p-Cresol and Cardiovascular Risk in Kidney Transplant Recipients.

p-Cresol Sulphate (pCS) is a uremic toxin that originates exclusively from dietary sources and has a high plasma level related to chronic kidney disease (CKD) and cardiovascular disease (CVD). The aim of our study was to evaluate the plasma levels of pCS in kidney transplant recipients (KTRs) related to estimated glomerular filtration rate (eGFR), traditional risk factors, cardiovascular clinical events and endothelial progenitor cells (EPCs), bone marrow-derived cells for the vascular repair system. We considered 51 KTRs and 25 healthy blood donors (HBDs). pCs levels were analyzed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry with an electrospray ionization (ESI) (LC/ESI-MS/MS) on a triple-quadrupole; EPCs were analyzed using flow cytometric analysis. eGFR was 52.61 ± 19.9 mL/min/1.73 m(2) in KTRs versus 94 ± 21 mL/min/1.73 m(2) in HBDs. We did not find differences in pCS levels between KTRs and HBDs. Levels of pCS were inversely related with eGFR in KTRs and pCS levels were significantly lower in KTRs with eGFR <30 mL/min/1.73 m(2) versus eGFR >30 mL/min/1.73 m(2). Furthermore, there was a difference in pCS levels between eGFR <30 mL/min/1.73 m(2) of KTRs compared with HBDs. Levels of pCS were almost significantly influenced by the presence of a previous vascular event and were inversely related with mature EPCs. These findings suggest that KTRs should not have higher CVD risk than HBDs and their physiological vascular repair system appears to be intact. In KTRs the reduction of eGFR also increased pCS levels and reduced EPCs numbers and angiogenesis capacity. In summary, pCS acts as an emerging marker of a uremic state, helping assess the global vascular competence in KTRs.

Long-Term Prognostic Impact of Contrast-Enhanced Ultrasound and Power Doppler in Renal Transplantation.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) and power Doppler ultrasound (US) are established tools in the study of acute renal allograft (RA) dysfunction. The aim of this study was to investigate their long-term prognostic impact. MATERIALS AND METHODS: A total of 39 kidney recipients underwent CEUS and US at 5 and 15 days and at 1, 3, 6, and 12 months after grafting, with yearly clinical, laboratory, and US follow-up for a total of 4 years. CEUS analysis according to the gamma variate model was performed on cortical and medullary regions. Patients were divided into 2 subsets: death or graft failure vs patients with functioning grafts; higher vs lower than 50% glomerular filtration rate (GFR) reduction from the first month to the fourth year after grafting. Receiver-operator characteristic (ROC) analysis for death/graft failure and 50% GFR reduction events was performed for variables with significant differences between groups (t test) or with significant correlation to GFR (Pearson correlation). RESULTS: ROC analysis confirms the reliability of clinical and radiologic variables for the evaluation of long-term graft survival or of GFR reduction, with high sensitivity (for resistive index) or specificity (for GFR, medullary peak, and regional blood flow). CONCLUSIONS: Combining CEUS and US allows the evaluation of long-term RA function in terms of GFR reduction and graft survival. Resisitive-indexes show a good sensitivity, relating to kidney disfunction, while CEUS parameters show a good specificity, identifiying well-perfused grafts.

Everolimus, cyclosporine, and thrombotic microangiopathy: clinical role and preventive tools in renal transplantation.

INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by endothelial cell injury and formation of fibrin thrombi within capillary and arterioles. In renal allograft recipients, TMA mainly presents as hemolytic uremic syndrome. Its occurrence is rare, and diagnosis requires a high degree of suspicion. Drug toxicity, in particular from calcineurin inhibitors (CNIs) and mTOR inhibitors (mTORi), is the most common cause posttransplant and has recently been emphasized in the setting of lung transplantation. OBJECTIVE: The goal of this study was to investigate the role of mTORi as an added risk factor in the development of TMA to propose strategies for modulation of immunosuppressive (IS) therapy. PATIENTS AND METHODS: From a database of 496 renal graft recipients, we analyzed 350 renal graft biopsy specimens gathered at our center from 1998 to 2012. In patients undergoing combined therapy with mTORi and CNI, we compared drugs levels in TMA-affected and TMA-free groups, using mTORi and CNI TLC and the summation of [everolimus TLC+(cyclosporine C2/100)] (Σ) as a surrogate marker of combined exposition to 2 drugs. Receiver-operating characteristic analysis of association of EVL TLC+(C2/100) was performed for patients exposed to mTORi. RESULTS: Histologic features of TMA were found in 36 patients (prevalence of 7.3%). The caseload was divided into 2 groups: not drug-related TMA (n=19) and drug-related TMA (n=17). Despite the prevalence of TMA in patients exposed to mTORi being greater (8 of 153; prevalence, 5.3%) compared with therapies without mTORi (9 of 324; prevalence, 2.8%), statistical difference was not reached. Patients treated with mTORi who developed de novo drug-related TMA had higher blood levels of IS drugs compared with those who did not develop TMA. Receiver-operating characteristic analysis found a significant threshold of 12.5 ng/mL (area under the curve, 0.803; P=.006). CONCLUSIONS: Results confirm the pivotal role of IS drugs in the onset of de novo TMA. On the basis of literature, we could speculate a sequence of endothelial damage by CNI, on which everolimus fits hindering the repair of endothelial injury. Therefore, high blood levels of CNI and mTORi seem to predispose patients to posttransplant TMA. Combined monitoring of these 2 drugs might be used to prevent the complication. Σ [everolimus TLC + (cyclosporine C2/100)]>12.5 ng/mL should be avoided as a surrogate risk factor for adverse effects.

Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting further detailed exercise protocols and to fostering improved posttransplantation health and survival, helping to ensure that physical activity becomes a safe routine medical treatment plan of patient management.

Contrast-enhanced sonography in early kidney graft dysfunction.

OBJECTIVES: The aim of this study was a comparison of contrast-enhanced sonography (CEUS) and power Doppler ultrasound (US) findings in renal grafts within 30 days posttransplantation. METHODS: A total of 39 kidney recipients underwent CEUS (SonoVue bolus injection) and US examinations at 5 (T0), 15 (T1), and 30 (T2) days after grafting. The results were correlated with clinical findings and functional evolution. Fourteen patients displayed early acute kidney dysfunction: 10 had acute tubular necrosis (acute tubular necrosis [ATN] group); four acute rejection episodes (ARE group); 25 with normal evolution (as control, C group). Renal biopsies were performed to obtain a diagnosis in the four ATN cases and in all ARE patients. Creatinine and estimated glomerular filtration rate were used as kidney function parameters. CEUS analysis was performed both on cortical and medullary regions while US resistivity indexes (RI) were obtained on main, infrarenal, and arcuate arteries. From an analysis of CEUS time-intensity curves, we computed peak enhancement (PEAK), time to peak (TTP), mean transit time (MTT), regional blood flow (RBF) and volume (RBV), and cortical to medullary ratio of these indies (RATIO). RESULTS: An increased RI was present in the ATN and ARE groups as well as a reduced PEAK and RBF. RATIO-RBV and RATIO-MTT were lower than C among ATN cases, while TTP was higher compared to C in ARE. No statistical difference was evidence for RI between ATN and ARE groups. MTT (T0) was significantly related to creatinine at follow-up (T2). CONCLUSIONS: US and CEUS identified grafts with early dysfunction, but only some CEUS-derived parameters distinguished ATN from ARE, adding prognostic information.

Fermented pigeon pea (Cajanus cajan) ingredients in pasta products.

Pigeon pea (Cajanus cajan var. aroíto) seeds were fermented in order to remove antinutritional factors and to obtain functional legume flour to be used as pasta ingredients. Fermentation brought about a drastic reduction of alpha-galactosides (82%), phytic acid (48%), and trypsin inhibitor activity (39%). Fermented legume flours presented a notable increase of fat and total soluble available carbohydrates, a slight decrease of protein, dietary fiber, calcium, vitamin B2, vitamin E, and total antioxidant capacity, and a decrease of soluble dietary fiber, Na, K, Mg, and Zn contents. No changes were observed in the level of starch and tannins as a consequence of fermentation. The fermented flour was used as an ingredient to make pasta products in a proportion of 5, 10, and 12%. The supplemented pasta products obtained had longer cooking times, higher cooking water absorptions, higher cooking loss, and higher protein loss in water than control pasta (100% semolina). From sensory evaluations, fortified pasta with 5 and 10% fermented pigeon pea flour had an acceptability score similar to control pasta. Pasta supplemented with 10% fermented pigeon pea flour presented higher levels of protein, fat, dietary fiber, mineral, vitamin E, and Trolox equivalent antioxidant capacity than 100% semolina pasta and similar vitamins B1 and B2 contents. Protein efficiency ratios and true protein digestibility improved (73 and 6%, respectively) after supplementation with 10% fermented pigeon pea flour; therefore, the nutritional value was enhanced.

[The use of deffated corn germ in flour manufactured to bakery products]. / Uso del gérmen desgrasado de maíz en harinas compuestas para panificación.

The flour of deffated corn germ is a by-product of the corn industry milling dried which is actually subutilized in human consumption. In this study, two samples of corn deffated germ of different particle size were physicochemically characterized: fine fraction (FF) and medium fraction (FM) and they were added to wheat flours to obtain composite flours with substitution levels of 5- 10- 12- 15% mixtures. These mixtures were used to manufacture sandwich bread in bakeries, which were physico-chemically and sensorially analyzed. (FF) and (FM) were found to provide from 20 to 35% of dietary fiber. From the manufactured bread loaves, the ones containing 10% of (FM) and 10% of (FF) were selected because they did not differ in specific weight, color, flavor and texture at a 95% confiability from those elaborated with 100% wheat flour. In the acceptability test given to 200 consumers, it was found that bread with 10% FF substitution was more widely accepted (48%) than that containing 100% wheat flour; and that of 10% of (FM) had the same level of acceptability (28%) as the control bread. It can be concluded that the deffated corn kernel represents a raw material available in this country that could be used in bread elaboration as a partial replacement for imported wheat.

[Substitution of ascorbic acid for potassium bromide in the making of French bread]. / Sustitución de bromato de potasio por ácido ascórbico en la elaboración de pan francés.

The potassium bromate (PB) is the flour improving additive for bread making, most widely used in Venezuela. This additive has been reported to have hazardous effects. For this reason it has been forbidden in various countries. In order to find a substitute for PB, the feasibility of using ascorbic acid (AA) in bread making flours was considered. Flours with 80, 40 and 20 ppm of AA were tested and contrasted with an experimental and industrial flour with 80 ppm of PB, maximum quantity allowed by the Venezuelan Legislation. The effect of these additives was evaluated on French bread, of high consumption in our country. It was found that the bread prepared using the flour containing 20 ppm of AA did not present significant differences from those made out of the pattern flour, concerning their organoleptic and physico-chemical properties. It was demonstrated that it is technically feasible to replaced 80 ppm of PB for 20 ppm of AA in the flours, without affecting the bread acceptability.