TY - JOUR
T1 - Characteristics and Outcomes of NELL1 Membranous Nephropathy in Lipoic Acid Users and Nonusers
AU - Avasare, Rupali S.
AU - Clark, Samantha
AU - Spain, Rebecca I.
AU - Wusirika, Raghav
AU - Rope, Robert
AU - Gurley, Susan
AU - Stanaway, Madison
AU - Sekulic, Miroslav
AU - Santoriello, Dominick
AU - Bomback, Andrew S.
AU - Canetta, Pietro
AU - Iyer, Sitalakshmi J.
AU - Kung, Vanderlene
AU - Charu, Vivek
AU - Troxell, Megan L.
AU - Kudose, Satoru
AU - Andeen, Nicole K.
N1 - Publisher Copyright:
© 2024 International Society of Nephrology
PY - 2024/5
Y1 - 2024/5
N2 - Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome. Methods: We retrospectively reviewed clinicopathologic features of NELL1 MN from 3 institutions and analyzed clinical and histologic associations with outcome. Results: Of 70 patients, 53% were male with a median age of 66 years; median proteinuria was 5.9 g/d. NELL1 MN was associated with lipoic acid (36%), heavy nonsteroidal antiinflammatory drug (NSAID) use (27%), autoimmune disease (23%), malignancy (10% recent, 23% any), mercury exposure (1%), and 11% had no known secondary association. At median follow-up of 11 months, 72% achieved complete or partial remission. Remission rate was 91% in patients with lipoic acid-associated NELL1 MN and ≥6 months of follow-up. On multivariable analyses, patients with primary NELL1 MN (adjusted odds ratio [OR]: 19.7, P = 0.01) and increasing degree of tubular atrophy and interstitial fibrosis (IFTA) (adjusted OR 1.1, P = 0.01) were less likely to achieve any remission, whereas complete remission (CR) was associated with lipoic acid use (adjusted OR: 10.9, P = 0.04, 95% confidence interval [CI]: 1.2–100) and lesser degrees of IFTA (adjusted OR: 0.79, P = 0.16, 95% CI: 0.66–0.96). Conclusion: Our findings strengthen the association between lipoic acid and NELL1 MN. Furthermore, our findings suggest that discontinuation of lipoic acid without immunosuppression should be considered as the first-line treatment.
AB - Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome. Methods: We retrospectively reviewed clinicopathologic features of NELL1 MN from 3 institutions and analyzed clinical and histologic associations with outcome. Results: Of 70 patients, 53% were male with a median age of 66 years; median proteinuria was 5.9 g/d. NELL1 MN was associated with lipoic acid (36%), heavy nonsteroidal antiinflammatory drug (NSAID) use (27%), autoimmune disease (23%), malignancy (10% recent, 23% any), mercury exposure (1%), and 11% had no known secondary association. At median follow-up of 11 months, 72% achieved complete or partial remission. Remission rate was 91% in patients with lipoic acid-associated NELL1 MN and ≥6 months of follow-up. On multivariable analyses, patients with primary NELL1 MN (adjusted odds ratio [OR]: 19.7, P = 0.01) and increasing degree of tubular atrophy and interstitial fibrosis (IFTA) (adjusted OR 1.1, P = 0.01) were less likely to achieve any remission, whereas complete remission (CR) was associated with lipoic acid use (adjusted OR: 10.9, P = 0.04, 95% confidence interval [CI]: 1.2–100) and lesser degrees of IFTA (adjusted OR: 0.79, P = 0.16, 95% CI: 0.66–0.96). Conclusion: Our findings strengthen the association between lipoic acid and NELL1 MN. Furthermore, our findings suggest that discontinuation of lipoic acid without immunosuppression should be considered as the first-line treatment.
KW - NELL1
KW - NSAID
KW - drug-induced kidney disease
KW - glomerular disease
KW - lipoic acid
KW - membranous nephropathy
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U2 - 10.1016/j.ekir.2024.02.1401
DO - 10.1016/j.ekir.2024.02.1401
M3 - Article
AN - SCOPUS:85187704263
SN - 2468-0249
VL - 9
SP - 1379
EP - 1386
JO - Kidney International Reports
JF - Kidney International Reports
IS - 5
ER -