Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis.
OBJECTIVE
To investigate the relationship of urinary biomarkers and established measures of renal function to histologic findings in lupus nephritis (LN), and to test whether certain combinations of the above-mentioned laboratory measures are diagnostic for specific histologic features of LN.


METHODS
Urine samples from 76 patients were collected within 2 months of kidney biopsy and assayed for the urinary biomarkers lipocalin-like prostaglandin D synthase (L-PGDS), α(1) -acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1). Using nonparametric analyses, levels of urinary biomarkers and established markers of renal function were compared with histologic features seen in LN, i.e., mesangial expansion, capillary proliferation, crescent formation, necrosis, wire loops, fibrosis, tubular atrophy, and epimembranous deposits. The area under the receiver operating characteristic curve (AUC) was calculated to predict LN activity, chronicity, or membranous LN.


RESULTS
There was a differential increase in levels of urinary biomarkers that formed a pattern reflective of specific histologic features seen in active LN. The combination of MCP-1, AAG, and CP levels plus protein:creatinine ratio was excellent in predicting LN activity (AUC 0.85). NGAL together with creatinine clearance plus MCP-1 was an excellent diagnostic test for LN chronicity (AUC 0.83), and the combination of MCP-1, AAG, TF, and creatinine clearance plus C4 was a good diagnostic test for membranous LN (AUC 0.75).


CONCLUSIONS
Specific urinary biomarkers are associated with specific tissue changes observed in conjunction with LN activity and chronicity. Especially in combination with select established markers of renal function, urinary biomarkers are well-suited for use in noninvasive measurement of LN activity, LN chronicity, and the presence of membranous LN.
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. hermine.brunner@cchmc.org
Hermine I
HI
Brunner
Michael R
MR
Bennett
Rina
R
Mina
Michiko
M
Suzuki
Michelle
M
Petri
Adnan N
AN
Kiani
Joshua
J
Pendl
David
D
Witte
Jun
J
Ying
Brad H
BH
Rovin
Prasad
P
Devarajan
D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D002570:Ceruloplasmin / Q000652:urine*; D018932:Chemokine CCL2 / Q000652:urine*; D002648:Child; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D016015:Logistic Models; D008181:Lupus Nephritis / Q000473:pathology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009961:Orosomucoid / Q000652:urine*; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012372:ROC Curve; D012189:Retrospective Studies; D014168:Transferrin / Q000652:urine*; D055815:Young Adult
D000209:Acute-Phase Proteins; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D009961:Orosomucoid; D011518:Proto-Oncogene Proteins; D014168:Transferrin; D003404:Creatinine; D002570:Ceruloplasmin