Hermine I Brunner1,2, Michael R Bennett3,4, Gaurav Gulati3,4, Khalid Abulaban3,4, Marisa S Klein-Gitelman3,4, Stacy P Ardoin3,4, Lori B Tucker3,4, Kelly A Rouster-Stevens3,4, David Witte3,4, Jun Ying3,4, Prasad Devarajan3,4. 1. From the Division of Rheumatology, and the Division of Nephrology and Hypertension, and the Division of Pathology, Cincinnati Children's Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine; Division of Allergy and Rheumatology, Department of Medicine, and the Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, USA; Division of Rheumatology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada; DeVos Children's Hospital, Grand Rapids, Michigan; Department of Pediatrics, Division of Rheumatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Rheumatology, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio; Emory University, Division of Rheumatology, Department of Pediatrics, Atlanta, Georgia, USA. hermine.brunner@cchmc.org. 2. H.I. Brunner, MD, Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; M.R. Bennett, PhD, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; G. Gulati, MD, Division of Allergy and Rheumatology, Department of Medicine, University of Cincinnati; K. Abulaban, MD, Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, and DeVos Children's Hospital; M.S. Klein-Gitelman, MD, Department of Pediatrics, Division of Rheumatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine; S.P. Ardoin, MD, Division of Rheumatology, Department of Internal Medicine, Ohio State University Wexner Medical Center; L.B. Tucker, MBBS, Division of Rheumatology, Department of Pediatrics, British Columbia Children's Hospital; K.A. Rouster-Stevens, MD, Division of Rheumatology, Emory University, Department of Pediatrics; D. Witte, MD, Division of Pathology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; J. Ying, PhD; Department of Environmental Health, University of Cincinnati; P. Devarajan, MD, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine. hermine.brunner@cchmc.org. 3. From the Division of Rheumatology, and the Division of Nephrology and Hypertension, and the Division of Pathology, Cincinnati Children's Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine; Division of Allergy and Rheumatology, Department of Medicine, and the Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, USA; Division of Rheumatology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada; DeVos Children's Hospital, Grand Rapids, Michigan; Department of Pediatrics, Division of Rheumatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Rheumatology, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio; Emory University, Division of Rheumatology, Department of Pediatrics, Atlanta, Georgia, USA. 4. H.I. Brunner, MD, Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; M.R. Bennett, PhD, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; G. Gulati, MD, Division of Allergy and Rheumatology, Department of Medicine, University of Cincinnati; K. Abulaban, MD, Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, and DeVos Children's Hospital; M.S. Klein-Gitelman, MD, Department of Pediatrics, Division of Rheumatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine; S.P. Ardoin, MD, Division of Rheumatology, Department of Internal Medicine, Ohio State University Wexner Medical Center; L.B. Tucker, MBBS, Division of Rheumatology, Department of Pediatrics, British Columbia Children's Hospital; K.A. Rouster-Stevens, MD, Division of Rheumatology, Emory University, Department of Pediatrics; D. Witte, MD, Division of Pathology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine; J. Ying, PhD; Department of Environmental Health, University of Cincinnati; P. Devarajan, MD, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine.
Abstract
OBJECTIVE: To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN). METHODS: Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-β (TGF-β), transferrin, and vitamin D binding protein (VDBP). RESULTS: Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-β (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups. CONCLUSION: Low urine levels of TGF-β and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.
OBJECTIVE: To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN). METHODS: Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-β (TGF-β), transferrin, and vitamin D binding protein (VDBP). RESULTS: Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-β (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups. CONCLUSION: Low urine levels of TGF-β and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.
Authors: Brad H Rovin; Huijuan Song; Dan J Birmingham; Lee A Hebert; Chack Yung Yu; Haikady N Nagaraja Journal: J Am Soc Nephrol Date: 2004-12-15 Impact factor: 10.121
Authors: Y Avihingsanon; P Phumesin; T Benjachat; S Akkasilpa; V Kittikowit; K Praditpornsilpa; J Wongpiyabavorn; S Eiam-Ong; T Hemachudha; K Tungsanga; N Hirankarn Journal: Kidney Int Date: 2006-02 Impact factor: 10.612
Authors: Jan J Weening; Vivette D D'Agati; Melvin M Schwartz; Surya V Seshan; Charles E Alpers; Gerald B Appel; James E Balow; Jan A Bruijn; Terence Cook; Franco Ferrario; Agnes B Fogo; Ellen M Ginzler; Lee Hebert; Gary Hill; Prue Hill; J Charles Jennette; Norella C Kong; Philippe Lesavre; Michael Lockshin; Lai-Meng Looi; Hirofumi Makino; Luiz A Moura; Michio Nagata Journal: Kidney Int Date: 2004-02 Impact factor: 10.612
Authors: Jan J Weening; Vivette D D'Agati; Melvin M Schwartz; Surya V Seshan; Charles E Alpers; Gerald B Appel; James E Balow; Jan A Bruijn; Terence Cook; Franco Ferrario; Agnes B Fogo; Ellen M Ginzler; Lee Hebert; Gary Hill; Prue Hill; J Charles Jennette; Norella C Kong; Philippe Lesavre; Michael Lockshin; Lai-Meng Looi; Hirofumi Makino; Luiz A Moura; Michio Nagata Journal: J Am Soc Nephrol Date: 2004-02 Impact factor: 10.121
Authors: Hermine I Brunner; Gaurav Gulati; Marisa S Klein-Gitelman; Kelly A Rouster-Stevens; Lori Tucker; Stacey P Ardoin; Karen B Onel; Rylie Mainville; Jessica Turnier; Pinar Ozge Avar Aydin; David Witte; Bin Huang; Michael R Bennett; Prasad Devarajan Journal: Pediatr Nephrol Date: 2018-08-29 Impact factor: 3.714
Authors: Juan M Mejia-Vilet; Xiaolan L Zhang; Cristino Cruz; Mayra L Cano-Verduzco; John P Shapiro; Haikady N Nagaraja; Luis E Morales-Buenrostro; Brad H Rovin Journal: J Am Soc Nephrol Date: 2020-04-16 Impact factor: 10.121
Authors: Abril A Pérez-Arias; R Angélica Méndez-Pérez; Cristino Cruz; María Fernanda Zavala-Miranda; Juanita Romero-Diaz; Sofía E Márquez-Macedo; Roque A Comunidad-Bonilla; C Carolina García-Rueda; Juan M Mejía-Vilet Journal: Clin Rheumatol Date: 2022-09-15 Impact factor: 3.650
Authors: Ellen M Cody; Michael R Bennett; Gaurav Gulati; Qing Ma; Mekibib Altaye; Prasad Devarajan; Hermine I Brunner Journal: Kidney Int Rep Date: 2021-04-28