PMID- 22328173 OWN - NLM STAT- MEDLINE DCOM- 20121203 LR - 20220317 IS - 1529-0131 (Electronic) IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 64 IP - 8 DP - 2012 Aug TI - Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis. PG - 2687-97 LID - 10.1002/art.34426 [doi] AB - 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), alpha(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). CONCLUSION: 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. CI - Copyright (c) 2012 by the American College of Rheumatology. FAU - Brunner, Hermine I AU - Brunner HI AD - Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. hermine.brunner@cchmc.org FAU - Bennett, Michael R AU - Bennett MR FAU - Mina, Rina AU - Mina R FAU - Suzuki, Michiko AU - Suzuki M FAU - Petri, Michelle AU - Petri M FAU - Kiani, Adnan N AU - Kiani AN FAU - Pendl, Joshua AU - Pendl J FAU - Witte, David AU - Witte D FAU - Ying, Jun AU - Ying J FAU - Rovin, Brad H AU - Rovin BH FAU - Devarajan, Prasad AU - Devarajan P LA - eng GR - DK-074661/DK/NIDDK NIH HHS/United States GR - U01 AR059509-02/AR/NIAMS NIH HHS/United States GR - DK-077331/DK/NIDDK NIH HHS/United States GR - R21 DK077331/DK/NIDDK NIH HHS/United States GR - P60-AR-47784/AR/NIAMS NIH HHS/United States GR - U01 AR055054-03S1/AR/NIAMS NIH HHS/United States GR - P60 AR047784-09/AR/NIAMS NIH HHS/United States GR - R01 DK074661/DK/NIDDK NIH HHS/United States GR - UL1 TR000077-04/TR/NCATS NIH HHS/United States GR - UL1 TR000077/TR/NCATS NIH HHS/United States GR - U01 AR059509/AR/NIAMS NIH HHS/United States GR - AR-43727/AR/NIAMS NIH HHS/United States GR - P30 AR047363/AR/NIAMS NIH HHS/United States GR - R01 DK053289/DK/NIDDK NIH HHS/United States GR - P30 AR047363-08/AR/NIAMS NIH HHS/United States GR - R01 DK053289-05/DK/NIDDK NIH HHS/United States GR - UL1 RR025005/RR/NCRR NIH HHS/United States GR - UL1 RR025005-05/RR/NCRR NIH HHS/United States GR - UL1-RR-025005/RR/NCRR NIH HHS/United States GR - R01-DK53289/DK/NIDDK NIH HHS/United States GR - P30-AR-047363/AR/NIAMS NIH HHS/United States GR - P30 AR047363-09/AR/NIAMS NIH HHS/United States GR - R21 DK077331-02/DK/NIDDK NIH HHS/United States GR - U01-AR-059509/AR/NIAMS NIH HHS/United States GR - R01 DK053289-04/DK/NIDDK NIH HHS/United States GR - R01 AR043727-13/AR/NIAMS NIH HHS/United States GR - U01 AR059509-03/AR/NIAMS NIH HHS/United States GR - P60 AR047784-10/AR/NIAMS NIH HHS/United States GR - U01 AR055054/AR/NIAMS NIH HHS/United States GR - R01 AR043727/AR/NIAMS NIH HHS/United States GR - P50 DK096418/DK/NIDDK NIH HHS/United States GR - U01 AR059509-01/AR/NIAMS NIH HHS/United States GR - P60 AR047784/AR/NIAMS NIH HHS/United States GR - P30 AR047363-10/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Acute-Phase Proteins) RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (LCN2 protein, human) RN - 0 (Lipocalin-2) RN - 0 (Lipocalins) RN - 0 (Orosomucoid) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Transferrin) RN - AYI8EX34EU (Creatinine) RN - EC 1.16.3.1 (Ceruloplasmin) SB - IM MH - Acute-Phase Proteins/*urine MH - Adolescent MH - Adult MH - Biomarkers/urine MH - Biopsy MH - Ceruloplasmin/*urine MH - Chemokine CCL2/*urine MH - Child MH - Cohort Studies MH - Creatinine/*urine MH - Female MH - Fibrosis MH - Humans MH - Kidney/pathology/physiopathology MH - Lipocalin-2 MH - Lipocalins/*urine MH - Logistic Models MH - Lupus Nephritis/*pathology/urine MH - Male MH - Middle Aged MH - Necrosis MH - Orosomucoid/*urine MH - Proto-Oncogene Proteins/*urine MH - ROC Curve MH - Retrospective Studies MH - Transferrin/*urine MH - Young Adult PMC - PMC3381849 MID - NIHMS355370 COIS- Conflict of Interest Statement Dr. Devarajan is a co-inventor on NGAL patents for the diagnosis of acute kidney injury. Dr. Devarajan and Brunner are co-inventors on patents covering biomarker panels for the diagnosis of lupus nephritis. EDAT- 2012/02/14 06:00 MHDA- 2012/12/10 06:00 PMCR- 2013/08/01 CRDT- 2012/02/14 06:00 PHST- 2012/02/14 06:00 [entrez] PHST- 2012/02/14 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - 10.1002/art.34426 [doi] PST - ppublish SO - Arthritis Rheum. 2012 Aug;64(8):2687-97. doi: 10.1002/art.34426.