Effects of Klotho supplementation on hyperoxia-induced renal injury in a rodent model of postnatal nephrogenesis

Mohammed Farhan Ali, Sunil Kumar Bathally Venkatarayappa, Merline Benny, Claudia Rojas, Keyvan Yousefi, Lina A. Shehadeh, Shathiyah Kulandavelu, Mayank Sharma, Naimeh Da Silva, Michael Freundlich, Carolyn L. Abitbol, Marissa J. DeFreitas, Karen C. Young

Research output: Contribution to journalArticle

Abstract

Background: Hyperoxia (HO) causes kidney injury in preterm infants; however, whether these effects are modifiable is unknown. We hypothesized that administration of exogenous soluble Klotho, a kidney-derived antioxidant, would attenuate HO-induced kidney injury during postnatal nephrogenesis in rats. Methods: Sprague Dawley neonatal rats assigned to normoxia (21% O2) or HO (85% O2) groups from postnatal day (P) 1 to 21 were randomly assigned to receive alternate day intraperitoneal injections of recombinant Klotho or placebo for 3 weeks. They were recovered in normoxia for an additional 3 weeks and sacrificed at 6 weeks. Renal artery resistance and pulsatility indices, tubular injury scores, glomerular area, and renal antioxidant capacity were assessed. Results: Rodents exposed to HO during postnatal nephrogenesis had reduced kidney Klotho expression, glomerulomegaly, and higher tubular injury scores. Exogenous Klotho administration improved renal perfusion as indicated by decreases in both resistance and pulsatility indices and increased antioxidant enzyme expression. Conclusions: HO exposure during postnatal nephrogenesis in rodents results in a decline in kidney Klotho expression, decreased renal perfusion, enlarged glomerular size, and tubular injury. The exogenous administration of Klotho attenuated HO-induced kidney injury and augmented antioxidant capacity.

Original languageEnglish (US)
JournalPediatric Research
DOIs
StateAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Ali, M. F., Venkatarayappa, S. K. B., Benny, M., Rojas, C., Yousefi, K., Shehadeh, L. A., Kulandavelu, S., Sharma, M., Da Silva, N., Freundlich, M., Abitbol, C. L., DeFreitas, M. J., & Young, K. C. (Accepted/In press). Effects of Klotho supplementation on hyperoxia-induced renal injury in a rodent model of postnatal nephrogenesis. Pediatric Research. https://doi.org/10.1038/s41390-020-0803-z