Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring DOI Creative Commons
Jessica F. Hebert, Y. Funahashi, Jacqueline Emathinger

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Introduction: Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As influences developmental programming, we hypothesized that recovered parental results poor outcomes, impaired fetal growth, adult offspring disease. Methods: Using well-characterized model of rhabdomyolysis-induced acute (RIAKI), form commonly observed young people, confirmed functional renal recovery by assessing glomerular filtration rate (GFR) 2 weeks following RIAKI. We bred sham RIAKI sires dams timed, matched matings for gestational day (GD) 16.5 (birth–12 weeks, 6 months) study. Results: Despite normal GFR pre-pregnancy, at GD16.5 had function, resulting reduced fetoplacental ratios survival. Pregnant also albuminuria less megalin the proximal tubule brush border than shams, subcapsular fibrosis higher diastolic blood pressure. Growth-restricted as older adults, evidence metabolic inefficiency male offspring; this correlated AngII levels female from pairings. However, pressures 6-month-old were unaffected Conclusions: Our mouse demonstrated causal relationship among RIAKI, risk, programming adult-onset dysregulation despite recovery.

Language: Английский

Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury DOI Creative Commons
Y. Funahashi, Seung Hun Park, Jessica F. Hebert

et al.

Kidney International, Journal Year: 2024, Volume and Issue: 106(4), P. 597 - 610

Published: July 26, 2024

Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense care, and early chronic disease. AKI often follows an acute event such that timely treatment could ameliorate potentially reduce additional Despite therapeutic success dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve safety efficacy for AKI, we developed characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting proximal tubular epithelial cells provided by megalin ligand cilastatin. Cilastatin were complexed H-Dot nanoparticles, which constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics found be stable at plasma pH salutary release kinetics urine pH. In vivo, they specifically biodistributed bladder, with 75% recovery reduced systemic toxicity compared native dexamethasone. complexation conferred cell specificity within vivo enabled delivery nucleus vitro. The nanotherapeutic improved function cellular when administered male C57BL/6 mice two translational models (rhabdomyolysis bilateral ischemia reperfusion). Thus, our design-based loading resulted preservation dexamethasone, combined off-target disposition toxic effects. Hence, study illustrates potential strategy target other diseases kidney.

Language: Английский

Citations

5
Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring DOI Creative Commons
Jessica F. Hebert, Y. Funahashi, Jacqueline Emathinger

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Introduction: Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As influences developmental programming, we hypothesized that recovered parental results poor outcomes, impaired fetal growth, adult offspring disease. Methods: Using well-characterized model of rhabdomyolysis-induced acute (RIAKI), form commonly observed young people, confirmed functional renal recovery by assessing glomerular filtration rate (GFR) 2 weeks following RIAKI. We bred sham RIAKI sires dams timed, matched matings for gestational day (GD) 16.5 (birth–12 weeks, 6 months) study. Results: Despite normal GFR pre-pregnancy, at GD16.5 had function, resulting reduced fetoplacental ratios survival. Pregnant also albuminuria less megalin the proximal tubule brush border than shams, subcapsular fibrosis higher diastolic blood pressure. Growth-restricted as older adults, evidence metabolic inefficiency male offspring; this correlated AngII levels female from pairings. However, pressures 6-month-old were unaffected Conclusions: Our mouse demonstrated causal relationship among RIAKI, risk, programming adult-onset dysregulation despite recovery.

Language: Английский

Citations

0