A urine biomarker–based score could help predict kidney inflammation and treatment response over time in patients with lupus nephritis, according to a recent study.
The Renal Activity Index for Lupus (RAIL) was evaluated in an exploratory analysis of the randomized, controlled phase III ALLURE trial, which enrolled patients with biopsy-proven active proliferative lupus nephritis. Researchers analyzed 240 patients who contributed 599 urine samples collected through 52 weeks. RAIL scores were calculated from six urine biomarkers, including neutrophil gelatinase–associated lipocalin, kidney injury molecule 1, monocyte chemotactic protein 1, adiponectin, hemopexin, and ceruloplasmin normalized to urine creatinine concentrations. The patients received standard therapy with or without abatacept.
The researchers assessed the ability of RAIL to distinguish renal response states—complete renal response, partial renal response, or nonresponse—at each visit as well as the ability of RAIL to predict renal response at the subsequent visit compared with the urine protein/creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR).
Main results
RAIL scores decreased over time and were lower in patients who achieved complete renal response compared with nonresponders at multiple timepoints. After adjustment for baseline clinical factors, the RAIL index demonstrated accuracy in identifying complete renal response, with area under the receiver-operating characteristic curve values of 0.83 to 0.84 at the same visit and 0.84 to 0.85 for predicting response at the next visit.
Secondary findings
The RAIL index outperformed eGFR, which showed little ability to distinguish renal response, with values near 0.50 across the analyses. UPCR demonstrated moderate performance and, without adjustment, performed similarly to the RAIL index. After adjustment for baseline characteristics, however, the RAIL index showed improved discrimination compared with UPCR in identifying complete renal response.
Higher RAIL scores at a given visit were associated with nonresponse at the next visit, whereas lower scores were associated with subsequent complete renal response, indicating the score's predictive value across visits.
No meaningful differences in RAIL trends were observed between patients receiving abatacept and those receiving placebo, consistent with the parent trial, which didn't show improved complete renal response rates with abatacept.
Nuance
Without adjustment for baseline factors, the RAIL index and UPCR showed similar accuracy, suggesting that the incremental value of the RAIL index may depend on accounting for clinical context. Additionally, the improvements in RAIL scores over time across all groups reflected overall treatment response rather than treatment-specific effects.
Limitations
The study didn't include repeat kidney biopsies, limiting the direct comparison of biomarker changes with histologic disease activity. The number of patients with available samples declined over time, particularly by week 52, which may have affected the stability of long-term estimates. The analysis was conducted within a clinical trial population, which may have limited generalizability to routine clinical settings.
Conclusion
The findings supported the RAIL index as a noninvasive tool to assess disease activity and anticipate treatment response in patients with lupus nephritis alongside existing clinical measures.
“RAIL scores identify active [lupus nephritis] and longitudinally predict the course of adult [patients with lupus nephritis],” wrote lead study author Shannon K. O’Connor, MD, PhD, of the Department of Pediatrics in the Division of Pediatric Rheumatology at the Cincinnati Children’s Hospital Medical Center at the University of Cincinnati, and colleagues.
The study was supported by the National Institutes of Health, Pfizer, the Center for Clinical and Translational Science and Training at the University of Cincinnati, and the National Institutes of Arthritis and Musculoskeletal Skin Diseases. Full disclosures of the study authors can be found in the study.
Source: The Journal of Rheumatology
