Abstract
Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life. This mini-review discusses critical developmental periods and long-term sequelae of renal programming in humans and presents studies examining the underlying mechanisms as well as interventional approaches to “re-program” renal susceptibility toward disease. Clinical manifestations of programmed kidney disease include arterial hypertension, proteinuria, aggravation of inflammatory glomerular disease, and loss of kidney function. Nephron number, regulation of the renin–angiotensin–aldosterone system, renal sodium transport, vasomotor and endothelial function, myogenic response, and tubuloglomerular feedback have been identified as being vulnerable to environmental factors. Oxidative stress levels, metabolic pathways, including insulin, leptin, steroids, and arachidonic acid, DNA methylation, and histone configuration may be significantly altered by adverse environmental conditions. Studies on re-programming interventions focused on dietary or anti-oxidative approaches so far. Further studies that broaden our understanding of renal programming mechanisms are needed to ultimately develop preventive strategies. Targeted re-programming interventions in animal models focusing on known mechanisms will contribute to new concepts which finally will have to be translated to human application. Early nutritional concepts with specific modifications in macro- or micronutrients are among the most promising approaches to improve future renal health.
Highlights
Prevention of chronic kidney disease is a major public health challenge [1]
Nephron number positively correlates with birth weight [53, 54] and is reduced after low-protein (LP) diet throughout pregnancy [55,56,57,58,59], utero-placental insufficiency angiotensin II infusion, adult LP offspring reacted with a greater decline in glomerular filtration rate (GFR) than controls [80]
Chronic kidney disease affects more than 10% of the population [1]
Summary
Diabetes mellitus is the most common cause of chronic kidney disease worldwide [2], developmental programming processes that have been reviewed by us [3, 4] and others [5,6,7] before substantially contribute to differences in morbidity and mortality between individuals. Adverse kidney programming increases the incidence of severe renal and cardiovascular sequels later in life. This includes arterial hypertension and associated end organ damage, the aggravation of inflammatory glomerular disease and the occurrence of end-stage renal disease. [3] Which environmental factors may have impact on kidney development and what are potential mechanisms of developmental kidney programming? (1) Which developmental stages are especially vulnerable? [2] What are the long-term sequelae of adverse renal programming? [3] Which environmental factors may have impact on kidney development and what are potential mechanisms of developmental kidney programming? [4] Whatarepotentialtherapeutic“re-programming”interventions?
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