Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis.
OBJECTIVE
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Kiani
Adnan N
AN
Division of Rheumatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Baltimore, MD 21205, USA.
Johnson
Kristen
K
Chen
Catherine
C
Diehl
Edward
E
Hu
Huaizhong
H
Vasudevan
Ganesh
G
Singh
Sukhminder
S
Magder
Laurence S
LS
Knechtle
Stuart J
SJ
Petri
Michelle
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D018932:Chemokine CCL2 / Q000652:urine*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000473:pathology; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000503:physiopathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000652:urine*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053244:Osteoprotegerin; D003404:Creatinine