Developmental Origins of Hypertension and Kidney Disease: Mechanisms of Nutritional Programming

Developmental origins of chronic diseases refers to prenatal “programming” by adverse intrauterine conditions which permanently alter fetal organ structure/function and homeostatic setpoints; this creates vulnerability to stressors in postnatal life and increases risk of developing chronic diseases such as hypertension, obesity, diabetes, heart disease, and certain cancers in later life. We now recognize that nutritional programming can result from not only fetal undernutrition, but also from overnutrition due to unbalanced high fat diets and/or maternal obesity. This presentation will focus on pathways by which undernutrition programs later-life hypertension, specifically via the interaction of impaired kidney development/nephron number, enhanced arterial reactivity to vasoconstrictive hormones, and altered regulation of appetite and energy utilization (the “thrifty phenotype”). An underlying theme is the idea the programming generates a “mismatch” between the functional capacity of an organ that is fixed at birth (eg the kidney, measured as nephron number) and the size of the load placed on it postnatally, where the body size can grow excessively and outstrip that organ capacity (ie waste or salt excretion load for the kidney). This leads to secondary compensatory responses (nephrons are forced to “overwork”) which maintain normal function on the short term but, on the long term, leads to both high blood pressure and enhanced risk of progressive chronic kidney disease. These pathways highlight the need for – and approaches to - systematic early identification of at-risk infants and children; they also suggest individual and policy-based interventions to modify adverse postnatal outcomes.