Reproducibility of a novel computed-tomography based measurement of renal papillary density in the Framingham Heart Study.

BACKGROUND: Renal papillary calcification is a compelling candidate risk factor for chronic kidney disease (CKD) and nephrolithiasis. Renal papillary density (RPD), as assessed by computed tomography (CT), is a potential marker for calcification that has not been well studied. We developed a protocol to measure RPD using CT scans and assessed its reproducibility in participants from the Framingham Heart Study. METHODS: We assessed RPD of right kidneys from a single abdominal CT slice in 100 representative participants from the Framingham Heart Study (47% female, mean age 59.9 years) using a novel protocol. We selected the kidney slice with the most open sinus space and assessed RPD using the average of three 20 mm(2) ellipses from upper, middle and lower papillary regions. Two different readers performed RPD measurements and the first reader repeated all measurements to determine both intra- and inter-reader reproducibility, respectively. RESULTS: Of 100 total individuals included in the replication dataset, six were excluded for poor scan quality. Average RPD across all individuals was 48.7 ± 4.7 (range 38.7-61.7) Hounsfield Units (HU). The intra- and inter-reader correlation coefficients were 0.86 and 0.79, respectively. Bland-Altman analysis suggested no systematic bias between the different reads. CONCLUSION: Measuring RPD is practical and reproducible using MDCT scans from a small sample of a community-based cohort.

The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally.

BACKGROUND: Alterations in the cellular characteristics of subcutaneous adipose tissue (SAT) may reduce its ability to expand in times of caloric excess, increasing the propensity to store excess calories viscerally (visceral adipose tissue [VAT]). We hypothesized (1) that increased SAT density, an indirect marker of fat quality, would be associated with an increased VAT/SAT ratio and increased cardiovascular disease (CVD) risk and (2) that these associations would be independent of the absolute volume of SAT. METHODS: We investigated the association of SAT density with the VAT/SAT ratio and CVD risk in 3212 participants (48% women, mean age, 50.7 years) from the Framingham Heart Study. Adipose tissue depot density and volume were quantified by computed tomography; traditional CVD risk factors were quantified. RESULTS: Higher SAT density was correlated with a higher VAT/SAT ratio in men (r = 0.17; P < .0001) but not in women (r = 0.04; P ≥ .05). More adverse levels of CVD risk factors were observed in the high SAT density/high VAT/SAT ratio group than in the referent group (low density/low ratio). For example, women had an increased risk of diabetes (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.6-17.6; P = .0001) and hypertension (OR, 1.6; 95% CI, 1.1-2.4; P = .009). Additional adjustment for SAT volume generally strengthened these associations (diabetes OR, 10.8; 95% CI, 4.1-29.0; hypertension OR, 2.5; 95% CI, 1.7-3.7; all P < .0001). These trends were similar but generally weaker in men. CONCLUSION: High fat density, an indirect marker of fat quality, is associated with the propensity to store fat viscerally vs subcutaneously and is jointly characterized by an increased burden of CVD risk factors.

Effect of body size on expression of Manduca sexta midgut genes.

Isometric growth of larval insect midgut predicts that the ratio of midgut surface area to body mass decreases as larvae grow. Gut tissue and gut content masses were measured in first through fifth instar Manduca sexta larvae. Wet mass of gut tissue increased in relationship to body mass with a scaling exponent of 0.85 compared to an exponent of 1.33 for gut content mass, suggesting that surface area becomes increasingly limiting in larger larvae. To test the hypothesis that compensation for the decrease in relative surface area of the midgut occurs by increased expression of membrane proteins, we compared midgut mRNA expression in fourth and fifth instar. Surveyed genes encoded apical membrane proteins with diverse functions, including the potassium amino acid transporter KAAT1, ion channel CAATCH1, aminopeptidase msAPN3, V-type H-ATPase E subunit, and cation chloride cotransporter masBSC. KAAT1 was expressed 300- to 1500-fold higher in middle and posterior midgut compared to anterior midgut. Expression of msAPN3 was approximately 200-fold higher in posterior midgut than middle midgut. Expression of KAAT1 was 2.3- to 3.1-fold higher in fifth compared to fourth-instar larvae, and masBSC expression was 1.3- to 1.9-fold higher in fifth-instar larvae. Expression of msAPN3 and V-ATPase, but not KAAT1, decreased as body mass increased within the fifth instar. Although the increased expression of KAAT1 and masBSC in fifth-instar larvae supports the hypothesis of increased membrane protein expression in larger larvae, results from the other genes do not support this hypothesis.