osteoprotegerin and Lupus-Nephritis

Urinary biomarkers may help in identification, treatment and assessment of response in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidneys and lymphoid cells and may reflect renal disease activity better. The data on its utility are sparse.. Fifty-eight patients with active LN (AN), 24 with active non-renal disease (ANR) and 39 with inactive disease (ID) were included. Median disease duration was 32 (1-204) months and median age was 27 (12-50) years. AN patients were followed up every three months for one year. Urine and serum samples were collected for OPG measurement by ELISA (pg/ml) and urinary values were normalised for creatinine excretion (pg/mg). Urine samples from 24 healthy individuals (HCs) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Variables were expressed as median (range).. At baseline, normalised urinary OPG (uOPG) was significantly higher (p < 0.001) in AN (1229 (0-8577)) than ANR (236 (0-14713)), ID (463 (7-4253)), HCs (366 (120-2849)) and DM (350 (127-1577)) but it was not different from RA (1511 (122-8849)). uOPG correlated modestly with rSLEDAI (r = 0.4, p < 0.001) and SLEDAI (r = 0.31, p < 0.001) but not with serum OPG (sOPG). uOPG but not sOPG could differentiate between AN and ANR groups. In the longitudinal study, uOPG and sOPG decreased significantly with treatment at all follow-up visits but the trend of fall in sOPG was erratic. uOPG values at baseline, 3, 6, 9 and 12 months were 1229 (0-8577), 466 (3-4874), 104 (0-1598), 325 (0-4025) and 555 (6-6771) pg/mg, respectively. uOPG but not sOPG rose before conventional markers in three patients who had a relapse of LN. In two patients who developed chronic kidney disease, uOPG remained persistently high. For differentiating AN from ANR patients, uOPG performed the best on receiver operator characteristics analysis (AUC = 0.72) when compared with anti-dsDNA antibodies, C3, C4 and sOPG.. uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.

Topics: Adolescent; Adult; Biomarkers; Child; Female; Humans; Longitudinal Studies; Lupus Nephritis; Male; Middle Aged; Osteoprotegerin; ROC Curve; Young Adult

This case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.. In 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.. Significantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).. Urinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Topics: Adult; Biomarkers; Case-Control Studies; Cohort Studies; Cytokine TWEAK; Disease Progression; Female; Humans; Interleukin-8; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Membrane Cofactor Protein; Molecular Targeted Therapy; Osteoprotegerin; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Tumor Necrosis Factors

Renal biopsy is the "gold standard" to determine renal activity in systemic lupus erythematosus (SLE), but it is expensive, invasive, and carries risk. Osteoprotegerin (OPG) is produced by the heart, lungs, kidney, and bone. Monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, is involved in the progression of glomerular and tubulointerstitial injury. We investigated both urine OPG and MCP-1 as potential biomarkers for lupus nephritis.. Our subjects, 87 patients with SLE (88% women; 48% African American, 41% Caucasian, 11% other), mean age 44 years, were followed monthly to quarterly. Urinary OPG (pg/ml) and MCP-1 (pg/ml) were measured (Luminex MAP bead assay).. OPG concentrations were strongly associated with global disease activity and with both renal activity on a visual analog scale (VAS) (p = 0.0006) and renal disease activity descriptors of the SELENA SLEDAI, including hematuria (p = 0.001) and a positive anti-dsDNA (p = 0.013). MCP-1 was also associated with the renal VAS (p = 0.032), renal disease activity descriptors of SELENA SLEDAI, including hematuria (p = 0.027), and with a positive anti-dsDNA (p = 0.016). We also examined the relationship between the biomarkers and having a urine protein to creatinine ratio (pr/cr) > or = 0.5. Among patients with medium or high OPG, 46% had urine pr/cr > or = 0.5, compared to only 23% among those with low OPG (p = 0.032). The 2 biomarkers were strongly correlated with each other (Spearman correlation coefficient 0.77, p < 0.0001).. The lack of availability of urine biomarkers has hampered development of new therapies for lupus nephritis. Urine MCP-1 and OPG were both associated with measures of lupus renal disease activity. Medium or high levels of OPG were predictive of a urine protein/creatinine ratio of > or = 0.5. Further study, including longitudinal assessment and correlation with concurrent renal biopsies, is necessary before this assay can be used in the routine clinic setting.

Topics: Adult; Aged; Biomarkers; Biopsy; Chemokine CCL2; Cohort Studies; Creatinine; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney; Longitudinal Studies; Lupus Nephritis; Male; Middle Aged; Osteoprotegerin; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index