Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone.

Dietary alkali slows GFR decline in humans with a moderately reduced glomerular filtration rate (GFR) despite the absence of metabolic acidosis. Similarly, dietary alkali slows GFR decline in animals with 2/3 nephrectomy (Nx), a chronic kidney disease (CKD) model without metabolic acidosis in which GFR decline is mediated by acid (H(+)) retention through endothelin (ET) and mineralocorticoid receptors. To gain insight as to whether this mechanism might mediate GFR decline in humans, we explored whether macroalbuminuric subjects with moderately reduced (CKD stage 2 = 60-90 ml/min; CKD 2) compared with normal estimated GFR (> 90 ml/min; CKD 1), each without metabolic acidosis, have H(+) retention that increases plasma levels of ET-1 and aldosterone. Baseline plasma ET and aldosterone concentrations were each higher in CKD 2 than CKD 1. Baseline dietary H(+) and urine net acid excretion (NAE) were not different between groups, but an acute oral NaHCO3 bolus reduced urine NAE less (i.e., postbolus urine NAE was higher) in CKD 2 than CKD 1, consistent with greater H(+) retention in CKD 2 subjects. Thirty days of oral NaHCO3 reduced H(+) retention in CKD 2 but not CKD 1 subjects and reduced plasma ET and aldosterone in both groups but to levels that remained higher in CKD 2 for each. Subjects with CKD stage 2 eGFR and no metabolic acidosis nevertheless have H(+) retention that increases plasma ET and aldosterone levels, factors that might mediate subsequent GFR decline and other untoward vascular effects.

Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.

Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR.

Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment of metabolic acidosis in patients with low glomerular filtration rate reduced the progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting enzyme inhibition. Thirty patients were then prescribed sodium citrate, and the remaining 29, unable or unwilling to take sodium citrate, served as controls. All were followed for 24 months with maintenance of their blood pressure reduction. Urine endothelin-1 excretion, a surrogate of kidney endothelin production, and N-acetyl-beta-D-glucosaminidase, a marker of kidney tubulointerstitial injury, were each significantly lower, while the rate of estimated glomerular filtration rate decline was significantly slower. The estimated glomerular filtration rate was statistically higher after 24 months of sodium citrate treatment compared to the control group. Hence it appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition.

Seasonal abundance and spatio-temporal distribution of dominant xylem fluid-feeding hemiptera in vineyards of central Texas and surrounding habitats.

A survey of xylem fluid-feeding insects (Hemiptera) exhibiting potential for transmission of Xylella fastidiosa, the bacterium causing Pierce's disease of grapevine, was conducted from 2004 to 2006 in the Hill Country grape growing region of central Texas. Nineteen insect species were collected from yellow sticky traps. Among these, two leafhoppers and one spittlebug comprised 94.57% of the xylem specialists caught in this region. Homalodisca vitripennis (Germar), Graphocephala versuta (Say), and Clastoptera xanthocephala Germar trap catches varied significantly over time, with greatest counts usually recorded between May or June and August and among localities. A comparison of insect counts from traps placed inside and outside vineyards indicated that G. versuta is always more likely captured on the vegetation adjacent to the vineyard. C. xanthocephala was caught inside the vineyard during the summer. Between October and December, the natural habitat offers more suitable host plants, and insects were absent from the vineyards after the first freezes. H. vitripennis was caught in higher numbers inside the vineyards throughout the grape vegetative season. However, insects were also caught in the habitat near the affected crop throughout the year, and residual populations overwintering near vineyards were also recorded. This study shed new light on the fauna of xylem fluid-feeding insects of Texas. These results also provide critical information to vineyard managers for timely applications of insecticides before insect feeding and vectoring to susceptible grapevines.

Statins and dietary and serum cholesterol are associated with increased lean mass following resistance training.

BACKGROUND: Age-related muscle loss (sarcopenia) is a prevalent condition associated with disability and mortality. Exercise and optimal nutrition are interventions to prevent and treat sarcopenia, yet little is known, outside of protein, of the effect of common nutrition recommendations and medication use on exercise-related muscle gain. METHODS: Forty-nine community-dwelling, 60- to 69-year-old men and women completed 2 weeks of nutrition education (American Dietetic Association recommendations) followed by 12 weeks of high intensity resistance exercise training (RET) with postexercise protein supplementation and 3x/wk dietary logs. RESULTS: We observed a dose-response relationship between dietary cholesterol (from food logs) and gains in lean mass that was not affected by variability in protein intake. Serum cholesterol and the serum cholesterol lowering agent statin were also independently associated with greater increases in lean mass. Dietary cholesterol was not associated with serum cholesterol or the significant reduction in blood pressure observed, but trends were observed for altered plasma C-reactive protein. CONCLUSION: These data suggest that dietary and serum cholesterol contribute to the skeletal muscles' response to RET in this generally healthy older population and that some statins may improve this response.

Testing for spatial correlation in nonstationary binary data, with application to aberrant crypt foci in colon carcinogenesis.

In an experiment to understand colon carcinogenesis, all animals were exposed to a carcinogen, with half the animals also being exposed to radiation. Spatially, we measured the existence of what are referred to as aberrant crypt foci (ACF), namely, morphologically changed colonic crypts that are known to be precursors of colon cancer development. The biological question of interest is whether the locations of these ACFs are spatially correlated: if so, this indicates that damage to the colon due to carcinogens and radiation is localized. Statistically, the data take the form of binary outcomes (corresponding to the existence of an ACF) on a regular grid. We develop score-type methods based upon the Matern and conditionally autoregressive (CAR) correlation models to test for the spatial correlation in such data, while allowing for nonstationarity. Because of a technical peculiarity of the score-type test, we also develop robust versions of the method. The methods are compared to a generalization of Moran's test for continuous outcomes, and are shown via simulation to have the potential for increased power. When applied to our data, the methods indicate the existence of spatial correlation, and hence indicate localization of damage.