{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:03Z","timestamp":1786480323345,"version":"build-2736575974"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["RO1 DK133401"],"award-info":[{"award-number":["RO1 DK133401"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["RO1 DK133401"],"award-info":[{"award-number":["RO1 DK133401"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n \n Understanding how heme proteins\/heme induce AKI and whether NAD\n +<\/jats:sup>\n -boosting ameliorates heme protein\u2013mediated AKI is clinically relevant.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Heme proteins\/heme directly decrease kidney NAD\n +<\/jats:sup>\n content and NAD\n +<\/jats:sup>\n -boosting is markedly protective in heme protein\u2013mediated AKI.\n <\/jats:p>\n <\/jats:list-item>\n \n \n These findings provide new insights in heme protein\u2013mediated AKI and support interest in NAD\n +<\/jats:sup>\n -boosting as a therapeutic strategy in AKI.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Understanding how heme proteins and heme induce AKI is clinically relevant from numerous perspectives, and, in this regard, a widely used model of heme protein\u2013mediated AKI (HP-AKI) involves the glycerol model in mice. Using this model, we have previously demonstrated that NAD\n +<\/jats:sup>\n content is decreased in HP-AKI. Because there is significant current interest in NAD\n +<\/jats:sup>\n -boosting as a strategy in clinical AKI, we examined the effect of NAD\n +<\/jats:sup>\n -boosting in this model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n NAD\n +<\/jats:sup>\n -boosting was achieved by the administration of nicotinamide mononucleotide (NMN) in the glycerol model of HP-AKI. The effect of NMN, compared with vehicle, was examined in mice with HP-AKI and with sham AKI at day 1 after HP-AKI was induced.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The administration of NMN preserved kidney NAD\n +<\/jats:sup>\n content in HP-AKI, and compared with the administration of vehicle in HP-AKI, NMN improved glomerular filtration markers; reduced histologic injury as assessed by tubular necrosis, dilation, and cast formation and by assessment of dystrophic calcification; reduced expression of kidney injury marker 1, a sensitive marker of AKI; preserved mitochondrial ultrastructure and increased expression of proteins that promote mitochondrial integrity; reduced apoptosis as assessed by terminal deoxynucleotidyl transferase\u2013mediated digoxigenin-deoxyuridine nick-end labeling staining and genes and protein expression that contribute to apoptosis, while increasing expression of an anti-apoptotic gene; reduced expression of several renal injury-related genes; and mitigated the severity of the senescence phenotype, as assessed by multiple markers. Finally, the administration of myoglobin or heme\n in vivo<\/jats:italic>\n diminished kidney NAD\n +<\/jats:sup>\n content in mice with intact kidneys.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings demonstrate the remarkable protective effects of NAD\n +<\/jats:sup>\n -boosting by NMN in HP-AKI as revealed by a multitude of markers relevant to AKI. The reduction in NAD\n +<\/jats:sup>\n content in the kidney in HP-AKI may reflect the direct effects of heme proteins and\/or heme. We suggest that these findings support current interest in NAD\n +<\/jats:sup>\n -boosting as a therapeutic strategy in clinical AKI.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001032","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T17:00:23Z","timestamp":1764090023000},"page":"475-486","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["NAD+-Boosting Ameliorates Heme Protein\u2013Mediated Acute Kidney Injury"],"prefix":"10.34067","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-2722","authenticated-orcid":false,"given":"Raman Deep","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Croatt","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5674-1682","authenticated-orcid":false,"given":"Joseph P.","family":"Grande","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan W.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-6259","authenticated-orcid":false,"given":"Trace A.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Microscopy and Cell Analysis Core Facility, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-2747","authenticated-orcid":false,"given":"Luis A.","family":"Juncos","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas"},{"name":"Medical Affairs, FME Global Medical Office Waltham, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-5506","authenticated-orcid":false,"given":"Karl A.","family":"Nath","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"1","key":"B1-20260330","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra0801327","article-title":"Rhabdomyolysis and acute 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