Early-Life Programming and Reprogramming of Adult Kidney Disease and Hypertension: The Interplay between Maternal Nutrition and Oxidative Stress

Abstract

Kidney disease and hypertension both have attained the status of a global pandemic. Altered renal programming resulting in kidney disease and hypertension can begin in utero. Maternal suboptimal nutrition and oxidative stress have important implications in renal programming, while specific antioxidant nutrient supplementations may serve as reprogramming strategies to prevent kidney disease and hypertension of developmental origins. This review aims to summarize current knowledge on the interplay of maternal nutrition and oxidative stress in response to early-life insults and its impact on developmental programming of kidney disease and hypertension, covering two aspects. Firstly, we present the evidence from animal models supporting the implication of oxidative stress on adult kidney disease and hypertension programmed by suboptimal maternal nutrition. In the second part, we document data on specific antioxidant nutrients as reprogramming strategies to protect adult offspring against kidney disease and hypertension from developmental origins. Research into the prevention of kidney disease and hypertension that begin early in life will have profound implications for future health.

Keywords: antioxidant; developmental origins of health and disease (DOHaD); hydrogen sulfide; hypertension; kidney disease; nitric oxide; nutrition; offspring; oxidative stress; pregnancy; reprogramming.

Figure 1

Schematic illustration of the association between maternal nutrition, oxidative stress, renal programming, and increased vulnerability to kidney disease and hypertension in adult offspring. Red arrow indicates imbalanced nutrients in pregnancy and lactation causes oxidative stress and renal programming, consequently leading to kidney disease and hypertension in adult offspring. There are several signaling systems for maintaining the redox balance, including reactive oxygen species (ROS), reactive nitrogen species (RNS), nitric oxide (NO), and hydrogen sulfide (H₂S). Conversely, certain antioxidant nutrients can serve as reprogramming strategies to reverse the programmed processes and prevent the developmental programming of kidney disease and hypertension, which is indicated by blue arrow and lines.

Figure 2

Schematic representation of the interrelationships between reactive oxygen species (ROS, antioxidant defense system, nitric oxide (NO), and hydrogen sulfide (H₂S) signaling system in the kidney to control blood pressure and renal function. Imbalanced nutrition can activate reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to kidney damage and vasoconstriction. Several oxidative enzymes can produce superoxide anion (O2⁻), such as NADPH oxidase, xanthine oxidase, and mitochondrial respiration. The superoxide anion can interact with nitric oxide (NO) to form peroxynitrite (ONOO⁻). Hydrogen peroxide (H₂O₂) and hydroxyl anion (OH⁻) are reactive byproducts of superoxide. These ROS can be produced via superoxide dismutase (SOD), catalase, or glutathione peroxidase (GPx). On the other hand, dietary nutrients provide L-arginine and L-methionine for the synthesis of NO and H₂S, respectively. Both NO and H₂S are vasodilators and play a key role in maintaining renal physiology. While L-arginine can also be posttranslational methylation to form asymmetric or symmetric dimethylarginine (ADMA or SDMA), both are endogenous inhibitors of nitric oxide synthase (NOS). There is a relationship between the L-arginine-NO and the H₂S-synthesizing pathway. The protein arginine methyltransferases (PRMTs) methylate L-arginine to generate ADMA/SDMA and concurrently demethylate methionine to form homocysteine. S-adenosylmethionine (SAM) is used as a substrate for methyl transfers that yield S-adenosylhomocysteine (SAH). Homocysteine can further be broken down to generate L-cysteine and glutathione.