Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy
Open accessAbstract
Background Acute kidney injury affects ~70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia.Methods Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis.Results Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia.Conclusion Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.
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Maternal creatine supplementation has been reported to improve neonatal survival and organ function following birth asphyxia in animals.
“Maternal creatine supplementation has been reported to improve neonatal survival and organ function following birth asphyxia in animals [228, 229, 231, 233–235, 237].”
From International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine (2017) · cites this paper as [228]
The Discussion reports that maternal creatine supplementation protected male spiny-mouse offspring from nephron loss and reduced kidney function after birth asphyxia. It does not report improved neonatal survival; a search for survival found only a general statement about sex differences in neonatal survival, not an effect of creatine. Page numbers were unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCreatine supplementation has been shown to improve brain and heart bioenergetics during ischemic conditions and possess neuroprotective properties.
“Since creatine supplementation has been shown to improve brain and heart bioenergetics during ischemic conditions and possess neuroprotective properties, there has been recent interest in use of creatine during pregnancy to promote neural development and reduce complications resulting from birth asphyxia [228–237].”
From International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine (2017) · cites this paper as [228]
The Discussion (page unavailable) says dietary creatine can prolong cellular energy homeostasis during severe hypoxia and hypoperfusion, and reports that maternal supplementation minimized neural injury in a spiny-mouse model of birth asphyxia. It does not specifically report improved brain and heart bioenergetics during ischemia; the study’s own measured outcomes concern kidney injury. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMaternal creatine supplementation has been reported to improve neonatal survival and organ function following birth asphyxia in animals.
“Maternal creatine supplementation has been reported to improve neonatal survival and organ function following birth asphyxia in animals [277,278,279,281,282,283,285].”
From Creatine in health and disease (2021) · cites this paper as [277]
Creatine supplementation has been shown to improve cellular bioenergetics during ischemic conditions and possess neuroprotective properties.
“Since creatine supplementation has been shown to improve cellular bioenergetics during ischemic conditions and possess neuroprotective properties, there has been interest in creatine use during pregnancy to promote neural development and reduce complications resulting from birth asphyxia [7,277,278,279,280,281,282,283,284,285].”
From Creatine in health and disease (2021) · cites this paper as [277]
Available literature suggests that creatine metabolism may play an essential role in the bioenergetics of successful reproduction and that creatine supplementation may improve reproductive and/or perinatal outcomes.
“Available literature suggests that creatine metabolism may play an essential role in the bioenergetics of successful reproduction and that creatine supplementation may improve reproductive and/or perinatal outcomes [7,277,278,279,280,283,284,286,288].”
From Creatine in health and disease (2021) · cites this paper as [277]
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Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-017-0173-z · Cited by 854 · see citing works
“Finally, creatine supplement has been used as a means of reducing homocysteine levels and/or improving patient outcomes in patients with renal disease [263–265] as well as ameliorating birth asphyxia related renal dysfunction in mice [228].”
MethodCreatine in health and disease
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Self-citation
- Authors
- Ellery, S. J., LaRosa, D. A., Cullen-McEwen, L. A., Brown, R. D., Snow, R. J., Walker, D. W., Kett, M. M., & Dickinson, H.
- Affiliations
- Monash Medical Centre (AU)
- Monash University (AU)
- Deakin University (AU)
- Corresponding author
- Ellery, Stacey J.
- Venue
- Pediatric Research
- Published
- 2016-12-20
- Volume
- 81
- Issue
- 4
- Pages
- 646-653
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2564711365
- Cited by
- 18
- References
- 42
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Monash University
- State Government of Victoria
- Hudson Institute of Medical Research
- Cerebral Palsy Alliance
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- neonatal asphyxia, acute kidney injury, chronic kidney disease, prenatal nutrition, nephron number, glomerular filtration rate, glomerulosclerosis, type IV collagen, spiny mouse, sex differences
- MeSH terms
- Animals, Animals, Newborn, Asphyxia Neonatorum, Creatine, Female, Kidney, Kidney Failure, Chronic, Kidney Glomerulus, Male, Nephrons, Organ Size, Oxygen, Pregnancy, Pregnancy, Animal, Dietary Supplements, Collagen Type IV, Maternal Nutritional Physiological Phenomena, Mice, Acute Kidney Injury
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