From secondary to primary prevention of progressive renal disease: The case for screening for albuminuria

From secondary to primary prevention of progressive renal disease: The case for screening for albuminuria. Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended to primary prevention for those subjects in the general population who are at risk for progressive renal failure, but who had never suffered from a primary renal disease. We show that such subjects can be detected by screening for albuminuria. Elevated urinary albumin loss is an indicator not only of poor renal, but also of poor cardiovascular prognosis. In addition to diabetic subjects who are at risk for albuminuria, we also show that hypertensive, obese, and smoking subjects are more susceptible. We suggest that therapies that have been shown to lower albumin excretion, such as ACE inhibitors, angiotensin II receptor antagonists, and statins be started early in such patients to prevent them from developing clinical renal disease and its attendant cardiovascular complications

Low Nephron Number and Its Clinical Consequences

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

Climate change and its influence in nephron mass

PURPOSE OF REVIEW The consequences of climate change, including heat and extreme weather events impact kidney function in adults and children. The impacts of climate change on kidney development during gestation and thereby on kidney function later in life have been poorly described. Clinical evidence is summarized to highlight possible associations between climate change and nephron mass. RECENT FINDINGS Pregnant women are vulnerable to the effects of climate change, being less able to thermoregulate, more sensitive to the effects of dehydration, and more susceptible to infections. Exposure to heat, wildfire smoke, drought, floods and climate-related infections are associated with low birth weight, preterm birth and preeclampsia. These factors are associated with reduced nephron numbers, kidney dysfunction and higher blood pressures in offspring in later life. Exposure to air pollution is associated with higher blood pressures in children and has variable effects on estimated glomerular filtration rate. SUMMARY Climate change has important impacts on pregnant women and their unborn children. Being born too small or too soon is associated with life-time risk of kidney disease. Climate change may therefore have a dual effect of impacting fetal kidney development and contributing to cumulative postnatal kidney injury. The impact on population kidney health of future generations may be significant

Dynamics of glomerular ultrafiltration: VI. Studies in the primate

Dynamics of glomerular ultrafiltration: VI. Studies in the primate. Pressures and flows were measured in accessible surface glomeruli of the squirrel monkey under conditions of normal hydropenia. Mean glomerular capillary hydrostatic pressure and the mean glomerular transcapillary hydrostatic pressure difference (ΔP) averaged approximately 45 mm Hg and 35 mm Hg, respectively. These findings are in close accord with recent direct estimates in the rat. The net driving force for ultrafiltration was found to decline from a maximum value of about 12 mm Hg at the afferent end of the glomerular capillary network essentially to zero by the efferent end, indicating that, in the monkey as in the rat, filtration pressure equilibrium is achieved under normal hydropenic conditions. The monkey differs from the rat in one important respect, however, in that, as has long been recognized, the monkey tends to have higher systemic total plasma protein concentrations (CA) than the rat. This is of interest since monkey, like man, is found to have lower filtration fractions than the rat. Since ΔP is found to be essentially similar in monkey and rat, and since, at filtration pressure equilibrium, filtration fraction is determined by ΔP and CA, these observed differences in filtration fraction between rodent and primate must therefore be due to these differences in CA