Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae.

Developing a novel technique for the efficient, noninvasive clinical evaluation of bone microarchitecture remains both crucial and challenging. The trabecular bone score (TBS) is a new gray-level texture measurement that is applicable to dual-energy X-ray absorptiometry (DXA) images. Significant correlations between TBS and standard 3-dimensional (3D) parameters of bone microarchitecture have been obtained using a numerical simulation approach. The main objective of this study was to empirically evaluate such correlations in anteroposterior spine DXA images. Thirty dried human cadaver vertebrae were evaluated. Micro-computed tomography acquisitions of the bone pieces were obtained at an isotropic resolution of 93µm. Standard parameters of bone microarchitecture were evaluated in a defined region within the vertebral body, excluding cortical bone. The bone pieces were measured on a Prodigy DXA system (GE Medical-Lunar, Madison, WI), using a custom-made positioning device and experimental setup. Significant correlations were detected between TBS and 3D parameters of bone microarchitecture, mostly independent of any correlation between TBS and bone mineral density (BMD). The greatest correlation was between TBS and connectivity density, with TBS explaining roughly 67.2% of the variance. Based on multivariate linear regression modeling, we have established a model to allow for the interpretation of the relationship between TBS and 3D bone microarchitecture parameters. This model indicates that TBS adds greater value and power of differentiation between samples with similar BMDs but different bone microarchitectures. It has been shown that it is possible to estimate bone microarchitecture status derived from DXA imaging using TBS.

Tissue quantification of radioiodine thyroid uptake in humans by an isotopic imaging technique on slides.

BACKGROUND: Thyroid metabolism involves iodine, which allows us to use radioactive iodine for diagnostic and therapy purposes. The efficiency of radioiodine therapy depends on several parameters; the ability of thyroid tissue to uptake radioactive iodine is one of them. OBJECTIVE: The objective of this work is to quantify the radioactive iodine uptake on thyroid tissue. METHODS: In this work, we developed a method to quantify the in vivo uptake of iodine-131 on sections of thyroid glands removed by thyroidectomies. We performed an analysis of histological sections of the thyroid tissue by beta imaging. We had the opportunity to quantify the fixed radioactivity and to analyze its distribution in the thyroid gland, thanks to the good spatial resolution available with the type of detector used. RESULTS: The results gave a high image resolution showing the heterogeneity of iodine-131 fixation by the thyroid tissue. We were able to quantify the tissue radioactivity in mega Becquerel (MBq) per volume unit. CONCLUSION: This work has shown that the direct quantification of the thyroid tissue uptake is possible using the beta imaging system.

In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease.

BACKGROUND: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28. RESULTS: All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants. CONCLUSION: Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. TRIAL REGISTRATION: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease.

BACKGROUND: Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)? METHODS: Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m2 or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux. RESULTS: The patients were mainly men (44/75), aged 62 +/- 13 yrs, with long-standing diabetes (duration:17 +/- 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m2, AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 +/- 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) micromol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) micromol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5). CONCLUSIONS: Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.

Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study.

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age- and spine BMD-matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.

Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments.

Comparison of the radiolabeled PSMA-inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2 in primary prostate cancer samples.

PURPOSE: Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer. PROCEDURES: We retrospectively studied 20 frozen prostatectomy samples with various metastatic risks of the D'Amico classification. Tissue samples were investigated by tissular microimaging using the radiolabeled PSMA inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2. Bindings of the two radiopharmaceuticals were compared to histology and clinico-biological data (Gleason score, PSA values, metastatic risks). RESULTS: Binding of 111In-PSMA-617 was high whatever the metastatic risk (p = 0.665), Gleason score (p = 0.555), or PSA value (p = 0.404) while 111In-RM2 exhibited a significantly higher binding in the low metastatic risk group (p = 0.046), in the low PSA value group (p = 0.001), and in samples with Gleason 6 score (p = 0.006). CONCLUSION: PSMA and GRP-R based imaging might have complementary performances for the initial characterization of prostatic tumors. Prospective clinical studies comparing the two tracers in this setting are needed.

Nutritional status in patients with diabetes and chronic kidney disease: a prospective study.

BACKGROUND: A poor nutritional status reduces the life expectancy of diabetes patients undergoing hemodialysis. OBJECTIVE: The study objective was to specify the nutritional outcome in patients with chronic kidney disease (CKD) and well-controlled diabetes. DESIGN: Forty-five diabetes patients with CKD were enrolled in a cooperative-care program designed to control glucose, blood pressure, LDL cholesterol, and the albumin excretion rate (AER). Their glomerular filtration rate (GFR), body composition, serum albumin (SA), and resting energy expenditure were assessed and compared at baseline and 2 y later. RESULTS: Thirty-five patients did not start dialysis. Their glycated hemoglobin, blood pressure, LDL cholesterol, and AER improved; their GFR declined slowly (-3.3 mL x min(-1) x 1.73 m(-2) x y(-1)). Their body mass index (BMI), lean body mass, and SA increased. The GFR decline was correlated negatively with the initial BMI (r = -0.37, P < 0.05) and positively with the initial GFR (r = 0.34, P < 0.05). Ten patients started hemodialysis: except for higher total body water (P < 0.05) and extracellular volume (P < 0.01), their initial nutritional status did not differ significantly from that of 10 patients with comparable baseline severe CKD but without dialysis. At the second evaluation, patients on hemodialysis lost lean body mass, and their SA was lower than that of the patients with severe CKD (P = 0.05); lean body mass was unchanged and SA was higher (P = 0.01) in the patients with severe CKD. No significant difference was detected for resting energy expenditure. CONCLUSIONS: Nutritional status improved in CKD patients with well-controlled diabetes without dialysis, and it deteriorated in patients who started dialysis. A high initial BMI was associated with a slower decline in GFR.

Truncal distribution of fat mass, metabolic profile and hypothalamic-pituitary adrenal axis activity in prepubertal obese children.

OBJECTIVE: To investigate whether truncal distribution of fat mass (TDFM) is associated with variations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in prepubertal obese children. STUDY DESIGN: TDFM, assessed with dual energy X-ray absorptiometry and a comprehensive set of measures of HPA axis activity and reactivity have been studied in 45 prepubertal obese children aged 6 to 11 years (girls) and 6 to 13 years (boys). RESULTS: After adjustment for whole body fat mass (%) (WBFM), TDFM correlated positively with insulin (r = 0.50, 95% CI [0.23; 0.70]) and homeostasis model assessment of insulin resistance (r = 0.52, 95% CI [0.25; 0.71]). When adjusted for WBFM, TDFM correlated positively with morning plasma cortisol (r = 0.38, 95% CI [0.15; 0.64]) in the total population. TDFM correlated negatively with the rise of salivary cortisol after a standard meal (r = -0.43, 95% CI [-0.71; -0.02]), obviously in girls. When adjusted for WBFM and TDFM, morning plasma cortisol correlated positively with total cholesterol (r = 0.41, 95% CI [0.11; 0.65]) and triglyceride (r = 0.44, 95% CI [0.14; 0.67]). The rise of salivary cortisol after a standard meal was negatively (r = -0.56, 95% CI [-0.85; -0.01]) and positively (r = 0.74, 95% CI [0.16; 0.94]) correlated with homeostasis model assessment of insulin resistance in boys and girls, respectively. CONCLUSIONS: Association exists in prepubertal obese children between TDFM and markers of HPA axis activity. These data suggest that HPA axis could be involved early in life in obesity associated with pejorative metabolic profile.

Glucose control influences glomerular filtration rate and its prediction in diabetic subjects.

OBJECTIVE: Hyperglycemia increases glomerular filtration rate (GFR), but the influence of HbA(1c) (A1C) on GFR and GFR's prediction by recommended equations remains to be determined. RESEARCH DESIGN AND METHODS: In 193 diabetic patients, we searched for an association between A1C and isotopically measured GFR (51Cr-EDTA) and their predictions by the Cockcroft and Gault formula (CG) and the modification of diet in renal disease (MDRD) equation. Their accuracy for the diagnosis of moderate (GFR <60 ml/min per 1.73 m(2)) or severe (GFR <30 ml/min per 1.73 m(2)) renal failure was compared from receiver operating characteristic (ROC) curves, before and after categorizing the patients as well (A1C 8%. The MDRD equation was more accurate and robust in diabetic patients with impaired renal function.

Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is often encountered in diabetes, leading to several clinical complications. Our recent results showing an elevated tetrahydrocortisol/tetrahydrocorticosterone ratio in morning urine of diabetic children compared to that of controls suggest an increased nocturnal activity of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) in the former. QUESTION: We hypothesized that these observations could be explained by a reduced inhibition of hepatic 11ß-HSD1 activity by exogenous insulin owing to its subcutaneous (SC) administration and absence of first hepatic passage. Additionally, we hypothesized that hippocampal 11ß-HSD1 activity might also be impaired by diabetes. METHODS: We therefore measured HPA axis activity and 11ß-HSD1 expression and activity in liver and hippocampus in streptozotocin-induced diabetic juvenile rats treated with SC or intraperitoneal (IP) insulin. RESULTS: Plasma corticosterone levels were elevated in untreated diabetic rats during the resting phase and restored by both types of insulin treatment. The mRNA expression and activity of 11ß-HSD1 were increased in the untreated diabetic group in liver. Although diabetes was controlled equally whatever the route of insulin administration, liver 11ß-HSD1 gene expression and activity was decreased only in the IP group, suggesting that a first hepatic pass is needed for 11ß-HSD1 hepatic inhibition. In hippocampus, 11ß-HSD1 activity was elevated in the untreated diabetic group but restored by both types of insulin treatment. Thus, these data extend our findings in diabetic children by showing impairment of hippocampal 11ß-HSD1 in diabetes and by demonstrating that IP is preferable to SC insulin administration to restore 11ß-HSD1 activity in liver.

Cockcroft-Gault formula is biased by body weight in diabetic patients with renal impairment.

The Cockcroft-Gault (CG) formula and the modification of diet in renal disease (MDRD) equation are commonly used to estimate glomerular filtration rate (GFR), but their validity at extreme body weight is questionable. This may be significant for diabetic patients. In 122 diabetic patients with renal damage, we compared both estimates to isotopically determined GFR by correlation studies and a Bland and Altman procedure before and after categorizing the patients according to body mass index (BMI). Over the whole population, the CG overestimated GFR (CG, 51.4 +/- 23.1 mL/[min . 1.73 m2]; isotopic GFR, 44.6 +/- 21.1 mL/[min . 1.73 m2], P < .0001). The MDRD (45.2 +/- 17.9; NS vs isotopic GFR) did not overestimate GFR, but it underestimated high GFR as revealed by the Bland and Altman procedure (r = -0.26, P < .005). The CG underestimated GFR in patients with normal BMI (-14%, P < .01) and overestimated it in overweight (15%, P < .005) and obese patients (55%, P < .0001); the result and the error of the estimation were correlated with BMI. This bias did not affect the MDRD. The use of ideal instead of measured body weight improved the CG prediction, but underestimated GFR. As the BMI of the 87 type 2 diabetic subjects was higher, the CG overestimated their mean GFR by 18% (P < .001), whereas the MDRD did not. There were 25% fewer patients with delayed referral using the MDRD than with the CG. Because the estimate of GFR by the CG is proportional to body weight, it is not suited for obese diabetic patients. Although it is less easy to calculate, the MDRD is not affected by weight, and its use would avoid delay in referral to nephrologists.

Long-term evolution of body composition after renal transplantation: 5-year survey.

BACKGROUND: Thanks to advancements in immunosuppression, patients are living longer with kidney transplants, and nonimmunologic factors (particularly nutritional) have become a major source of morbidity and mortality after successful kidney transplantation (KTx). In this current study, we have prospectively assessed, in a cohort of kidney transplant recipients (KTR), the course of some nonimmunologic factors liable to hinder the long-term outcome of KTR. METHODS: Forty-four consecutive KTR with stable functioning grafts received dietary recommendations and were on the lowest effective dose of steroids. Biochemical nutritional markers, C-reactive protein, lipid profile, and body composition determined by dual-energy X-ray absorptiometry were studied over the first year, 2 years, and 5 years after KTx. RESULTS: No patients died during the follow-up. All patients but 2 were considered normotensive. Clinical diabetes developed in 3 patients. Visceral proteins stabilized at a normal range after the first year. Most of the patients normalized their inflammatory status. A significant improvement in lipid profile was observed. Female patients had a significant increase of weight (13.5%), mainly because of an increase in fat mass: 3.4 kg (19.4%) at 1 year and 5.6 kg (29.7%) at 2 years. In male patients, body composition remained stable and close to baseline values. The evolution of bone mass varied according to gender, total corticoid doses, and calcineurin inhibitors. Patients on low doses of steroids normalized their Z-score over the 5-year period. The increase in bone mass (paired t-test, P = .006) was only significant in patients treated with tacrolimus (analysis of variance for repeated measures, P < .001). CONCLUSIONS: Simple measures and dietary intervention to prevent or correct nonimmunologic disorders should permit improvement of long-term morbidity and mortality of KTR without compromising the functional outcome of their transplant.

Estimation of glomerular filtration rate in diabetic subjects: Cockcroft formula or modification of Diet in Renal Disease study equation?

OBJECTIVE: The Cockcroft-Gault formula is recommended for the evaluation of renal function in diabetic patients. The more recent Modification of Diet in Renal Disease (MDRD) study equation seems more accurate, but it has not been validated in diabetic patients. This study compares the two methods. RESEARCH DESIGN AND METHODS: In 160 diabetic patients, we compared the Cockcroft-Gault formula and MDRD equation estimations to glomerular filtration rates (GFRs) measured by an isotopic method ((51)Cr-EDTA) by correlation studies and a Bland-Altman procedure. Their accuracy for the diagnosis of moderately (GFR <60 ml . min(-1) . 1.73 m(-2)) or severely (GFR <30 ml . min(-1) . 1.73 m(-2)) impaired renal function were compared with receiver operating characteristic (ROC) curves. RESULTS: Both the Cockcroft-Gault formula (r = 0.74; P < 0.0001) and MDRD equation (r = 0.81; P < 0.0001) were well correlated with isotopic GFR. The Bland-Altman procedure revealed a bias for the MDRD equation, which was not the case for the Cockcroft-Gault formula. Analysis of ROC curves showed that the MDRD equation had a better maximal accuracy for the diagnosis of moderate (areas under the curve [AUCs] 0.868 for the Cockcroft-Gault formula and 0.927 for the MDRD equation; P = 0.012) and severe renal failure (AUC 0.883 for the Cockcroft-Gault formula and 0.962 for the MDRD equation; P = 0.0001). In the 87 patients with renal insufficiency, the MDRD equation estimation was better correlated with isotopic GFR (Cockcroft-Gault formula r = 0.57; the MDRD equation r = 0.78; P < 0.01), and it was not biased as evaluated by the Bland-Altman procedure. CONCLUSIONS: Although both equations have imperfections, the MDRD equation is more accurate for the diagnosis and stratification of renal failure in diabetic patients.

Early evolution of nutritional status and body composition after kidney transplantation.

BACKGROUND: Previous series have dealt with nutritional status after kidney transplantation. However, few studies have described the outcome of body composition after kidney transplantation. METHODS: A total of 44 cadaver kidney transplant recipients (28 men and 16 women) were followed prospectively during the first post-transplant year. Biochemical nutritional markers, dietary records, anthropometric measurements, and body composition were assessed at kidney transplantation and 3, 6, and 12 months later. RESULTS: By the end of the first year, serum albumin level was not significantly different from initial values. Prealbumin and retinol binding protein decreased from 42.3 +/- 10.2 mg/dL to 30.4 +/- 6.3 mg/dL and from 1.96 +/- 0.61 g/dL to 0.65 +/- 0.2 g/dL (P < 0.0001). Separating patients by gender showed that dietary caloric and protein intake increased in women only. At the end of the follow-up period, mean weight change was +5.4 kg in women (P = 0.009) and -0.9 kg in men (not significant). Body composition analyses showed that in women total fat and lean masses increased (+2.1 kg, P = 0.05, and +2.4 kg, P = 0.006), whereas in men total fat mass decreased (-1.4 kg, P = 0.04), and total lean mass tended to increase (+0.5 kg, not significant). Percentage change in total bone mass was +1.4% in women (not significant) and -2.1% in men (P = 0.05). In multivariate analyses, an independent impact of female gender on weight gain was observed, although increased fat mass was related only to energy intake. Increased total lean mass was related to low steroid doses and the absence of acute rejection and delayed graft function. Bone loss was related to male gender and high steroid doses. CONCLUSION: Changes in body composition during the first year after kidney transplantation are modulated by gender, energy intake, steroid doses, the occurrence of acute rejection, and delayed graft function.

Partial bilateral mesencephalic lesions affect D1 but not D2 binding in both the striatum and cortex.

The substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) are the two major mesencephalic dopaminergic systems. Mesencephalic dopamine denervation is followed by long-term modifications in striatum and cortex that preserve dopamine functions. Here, we have studied the impact of isolated bilateral 6-hydroxydopamine lesioning of the SNc or the VTA on D(1) and D(2) dopamine receptor binding in striatal and cortical areas of rat. Neither SNc nor VTA bilateral partial lesioning changed D(2) binding at the striatal or cortical level. Intriguingly, only VTA lesioning increased D(1) binding in the cortex, whereas both bilateral partial lesioning of the SNc or the VTA increased striatal D(1) binding. This suggests that increased cortical D(1) binding could be an indicator of VTA lesioning. Further behavioural experiments may explain the pathophysiological meaning of increased cortical D(1) binding, and determine whether this observation is involved in compensatory mechanisms.

Serum leptin, body fat, and nutritional markers during the six months post-kidney transplantation.

Leptin is a 16-kd protein that is thought to be a regulator of food intake and body weight. Many previous studies have reported elevated serum leptin levels in renal failure. In this study, we investigated the outcome of serum leptin and its relationship to body fat (BF), dietary intake, nutritional, and inflammatory markers after kidney transplantation (KTx). A total of 41 kidney transplant recipients were followed-up prospectively during 6 months posttransplantation. Serum leptin, albumin, transferrin, and C-reactive protein (CRP) were measured at KTx, 15 days, 3, and 6 months later. Dietary intake and BF were determined at KTx, 3, and 6 months later. A decrease in serum leptin was observed early at day 15 after KTx; this decrease was significant only in patients with BF >/= 30% of body weight. The decrease was maintained at 3 and 6 months after KTx. In multivariate analysis, an independent impact of higher percentage BF at KTx on the decrease of serum leptin was observed. Serum leptin correlated positively with BF. Conversely, no correlation was found between changes of serum leptin and changes of dietary intake. Leptin correlated positively with CRP at KTx, but not after normalization of renal function. Changes of serum leptin levels were not correlated with those of serum albumin levels. In summary, hyperleptinemia at KTx is manifest in patients with a high percentage of BF. An early and maintained correction follows KTx. Serum leptin levels did not appear to affect alimentary intake at and after KTx.

Distribution of [14C]-trans-resveratrol, a cancer chemopreventive polyphenol, in mouse tissues after oral administration.

Trans-resveratrol, a phenolic compound present in wine, has been reported to be a potential cancer chemopreventive agent. However, although it has numerous biological activities in vitro, there are few data about its bioavailability and tissue distribution in vivo. The objectives of this study were to investigate the absorption and tissue distribution of 14C-trans-resveratrol following oral administration to mice. Male Balb/c mice were given a single oral dose of 14C-trans-resveratrol and were sacrificed at 1.5, 3 or 6 h postdose. The distribution of radioactivity in tissues was evaluated using whole-body autoradiography, quantitative organ-level determination and microautoradiography. In addition, identification of radioactive compounds in kidney and liver was done with high-performance liquid chromatography. Autoradiographic survey of mice sections as well as radioactivity quantification in various organs revealed a preferential fixation of 14C-trans-resveratrol in the organs and biological liquids of absorption and elimination (stomach, liver, kidney, intestine, bile, urine). Moreover, we show that 14C-trans-resveratrol derived radioactivity is able to penetrate the tissues of liver and kidney, a finding supported by microautoradiography. The presence of intact 14C-trans-resveratrol together with glucurono- and/or sulfoconjugates in these tissues was also shown. This study demonstrates that trans-resveratrol is bioavailable following oral administration and remains mostly in intact form. The results also suggest a wide range of target organs for cancer chemoprevention by wine polyphenols in humans.

Body composition of patients on a very low-protein diet: a two-year survey with DEXA.

BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.