Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis

Abstract

ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.

Lupus Nephritis Risk Factors and Biomarkers: An Update

“…Urinary cell membrane biomarkers useful in LN include the cell adhesion molecules (CAM) with vascular CAM1 (VCAM1) and activated leukocyte CAM (ALCAM), the neutrophil gelatinase-associated lipocalin (NGAL), the kidney injury molecule-1 (KIM-1), and the soluble (s)CD163 receptor shed from pro-inflammatory/fibrotic macrophages M2. In order to improve their performance, urinary levels can be normalized as the ratio with creatinuria, or less frequently with proteinuria or its serum fraction [120,121]. A combination of urinary biomarkers can be further used to discriminate proliferative LN from membranous LN [37].…”

Endothelial cell activation and glycocalyx shedding - potential as biomarkers in patients with lupus nephritis

“…Using aptamer-based screening followed by ELISA validation, urinary VCAM-1 was identified as a strong candidate to distinguish between active LN and quiescent disease irrespective of ethnicity ( 162 ). More recently, the assessment of urine: serum fractional excretion ratios of cell adhesion molecules outperformed corresponding urine and serum levels in identifying active LN from remission ( 163 ).…”