Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis

Abstract

Objectives: Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis.

Methods: Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort.

Results: uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort.

Conclusions: uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.

Fig. 1

ROC curve constructed for uNGAL and the development of renal flare in patients with a history of biopsy-proven LN. The curve depicts the specificity and sensitivity of a preceding visit’s uNGAL level for renal flare (defined as an increase of ≥4 points on the renal SLEDAI score). The AUC is 0.7639, significantly greater than the AUC from an ROC curve of anti-dsDNA titres (P = 0.004) and similar to the AUC from ROC curves of C3 and C4 levels.