Longitudinal Outcomes of COVID-19–Associated Collapsing Glomerulopathy and Other Podocytopathies
Authors: Kudose Satoru , Santoriello Dominick , Bomback Andrew S. , Sekulic Miroslav , Batal Ibrahim , Stokes M. Barry , Ghavami Iman A. , Kim Jung S. , Marasa Maddalena , Xu Katherine , Peleg Yonatan , Barasch Jonathan , Canetta Pietro , Rasouly Hila Milo , Gharavi Ali G. , Markowitz Glen S. , D’Agati Vivette D. 
Published: October 2021

Significance Statement
Long-term outcome of COVID-19–associated collapsing glomerulopathy is unknown. In this study of 23 patients, most were Black, had mild to moderate COVID-19, and presented with nephrotic-range proteinuria and AKI, requiring dialysis in 14 (61%). Immunostaining and in situ hybridization did not detect direct viral infection of the kidney. Of 17 genotyped patients, 16 (94%) had a high-risk APOL1 genotype. Among 22 patients (96%) with follow-up (median 155 days), 11 (50%) received therapy directed to COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) of the patients survived, 15 (68%) were dialysis free, and eight (36%) achieved partial remission of proteinuria with residual CKD. Seven of the 14 patients who initially required dialysis came off dialysis. Despite the frequent reversibility of initial AKI, prognosis remains guarded, and more effective therapy is needed.

Background
The long-term outcome of COVID-19–associated collapsing glomerulopathy is unknown.

Methods
We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2.

Results
The 23 patients with COVID-19–associated collapsing glomerulopathy were median age 57 years (range, 35–72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30–412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected.

Conclusions
Half of 14 patients with COVID-19–associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.