐event analyses of clinical, centrally scored histologic, and serological predictors of kidney function loss (sustained ≥40% estimated glomerular filtration rate [eGFR] decline or progression to end‐stage kidney disease) in 172 LN patients with a median follow‐up of 4.6 years (range 0.5–7.8).
Results: Kidney function loss occurred in 57 of 172 (33%) patients. Baseline lower eGFR, non‐first kidney biopsy, and higher National Institutes of Health (NIH) chronicity index were associated with eGFR loss. Chronicity index was the strongest predictor, but no clear threshold defined higher risk. NIH activity index and International Society of Nephrology (ISN) class were not predictive. Proteinuria at 12 months was prognostic, with urine protein‐to‐creatinine ratio <0.7 g/g associated with lower risk; however, no single threshold ensured protection, and lower levels had better outcomes. Lack of complete clinical response at 3, 6, or 12 months predicted future eGFR loss, whereas partial response conferred intermediate risk. Serological markers were not associated with eGFR loss.
Conclusion: Low baseline eGFR and chronic histologic damage, but not activity or ISN class, predicted eGFR loss. Proteinuria <0.7 g/g at one year was associated with better outcomes but did not ensure protection. Because proteinuria does not reflect intrarenal inflammation, these results suggest current response definitions serve better as prognostic indicators than true measures of treatment efficacy, and better biomarkers are needed.
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BibTeX
@article{zhang2026clinical,
title = {{Clinical, Histologic, and Serological Predictors of Renal Function Loss in Lupus Nephritis}},
author = {Shangzhu Zhang and Laurence Magder and Daniel Goldman and Judith A. James and Joel M. Guthridge and Carla Guthridge and Peter Izmirly and Jill P. Buyon and H. Michael Belmont and Richard A. Furie and Noa Schwartz and Chaim Putterman and Jennifer L. Barnas and Jennifer H. Anolik and Sarah French and Maria Dall'Era and Avi Z. Rosenberg and Jeffrey Hodgin and Dawit S. Demeke and the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network and Michelle Petri and Andrea Fava},
journal = {Arthritis Care \& Research},
year = {2026},
month = jun,
doi = {10.1002/acr.80070},
url = {https://doi.org/10.1002/acr.80070},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Clinical, Histologic, and Serological Predictors of Renal Function Loss in Lupus Nephritis
AU - Shangzhu Zhang
AU - Laurence Magder
AU - Daniel Goldman
AU - Judith A. James
AU - Joel M. Guthridge
AU - Carla Guthridge
AU - Peter Izmirly
AU - Jill P. Buyon
AU - H. Michael Belmont
AU - Richard A. Furie
AU - Noa Schwartz
AU - Chaim Putterman
AU - Jennifer L. Barnas
AU - Jennifer H. Anolik
AU - Sarah French
AU - Maria Dall'Era
AU - Avi Z. Rosenberg
AU - Jeffrey Hodgin
AU - Dawit S. Demeke
AU - the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network
AU - Michelle Petri
AU - Andrea Fava
PY - 2026
DA - 2026/06/09
JO - Arthritis Care & Research
DO - 10.1002/acr.80070
UR - https://doi.org/10.1002/acr.80070
AB - Objective: Kidney survival is the ultimate goal in lupus nephritis (LN) management, but long‐term predictors remain inadequately studied, requiring long‐term follow‐up. This study aimed to identify baseline and early longitudinal predictors of kidney survival in the Accelerating Medicines Partnership LN longitudinal cohort. Methods: We performed time‐to‐event analyses of clinical, centrally scored histologic, and serological predictors of kidney function loss (sustained ≥40% estimated glomerular filtration rate [eGFR] decline or progression to end‐stage kidney disease) in 172 LN patients with a median follow‐up of 4.6 years (range 0.5–7.8). Results: Kidney function loss occurred in 57 of 172 (33%) patients. Baseline lower eGFR, non‐first kidney biopsy, and higher National Institutes of Health (NIH) chronicity index were associated with eGFR loss. Chronicity index was the strongest predictor, but no clear threshold defined higher risk. NIH activity index and International Society of Nephrology (ISN) class were not predictive. Proteinuria at 12 months was prognostic, with urine protein‐to‐creatinine ratio <0.7 g/g associated with lower risk; however, no single threshold ensured protection, and lower levels had better outcomes. Lack of complete clinical response at 3, 6, or 12 months predicted future eGFR loss, whereas partial response conferred intermediate risk. Serological markers were not associated with eGFR loss. Conclusion: Low baseline eGFR and chronic histologic damage, but not activity or ISN class, predicted eGFR loss. Proteinuria <0.7 g/g at one year was associated with better outcomes but did not ensure protection. Because proteinuria does not reflect intrarenal inflammation, these results suggest current response definitions serve better as prognostic indicators than true measures of treatment efficacy, and better biomarkers are needed.
SN - 2151-464X
SN - 2151-4658
ER -