TY - JOUR
T1 - Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury
T2 - An Observational Study
AU - Raines, Nathan H.
AU - Ganatra, Sarju
AU - Nissaisorakarn, Pitchaphon
AU - Pandit, Amar
AU - Morales, Alex
AU - Asnani, Aarti
AU - Sadrolashrafi, Mehrnaz
AU - Maheshwari, Rahul
AU - Patel, Rushin
AU - Bang, Vigyan
AU - Shreyder, Katherine
AU - Brar, Simarjeet
AU - Singh, Amitoj
AU - Dani, Sourbha S.
AU - Knapp, Sarah
AU - Poyan Mehr, Ali
AU - Brown, Robert S.
AU - Zeidel, Mark L.
AU - Bhargava, Rhea
AU - Schlondorff, Johannes
AU - Steinman, Theodore I.
AU - Mukamal, Kenneth J.
AU - Parikh, Samir M.
N1 - Funding Information:
A. Asnani reports being a scientific advisor or members of Sarnoff Cardiovascular Research Foundation, and receiving honoraria from UpToDate. R.S. Brown received royalties from Börm Bruckmeier Publishing LLC for a book and two applications, Nephrology Pocket and Acid Base and Electrolytes, on smartphones, with the second edition of Nephrology Pocket to be published by Elsevier, Inc. In R.S. Brown’s role at Harvard Medical Faculty Physicians (HMFP) at Beth Israel Deaconess Medical Center, he serves as an associate medical director of DaVita Dialysis Center (Brookline, MA). All income paid by this facility goes directly to HMFP, from which he receives a fixed salary. He also reports receiving honoraria from Harvard Medical School Department of Continuing Education, Beth Israel Deaconess Medical Center; having ownership interest in Innovative Wellness Systems, Inc.; being a member of the medical advisory board of the National Kidney Foundation of New England; and being on the board of directors and president of The Organization for Renal Care in Haiti (TORCH) Inc., a nonprofit, charitable corporation in Massachusetts. No income is received from any of these entities. K. Mukamal reports having other interests/relationships with US Highbush Blueberry Council and Wolters Kluwer. S.M. Parikh is listed as an inventor on patent filings from Beth Israel Deaconess Medical Center related to NAD+. S.M. Parikh reports having consultancy agreements with Aerpio, Alkermes, Astellas, Cytokinetics, Hope Pharmaceuticals, Janssen, Leerink Swann, Mission Therapeutics, and Mitobridge; being a scientific advisor for or member of Aerpio, JASN, Kidney360, and Raksana; receiving consulting fees in the last 3 years from Alkermes, Astellas, Cytokinetics, Daiichi Sankyo, Janssen, and Mission Therapeutics; receiving honoraria from American Society of Nephrology; receiving research funding from Baxter; and having ownership interest in Eunoia and Raksana. Work in S.M. Parikh’s laboratory is supported by National Heart, Lung, and Blood Institute grant R35-HL139424, National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK095072, and National Institute on Aging grant R01-AG027002. A. Poyan Mehr reports receiving research funding from ASN Carl W. Gottschalk Research Scholar Grant (2018) and Retrophin; being the site principle investigator for the DUPLEX Study (a phase-3 randomized trial in primary FSGS); having industry-sponsored clinical trial agreements with OMEROS, Roche, and Vertex; being the director of the GlomCon Project, an initiative to enhance education about glomerular disorders. This project is collaborating closely with the NephCure Foundation, which has provided financial and in-kind support for a continuing medical education–accredited conference series focused on clinical trials. A. Poyan Mehr has additional educational collaborations with the Renal Pathology Society and the European Renal Association. A. Poyan Mehr’s employer does not permit serving on any speaker bureau, advisory board, perform consultancy, or receive industry honoraria. N.H. Raines reports being a scientific advisor for or member of La Isla Network. J. Schlondorff reports being a scientific advisor for or member of the Alport Syndrome Foundation Medical Advisory Committee and having patents and inventions with Partners Healthcare. T.I. Steinman reports being a reviewer for CJASN and a member of the editorial board for Nephrology News and Issues; receiving research funding from Kadmon, Reata, and Retrophin; receiving honoraria from Mallinkrodt and Otsuka; being on the medical advisory board for the National Kidney Foundation of Massachusetts, Rhode Island, New Hampshire, and Vermont; and having other interests/relationships with National Kidney Foundation and Polycystic Kidney Foundation. M.L. Zeidel reports being a scientific advisor for or member of the Beth Israel Deaconess Medical Center and Hebrew Senior Life. All remaining authors have nothing to disclose.
Funding Information:
N.H. Raines is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant T32-DK007199.
Publisher Copyright:
Copyright © 2021 by the American Society of Nephrology.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Background AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m 2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P0.03; P interaction with KDIGO stage0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction0.03). Conclusions Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.
AB - Background AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m 2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P0.03; P interaction with KDIGO stage0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction0.03). Conclusions Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.
KW - COVID-19
KW - NAD+
KW - SARS-CoV-2
KW - acute kidney injury
KW - acute kidney injury and ICU nephrology
KW - acute renal failure
KW - clinical trial
KW - niacinamide
KW - outcomes
KW - vitamin B3
UR - http://www.scopus.com/inward/record.url?scp=85119443905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119443905&partnerID=8YFLogxK
U2 - 10.34067/KID.0006452020
DO - 10.34067/KID.0006452020
M3 - Article
C2 - 35368823
AN - SCOPUS:85119443905
SN - 2641-7650
VL - 2
SP - 33
EP - 41
JO - Kidney360
JF - Kidney360
IS - 1
ER -