High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership
Authors: Carlucci Philip M , Li Jessica , Fava Andrea , Deonaraine Kristina K , Wofsy David , James Judith A , Putterman Chaim , Diamond Betty , Davidson Anne , Fine Derek M , Monroy-Trujillo Jose , Atta Mohamed G , DeJager Wade , Guthridge Joel M , Haag Kristin , Rao Deepak A , Brenner Michael B , Lederer James A , Apruzzese William , Belmont H Michael , Izmirly Peter M , Zaminski Devyn , Wu Ming , Connery Sean , Payan-Schober Fernanda , Furie Richard , Dall’Era Maria , Cho Kerry , Kamen Diane , Kalunian Kenneth , Anolik Jennifer , Barnas Jennifer , Ishimori Mariko , Weisman Michael H ,   the Accelerating Medicines Partnership (AMP) RA/SLE Network, Goff Jennifer , Dunn Patrick J , Raychaudhuri Soumya , Zhang Fan , Korsunsky Ilya , Nathan Aparna , Mears Joseph , Ishigaki Kazuyoshi , Xiao Qian , Millard Nghia , Weinand Kathryn , Sakaue Saori , Utz P J , Mao Rong , Robinson Bill , Maecker Holden , Macwana Susan , Bridges S Louis , Bykerk Vivian , Donlin Laura , Goodman Susan , DiCarlo Edward , Smith Melanie , Lakhanpal Amit , Sherman Heather , Singaraju Anvita , Shakib Lorien , Ritchlin Christopher , Boyce Brendan , Tabechian Darren , McDavid Andrew , Rangel-Moreno Javier , Meednu Nida , Albrecht Jen , Wei Kevin , Helena Jonsson A , Simmons Daimon , Keras Gregory , Keegan Joshua , Watts Gerald , Li Zhu Yuhong , Chicoine Adam , Jian Li Zhihan , Gravallese Ellen M , Howard Kaitlyn , McGeachy Mandy , Firestein Gary S , Boyle David L , Ceponis Arnold , Gregersen Peter K , Horowitz Diane , Perlman Harris , Dominguez Salina , Cuda Carla M , Mandolin Arthur M , Thakrar Anjali , Bathon Joan M , Hughes Laura , Michael Holers V , Seifert Jennifer , Deane Kevin , Moreland Larry W , Filer Andrew , Raza Karim , Sahbudin Ilfita , Pitzalis Costantino , Lewis Myles , Rivellese Felice , Nerviani Alessandra , Bombardieri Michele , Forbess Lindsy , Ben-Artzi Ami , Salomon-Escoto Karen , Arazi Arnon , Hsu Raymond , Clancy Robert , Goilav Beatrice , Hildeman David A , Steve Woodle E , Hacohen Nir , Hoover Paul , Eisenhaure Thomas , Peters Michael , Jones Tony , Lieb David , Tuschl Thomas , Suryawanshi Hemant , Morozov Pavel , Kustagi Manjunath , McMahon Maureen A , Grossman Jennifer , Kretzler Matthias , Berthier Celine C , Hodgin Jeffrey B , Menon Raji , Buyon Jill P , Petri Michelle 
Published: January 2022

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 &lt;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 &lt;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 &lt;1. Of 29 patients with baseline UPCR &lt;1 and class III, IV, V or mixed, 23 (79%) had a UPCR &lt;0.5 at 1 year.

Conclusion

In this prospective study, three-quarters of patients with UPCR &lt;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.