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Genetic Kidney Diseases of Childhood

Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2018.00036

Developmental Programming of Renal Function and Re-programming Approaches

Eva Nüsken1, Jörg Dötsch1,  Lutz T. Weber1 and  Kai D. Nüsken1*
  • 1Department of Pediatrics, Medizinische Fakultät, Universität zu Köln, Germany

Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors 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 towards 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.

Keywords: kidney development, nephron number, Renin-angiotensin-aldosterone-system, renal sodium transport, Blood Pressure, myogenic response, tubuloglomerular feedback, early nutrition, re-programming intervention

Received: 20 Oct 2017; Accepted: 08 Feb 2018.

Edited by:

Miriam Schmidts, Radboud University Nijmegen, Netherlands

Reviewed by:

Jan M. Williams, University of Mississippi Medical Center School of Dentistry, United States
Larry T. Patterson, Children’s National Health System, United States  

Copyright: © 2018 Nüsken, Dötsch, Weber and Nüsken. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Kai D. Nüsken, Medizinische Fakultät, Universität zu Köln, Department of Pediatrics, Cologne, 50937, Germany, kai-dietrich.nuesken@uk-koeln.de