RAIL scores identify active LN, predict disease course in adult patients

The use of Renal Activity Index for Lupus (RAIL) score helps to detect active lupus nephritis (LN) and to calculate the course of adult LN, suggests a recent study.

“[T]hese findings support the clinical utility of the RAIL biomarkers and the RAIL score to noninvasively assess kidney inflammation and response to therapy in adult LN, to guide early treatment decisions, including identifying patients who may need therapy intensification, and thus allow for a personalized monitoring approach,” the researchers said.

Some 240 adults with biopsy-proven proliferative LN contributed a total of 599 serial urine samples collected up to week 52 for analysis. These samples were used to calculate RAIL scores from creatinine-adjusted urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), adiponectin, hemopexin, and ceruloplasmin.

The research team compared the discriminative performance of RAIL scores alone over time with urine protein/creatinine ratio (UPCR), kidney function (estimated glomerular filtration rate [eGFR]), and mixed model analysis of RAIL score, adjusting for baseline UPCR, eGFR, age, weight, sex, and rate.

Comparisons by renal response states were also conducted, including complete renal response (CRR), partial renal response but not CRR (PRR only), and nonresponse (NR).

Of the patients, 44, 22, and 15 showed PRR only; 27, 33, and 18 achieved CRR; and 127, 61, and 15 had NR at weeks 12, 24, and 52, respectively. [J Rheumatol 2026;53:283-291]

RAIL scores, eGFR, and UPCR improved over time regardless of abatacept use. However, these were significantly lower with CRR than NR. Furthermore, eGFR alone demonstrated poor accuracy (AUC <0.51) in discriminating renal response.

“Only after correction of baseline UPCR and eGFR, the RAIL score had excellent accuracy to reflect CRR from other renal response states at the current (AUC, 0.83‒0.84) and next visit (AUC, 0.84‒0.85) and performed better than UPCR,” the researchers said. “[W]ithout correction, UPCR and RAIL score had similarly good accuracy.”

Discrimination

Prior studies have shown that active LN can be differentiated from inactive or absent LN at scores ≥4.25, with an accuracy rate of 80 percent. Patients with CRR could be identified from those with NR at scores ≤4.18, consistent with previous observations. [Lupus 2017;26:927-936; Arthritis Care Res 2016;68:1003-1011]

Contrary to previous studies in adults with LN, the current results show that high RAIL scores at a given visit predict future NR of patients with LN. This finding supports prior analyses in children with LN, wherein RAIL score predicted the clinically observed course at least 3 months earlier. [J Rheumatol 2017;44:1239-1248; Arthritis Rheumatol 2022;74(Suppl 9)]

“Together, our findings might be exploited in clinical care for the surveillance of LN, especially in patients with known proteinuria from kidney damage in whom treatment resistance to the current treatment regimen is suspected,” the researchers said. “Indeed, RAIL scores that remain 6.5 or higher may indicate the need to adjust immunosuppressive therapy or explore nonadherence.”