Epidemiologic studies now strongly support the hypothesis, proposed over two decades ago, that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment and, based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size, and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and, conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt sensitivity, altered expression of renal sodium transporters, altered vascular reactivity, and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults, e.g. diabetes mellitus or rapid catch-up growth, leading to the vicious cycle of on-going hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, and hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate prenatal care and careful postnatal nutrition are crucial to optimize an individual’s nephron number during development and potentially to stem the tide of the growing cardiovascular and renal disease epidemics worldwide.

Two coding sequence variants in the gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.

intact animal to the cellular, subcellular, and molecular levels. It is published 12 times a year (monthly) by the American lymphatics, including experimental and theoretical studies of cardiovascular function at all levels of organization ranging from the publishes original investigations on the physiology of the heart, blood vessels, and AJP -Heart and Circulatory Physiology

No abstract