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

Ali, Mohammed Farhan; Venkatarayappa, Sunil Kumar Bathally; Benny, Merline; Rojas, Claudia; Yousefi, Keyvan; Kulandavelu, Shathiyah; Sharma, Mayank; Silva, Naimeh Da; Freundlich, Michael; Abitbol, Carolyn; DeFreitas, Marissa; Young, Karen

doi:10.1038/s41390-020-0803-z

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…Tain et al showed that ureteric bud branching morphogenesis was inhibited by asymmetric dimethylarginine (ADMA), a ROS inducer and endogenous NOS inhibitor, leading to decreased nephron number (55). However, some studies have not shown a decreased nephron number but rather glomerular hypertrophy (54,(57)(58)(59)(60) and tubulointerstitial injury (54,55,57,(59)(60)(61) as the renal phenotype associated with oxidative stress and perinatal programming. The main mechanisms of oxidative stress shown in these studies to be associated with renal injury include increased levels of asymmetric dimethylarginine (ADMA), F2 isoprostane, renal 8-hydroxydeoxyguanosine (8-OHdG) and MDA and decreased levels of NO and superoxide dismutase (62).…”

Section: Oxidative Stress and Programming Of Nephron Number And Kidne...mentioning

confidence: 99%

“…In the developing kidney, the negative impact of oxidative stress related to fluctuating oxygen exposure from hyperoxia to intermittent hypoxia, has also been implicated in the development of kidney injury in postnatal animal models (60,(73)(74)(75)(76)(77)(78) (Table 1). Nephrogenesis is complete by the 36th week of gestation in humans, but it continues until approximately postnatal day 10-14 in rats (73).…”

Section: Postnatal Oxidative Stress Induced Kidney Injury and Emergin...mentioning

confidence: 99%

“…CKD is a state of Klotho deficiency that exerts multiple systemic adverse effects, including the vascular system ( 86 – 89 ). Our group demonstrated in a rodent model of hyperoxia-induced kidney injury that hyperoxia exposure during early postnatal nephrogenesis was accompanied by a marked reduction of renal Klotho expression, restricted renal perfusion, and glomerulomegaly and tubular injury ( 60 ). Administration of exogenous Klotho improved renal vascular perfusion, abrogated glomerulomegaly and tubular injury, and restored kidney antioxidant capacity [manganese superoxide dismutase (MnSOD) and catalase mRNA expression] ( 60 ).…”

Section: Postnatal Oxidative Stress Induced Kidney Injury and Emergin...mentioning

confidence: 99%

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Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

et al. 2022

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Oxidative stress occurs when there is an imbalance between reactive oxygen species/reactive nitrogen species and antioxidant systems. The interplay between these complex processes is crucial for normal pregnancy and fetal development; however, when oxidative stress predominates, pregnancy related complications and adverse fetal programming such as preterm birth ensues. Understanding how oxidative stress negatively impacts outcomes for the maternal-fetal dyad has allowed for the exploration of antioxidant therapies to prevent and/or mitigate disease progression. In the developing kidney, the negative impact of oxidative stress has also been noted as it relates to the development of hypertension and kidney injury mostly in animal models. Clinical research addressing the implications of oxidative stress in the developing kidney is less developed than that of the neurodevelopmental and respiratory conditions of preterm infants and other vulnerable neonatal groups. Efforts to study the oxidative stress pathway along the continuum of the perinatal period using a team science approach can help to understand the multi-organ dysfunction that the maternal-fetal dyad sustains and guide the investigation of antioxidant therapies to ameliorate the global toxicity. This educational review will provide a comprehensive and multidisciplinary perspective on the impact of oxidative stress during the perinatal period in the development of maternal and fetal/neonatal complications, and implications on developmental programming of accelerated aging and cardiovascular and renal disease for a lifetime.

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Section: Oxidative Stress and Programming Of Nephron Number And Kidne...mentioning

confidence: 99%

Section: Postnatal Oxidative Stress Induced Kidney Injury and Emergin...mentioning

confidence: 99%

Section: Postnatal Oxidative Stress Induced Kidney Injury and Emergin...mentioning

confidence: 99%

See 1 more Smart Citation

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

et al. 2022

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“…Additionally, in rodents, exposure to hyperoxia during early nephrogenesis in the postnatal period was accompanied by a significant reduction in the expression of renal klotho. 39 Hyperoxia-induced acute kidney injury (AKI) has also been studied in two phases, with the early phase associated with the inhibition of kidney growth and the activation of IL-6 and Smad2 signaling. During the second phase, catch-up growth, as well as impaired glomerular and tubular function, occurs, and the IL-6/Smad2 signaling axis mediates AKI and regeneration in a hyperoxic mouse model, increasing the risk of CKD in adulthood.…”

Section: The Mechanism Of Hyperoxia-induced Neonatal Renal Injurymentioning

confidence: 99%

The Mechanism of Hyperoxia-Induced Neonatal Renal Injury and the Possible Protective Effect of Resveratrol

2022

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With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless,epidemiological data on the health status of these preterm infants has begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in in adulthood, affecting their quality-of-life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and the hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury.

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“…We recently studied the effects of Klotho administration in rodents with hyperoxia-induced pulmonary and kidney damage. The rodents displayed reduced kidney Klotho expression, glomerulomegaly, and tubular injury, and exogenous Klotho administration improved kidney perfusion, increased intrarenal antioxidant capacity, and reduced kidney injury [141]. There was also improved lung vascular development, attenuated vascular remodeling, and reduced pulmonary hypertension and cardiac biventricular hypertrophy [142].…”

Section: Klotho Reactivation and Exogenous Administrationmentioning

confidence: 99%

Fibroblast growth factor 23—Klotho and hypertension: experimental and clinical mechanisms

2020

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Hypertension (HTN) and chronic kidney disease (CKD) are increasingly recognized in pediatric patients and represent risk factors for cardiovascular morbidity and mortality later in life. In CKD, enhanced tubular sodium reabsorption is a leading cause of HTN due to augmented extracellular fluid volume expansion. The renin-angiotensin-aldosterone system (RAAS) upregulates various tubular sodium cotransporters that are also targets of the hormone fibroblast growth factor 23 (FGF23) and its co-receptor Klotho. FGF23 inhibits the activation of 1,25-dihydroxyvitamin D that is a potent suppressor of renin biosynthesis. Here we review the complex interactions and disturbances of the FGF23-Klotho axis, vitamin D, and the RAAS relevant to blood pressure regulation and discuss the therapeutic strategies aimed at mitigating their pathophysiologic contributions to HTN.

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

Cited by 13 publications

References 39 publications

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

The Mechanism of Hyperoxia-Induced Neonatal Renal Injury and the Possible Protective Effect of Resveratrol

Fibroblast growth factor 23—Klotho and hypertension: experimental and clinical mechanisms

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