Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis

Abstract

BackgroundThe aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE).MethodPatients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested.ResultsPatients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup.ConclusionsUrinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.

Urinary Soluble VCAM-1 is a Useful Biomarker of Disease Activity and Treatment Response in Lupus Nephritis

“…In agreement with the work from MoK CC et al (20), we observed no difference between uVCAM-1 levels and nephritis class (proliferative with or without membranous vs pure membranous). We decide not to include patients with class I and II nephritis, which were not associated with VCAM-1 elevation in previous studies (14,20). Some studies showed that elevated uVCAM-1 is not speci c for SLE.…”

Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis

“…The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 for all the participants and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and speci city (74.2%) to differentiate active LN versus non active LN. Mok CC and colleagues (20) found different values from ours. An AUC 0.73 and a cutoff of 668 pg/ngCr yielded sensitivity of 66% and speci city of 69% to differentiate between active renal and non-renal active SLE, a different comparison from that performed in our study.…”

“…Urinary VCAM-1 levels were signi cantly elevated in patients with SLE compared to healthy controls (18,19). Previous studies have also shown higher levels of uVCAM-1 in patients with SLE and LN compared to SLE without LN with similar general disease activity assessed through the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (20,21). Several studies correlated the uVCAM-1 levels with UPCR, with SLEDAI (18,19) and with active LN (22,23).…”

Prediction of prognosis and renal outcome in lupus nephritis

“…In parallel with drug research, identification of serum and urinary non-invasive biomarkers that accurately reflect renal activity at the level of tissue and predict long-term renal outcome have been a topic of extensive study during the last decades 51. Investigations include single-molecule evaluations52–57 and large semi-unbiased proteomic screenings58 of serum markers, while urinary biomarkers receive increasing interest59–62 for two important reasons. First, molecules in urine are likely to be directly excreted from the kidney, which makes them highly relevant in the context of LN and other renal disorders.…”