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The kidney injury caused by the onset of acute graft-versus-host disease is associated with down-regulation of αKlotho
Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
Karolinska Univ Hosp, Novum, Clin Res Ctr, Huddinge, Sweden.
Karolinska Inst, Novum, Clin Res Ctr, Expt Canc Med, S-14186 Stockholm, Sweden.
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2020 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 78, article id 106042Article in journal (Refereed) Published
Abstract [en]

Acute graft-versus-host disease (aGVHD) and kidney injury are the major complications after allogeneic hematopoietic stem cell transplantation (HSCT). Although the underlying mechanisms for the development of these complications are not yet fully understood, it has been proposed that emergence of aGVHD contributes to the development of kidney injury after HSCT. We have shown previously that aGVHD targets the kidney in a biphasic manner: at the onset, inflammatory genes are up-regulated, while when aGVHD becomes established, donor lymphocytes infiltrate the kidney. Here, we characterize renal manifestations at the onset of aGVHD. Mice receiving allogeneic bone marrow and spleen cells displayed symptoms of aGVHD and elevated serum levels of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) within 4 days. There was concurrent kidney injury with the following characteristics: (1) elevated expression of the kidney injury biomarker, neutrophil gelatinase-associated lipocalin (NGAL), (2) accumulation of hetero-lysosomes in proximal tubule epithelial cells, and (3) reductions in αKlotho mRNA and protein and increased serum levels of fibroblast growth factor 23 (Fgf23), phosphate and urea. This situation resembled acute renal injury caused by bacterial lipopolysaccharide. We conclude that the onset of aGVHD is associated with kidney injury involving down-regulation of αKlotho, a sight that may inspire novel therapeutic approaches.

Place, publisher, year, edition, pages
2020. Vol. 78, article id 106042
Keywords [en]
Acute graft versus host disease, Fibroblast growth factor 23, alpha Klotho, Hematopoietic stem cell transplantation, Interferon gamma, Kidney injury, Lysosome, Tumor necrosis factor alpha
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-407452DOI: 10.1016/j.intimp.2019.106042ISI: 000510086800002PubMedID: 31812067OAI: oai:DiVA.org:uu-407452DiVA, id: diva2:1416713
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research The Cancer Research Funds of Radiumhemmet, 161082Swedish Childhood Cancer Foundation, PR2017-0083The Karolinska Institutet's Research Foundation, 2018-02377Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-25Bibliographically approved

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Burmakin, Mikhail

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