Programming of Renal Development and Chronic Disease in Adult Life

Abstract

Chronic kidney disease (CKD) can have an insidious onset because there is a gradual decline in nephron number throughout life. There may be no overt symptoms of renal dysfunction until about two thirds or more of the nephrons have been destroyed and glomerular filtration rate (GFR) falls to below 25% of normal (often in mid-late life) ( Martinez-Maldonaldo et al., 1992 ). Once End Stage Renal Disease (ESRD) has been reached, survival depends on renal replacement therapy (RRT). CKD causes hypertension and cardiovascular disease; and hypertension causes CKD. Albuminuria is also a risk factor for cardiovascular disease. The age of onset of CKD is partly determined during fetal life. This review describes the mechanisms underlying the development of CKD in adult life that results from abnormal renal development caused by an adverse intrauterine environment. The basis of this form of CKD is thought to be mainly due to a reduction in the number of nephrons formed in utero which impacts on the age dependent decline in glomerular function. Factors that affect the risk of reduced nephron formation during intrauterine life are discussed and include maternal nutrition (malnutrition and obesity, micronutrients), smoking and alcohol, use of drugs that block the maternal renin-angiotensin system, glucocorticoid excess and maternal renal dysfunction and prematurity. Since CKD, hypertension and cardiovascular disease add to the disease burden in the community we recommend that kidney size at birth should be recorded using ultrasound and those individuals who are born premature or who have small kidneys at this time should be monitored regularly by determining GFR and albumin:creatinine clearance ratio. Furthermore, public health measures aimed at limiting the prevalence of obesity and diabetes mellitus as well as providing advice on limiting the amount of protein ingested during a single meal, because they are all associated with increased glomerular hyperfiltration and subsequent glomerulosclerosis would be beneficial.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats

“…The HDAC activity measurement kit (K331) was purchased from BioVision (Milpitas, CA, USA). Ouabain (O3125), furosemide (F4381), histone type III-S (H5505), and PKAi (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) peptide (P7739) were purchased from Sigma-Aldrich (Saint Louis, MO, USA). Calphostin C (208725) was purchased from Calbiochem (San Diego, CA, USA).…”

“…The risk of prevalent morbidities aggravated by malnutrition, such as kidney and cardiovascular diseases, are frequently associated with alterations in the renin-angiotensin-aldosterone system (RAAS) [1][2][3]. In the last few decades, several studies tried to elucidate the mechanisms by which malnutrition-induced systemic and local RAAS upregulation -in different windows of development -alters renal and cardiac Na + metabolism, leading to diseases such as arterial hypertension and cardiorenal syndrome [4][5][6][7][8][9][10][11][12]. We have demonstrated that renal and cardiac Na + handling is compromised by chronic multifactorial malnutrition due to upregulation of the AT 1 R → PKC signaling pathway [8,9], culminating in the onset of arterial hypertension [8]; the effects resulting from RAAS activation were blocked by Losartan (Los), an antagonist of the type 1 angiotensin II (Ang II) receptors (AT 1 R), thus confirming the role of RAAS in the pathophysiology of malnutrition-induced renal and cardiovascular lesions.…”

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response, Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice

“…While previous studies have demonstrated that maternal obesity has a detrimental impact on the development of the cardiovascular, pulmonary, and renal system with subsequent risk for chronic diseases later in life, the impact of maternal obesity on liver development and liver growth remains elusive [ 11 , 12 ]. The liver acts as the central regulator of energy homeostasis by orchestrating numerous metabolic processes, e.g., glycolysis, gluconeogenesis, and fatty acid metabolism.…”

Cohort profile: the Taicang and Wuqiang mother–child cohort study (TAWS) in China

“…Evidence from epidemiological studies and animal models has bolstered the paradigm of ‘developmental origins of health and disease’ over the past decades 1–4. It is now well established that the first 1000 days of life (ie, from conception to the age of 2 years) is a critical time window for developmental trajectory programming 5 6. Adverse disturbances that occurred during this period may lead to increased risks of chronic diseases across one’s lifespan or an epigenetic transgenerational inheritance of such risks 7–10.…”