TY - JOUR
T1 - Effects of Klotho supplementation on hyperoxia-induced renal injury in a rodent model of postnatal nephrogenesis
AU - Ali, Mohammed Farhan
AU - Venkatarayappa, Sunil Kumar Bathally
AU - Benny, Merline
AU - Rojas, Claudia
AU - Yousefi, Keyvan
AU - Shehadeh, Lina A.
AU - Kulandavelu, Shathiyah
AU - Sharma, Mayank
AU - Da Silva, Naimeh
AU - Freundlich, Michael
AU - Abitbol, Carolyn L.
AU - DeFreitas, Marissa J.
AU - Young, Karen C.
N1 - Funding Information:
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).
Publisher Copyright:
© 2020, International Pediatric Research Foundation, Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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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U2 - 10.1038/s41390-020-0803-z
DO - 10.1038/s41390-020-0803-z
M3 - Article
C2 - 32059229
AN - SCOPUS:85079719542
VL - 88
SP - 565
EP - 570
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 4
ER -