. 2022 Nov 2;61(11):4335-4343.

doi: 10.1093/rheumatology/keac067.

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership

Philip M Carlucci¹, Jessica Li², Andrea Fava², Kristina K Deonaraine¹, David Wofsy³, Judith A James⁴, Chaim Putterman^{5

6}, Betty Diamond⁷, Anne Davidson⁷, Derek M Fine⁸, Jose Monroy-Trujillo⁸, Mohamed G Atta⁸, Wade DeJager⁴, Joel M Guthridge⁴, Kristin Haag², Deepak A Rao⁹, Michael B Brenner⁹, James A Lederer⁹, William Apruzzese⁹, H Michael Belmont¹, Peter M Izmirly¹, Devyn Zaminski¹, Ming Wu¹, Sean Connery¹⁰, Fernanda Payan-Schober¹⁰, Richard Furie¹¹, Maria Dall'Era³, Kerry Cho¹², Diane Kamen¹³, Kenneth Kalunian¹⁴, Jennifer Anolik¹⁵, Jennifer Barnas¹⁵, Mariko Ishimori¹⁶, Michael H Weisman¹⁶; Accelerating Medicines Partnership (AMP) RA/SLE Network; Jill P Buyon¹, Michelle Petri²

Collaborators, Affiliations

Collaborators

Accelerating Medicines Partnership (AMP) RA/SLE Network:
Jennifer Goff, Patrick J Dunn, Soumya Raychaudhuri, Fan Zhang, Ilya Korsunsky, Aparna Nathan, Joseph Mears, Kazuyoshi Ishigaki, Qian Xiao, Nghia Millard, Kathryn Weinand, Saori Sakaue, P J Utz, Rong Mao, Bill Robinson, Holden Maecker, Susan Macwana, S Louis Bridges, Vivian Bykerk, Laura Donlin, Susan Goodman, Edward DiCarlo, Melanie Smith, Amit Lakhanpal, Heather Sherman, Anvita Singaraju, Lorien Shakib, Christopher Ritchlin, Brendan Boyce, Darren Tabechian, Andrew McDavid, Javier Rangel-Moreno, Nida Meednu, Jen Albrecht, Kevin Wei, A Helena Jonsson, Daimon Simmons, Gregory Keras, Joshua Keegan, Gerald Watts, Yuhong Li Zhu, Adam Chicoine, Zhihan Jian Li, Ellen M Gravallese, Kaitlyn Howard, Mandy McGeachy, Gary S Firestein, David L Boyle, Arnold Ceponis, Peter K Gregersen, Diane Horowitz, Harris Perlman, Salina Dominguez, Carla M Cuda, Arthur M Mandolin, Anjali Thakrar, Joan M Bathon, Laura Hughes, V Michael Holers, Jennifer Seifert, Kevin Deane, Larry W Moreland, Andrew Filer, Karim Raza, Ilfita Sahbudin, Costantino Pitzalis, Myles Lewis, Felice Rivellese, Alessandra Nerviani, Michele Bombardieri, Lindsy Forbess, Ami Ben-Artzi, Karen Salomon-Escoto, Arnon Arazi, Raymond Hsu, Robert Clancy, Beatrice Goilav, David A Hildeman, E Steve Woodle, Nir Hacohen, Paul Hoover, Thomas Eisenhaure, Michael Peters, Tony Jones, David Lieb, Thomas Tuschl, Hemant Suryawanshi, Pavel Morozov, Manjunath Kustagi, Maureen A McMahon, Jennifer Grossman, Matthias Kretzler, Celine C Berthier, Jeffrey B Hodgin, Raji Menon

Affiliations

¹ Department of Medicine, New York University School of Medicine, New York, NY.
² Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
³ Rheumatology Division, Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, CA.
⁴ Department of Medicine, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK.
⁵ Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
⁶ Azrieli Faculty of Medicine, Bar-Ilan University, Zefat, Israel.
⁷ Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY.
⁸ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
⁹ Division of Rheumatology, Inflammation, Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
¹⁰ Department of Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX.
¹¹ Division of Rheumatology, Department of Medicine, Northwell Health, Great Neck, NY.
¹² Nephrology Division, Department of Medicine, University of California San Francisco, San Francisco, CA.
¹³ Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC.
¹⁴ Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA.
¹⁵ Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY.
¹⁶ Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

PMID: 35212719
PMCID: PMC9629353
DOI: 10.1093/rheumatology/keac067

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership

Philip M Carlucci et al. Rheumatology (Oxford). 2022.

. 2022 Nov 2;61(11):4335-4343.

doi: 10.1093/rheumatology/keac067.

Authors

Collaborators

Accelerating Medicines Partnership (AMP) RA/SLE Network:
Jennifer Goff, Patrick J Dunn, Soumya Raychaudhuri, Fan Zhang, Ilya Korsunsky, Aparna Nathan, Joseph Mears, Kazuyoshi Ishigaki, Qian Xiao, Nghia Millard, Kathryn Weinand, Saori Sakaue, P J Utz, Rong Mao, Bill Robinson, Holden Maecker, Susan Macwana, S Louis Bridges, Vivian Bykerk, Laura Donlin, Susan Goodman, Edward DiCarlo, Melanie Smith, Amit Lakhanpal, Heather Sherman, Anvita Singaraju, Lorien Shakib, Christopher Ritchlin, Brendan Boyce, Darren Tabechian, Andrew McDavid, Javier Rangel-Moreno, Nida Meednu, Jen Albrecht, Kevin Wei, A Helena Jonsson, Daimon Simmons, Gregory Keras, Joshua Keegan, Gerald Watts, Yuhong Li Zhu, Adam Chicoine, Zhihan Jian Li, Ellen M Gravallese, Kaitlyn Howard, Mandy McGeachy, Gary S Firestein, David L Boyle, Arnold Ceponis, Peter K Gregersen, Diane Horowitz, Harris Perlman, Salina Dominguez, Carla M Cuda, Arthur M Mandolin, Anjali Thakrar, Joan M Bathon, Laura Hughes, V Michael Holers, Jennifer Seifert, Kevin Deane, Larry W Moreland, Andrew Filer, Karim Raza, Ilfita Sahbudin, Costantino Pitzalis, Myles Lewis, Felice Rivellese, Alessandra Nerviani, Michele Bombardieri, Lindsy Forbess, Ami Ben-Artzi, Karen Salomon-Escoto, Arnon Arazi, Raymond Hsu, Robert Clancy, Beatrice Goilav, David A Hildeman, E Steve Woodle, Nir Hacohen, Paul Hoover, Thomas Eisenhaure, Michael Peters, Tony Jones, David Lieb, Thomas Tuschl, Hemant Suryawanshi, Pavel Morozov, Manjunath Kustagi, Maureen A McMahon, Jennifer Grossman, Matthias Kretzler, Celine C Berthier, Jeffrey B Hodgin, Raji Menon

Affiliations

¹ Department of Medicine, New York University School of Medicine, New York, NY.
² Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
³ Rheumatology Division, Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, CA.
⁴ Department of Medicine, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK.
⁵ Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
⁶ Azrieli Faculty of Medicine, Bar-Ilan University, Zefat, Israel.
⁷ Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY.
⁸ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
⁹ Division of Rheumatology, Inflammation, Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
¹⁰ Department of Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX.
¹¹ Division of Rheumatology, Department of Medicine, Northwell Health, Great Neck, NY.
¹² Nephrology Division, Department of Medicine, University of California San Francisco, San Francisco, CA.
¹³ Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC.
¹⁴ Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA.
¹⁵ Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY.
¹⁶ Division of Rheumatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

PMID: 35212719
PMCID: PMC9629353
DOI: 10.1093/rheumatology/keac067

Abstract

Objective: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.

Methods: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.

Results: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year.

Conclusion: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.

Keywords: diagnosis; lupus nephritis; systemic lupus erythematosus.

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Figures

<sc>Fig</sc>. 1 — **Fig. 1**
Change in UPCR over 1 year for patients with baseline UPCR <1 (A) UPCR at baseline (n = 8), 6 months (n = 5) and 1 year (n = 7) for patients with baseline UPCR <1 and class II renal histology. (B) UPCR at baseline (n = 29), 6 months (n = 28) and 1 year (n = 29) for patients with baseline UPCR <1 and class III, IV, V or mixed renal histology. UPCR: urine protein:creatinine ratio.

See this image and copyright information in PMC

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High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership

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High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership

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