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.
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Acknowledgements
This work was supported by grant funding from the Batchelor Children’s Research Awards to C.L.A. and K.C.Y. L.A.S. is funded by grants from the NIH (1R01HL140468) and the Miami Heart Research Institute. K.Y. is a recipient of AHA predoctoral fellowship (18PRE33960070).
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All authors provided substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data. M.F.A., S.K.B.V., M.B., S.K., M.F., C.L.A., M.J.D., and K.C.Y. contributed to the drafting of the article and/or critical revision for important intellectual content, and all authors approved the final version of the submitted manuscript.
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Ali, M.F., Venkatarayappa, S.K.B., Benny, M. et al. Effects of Klotho supplementation on hyperoxia-induced renal injury in a rodent model of postnatal nephrogenesis. Pediatr Res 88, 565–570 (2020). https://doi.org/10.1038/s41390-020-0803-z
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DOI: https://doi.org/10.1038/s41390-020-0803-z
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