A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND). We studied 18 obese ND and 16 T2D undergoing three meal tolerance tests (MTT) on three occasions (breakfast, lunch, and dinner). We used plasma glucose, insulin, and FFA concentrations collected at breakfast to test a battery of models and selected the best one based on physiological plausibility, ability to fit the data, precision of parameter estimates, and the Akaike parsimony criterion. The best model assumes that the postprandial suppression of FFA lipolysis is proportional to the above basal insulin, while FFA disposal is proportional to FFA concentration. It was used to compare FFA kinetics in ND and T2D along the day. The maximum lipolysis suppression occurred significantly earlier in ND than T2D (39 ± 6 min vs. 102 ± 13 min, 36 ± 4 min vs. 78 ± 11 min, and 38 ± 6 min vs. 84 ± 13 min, P < 0.01, at breakfast, lunch, and dinner, respectively), making lipolysis significantly lower in ND than T2D. This is mainly attributable to the lower insulin concentration in the second group. This novel FFA model allows to assess lipolysis and insulin antilipolytic effect in postprandial conditions.NEW & NOTEWORTHY In this study, we propose a new mathematical model able to quantify postprandial FFA kinetics and adipose tissue insulin sensitivity in both subjects with obesity without type 2 diabetes (ND) and subjects with type 2 diabetes (T2D). Results show that the slower postprandial suppression of lipolysis in T2D contributes to the higher free fatty acid (FFA) concentration that, in turn, may contribute to hyperglycemia.

A field tool for the aerobic power evaluation of middle-aged female recreational runners.

This study used time to exhaustion (TTE) to predict V̇O2max in female recreational master runners. Forty-two middle-aged women (mean = 40.5 ± 5.9 years) who had trained for recreational running performed two Université de Montréal Track Tests in the facilities of the University of Barcelona (Spain). The first was performed on a treadmill (t), the second, on an athletics track (field: f). After measuring TTE and V̇O2max on the treadmill, a first-order equation was obtained to estimate fV̇O2max from fTTE. No significant difference was observed between the estimated fV̇O2max (46.5 ± 2.9 mL·kg-1·min-1) and the measured tV̇O2max (46.2 ± 5.3), with a mean value of the absolute differences of less than 8% of the tV̇O2max average. High agreement between the two V̇O2max values was also evident, as shown by the low bias of the differences and the Bland-Altman plot. The equation obtained is of interest to evaluate performance in middle-aged female recreational runners. It will allow coaches and runners to set running paces for training and could be used in training routines to determine improvements after a training program. Moreover, these tools could be used in the field to assess the physical fitness of middle-aged women, in efforts to preserve their health and physical function.

Mushroom productivity trends in relation to tree growth and climate across different European forest biomes.

Although it is logical to think that mycorrhizal mushroom production should be somehow related to the growth of the trees from which the fungi obtain carbohydrates, little is known about how mushroom yield patterns are related to tree performance. In this study, we delved into the understanding of the relationships between aboveground fungal productivity, tree radial growth patterns and climatic conditions across three latitudinally different bioclimatic regions encompassing Mediterranean, temperate and boreal forest ecosystems in Europe. For this purpose, we used a large assemblage of long-term data of weekly or biweekly mushroom yield monitoring in Spain, Switzerland and Finland. We analysed the relationships between annual mushroom yield (considering both biomass and number of sporocarps per unit area), tree ring features (tree ring, earlywood and latewood widths), and meteorological conditions (i.e. precipitation and temperature of summer and autumn) from different study sites and forest ecosystems, using both standard and partial correlations. Moreover, we fitted predictive models to estimate mushroom yield from mycorrhizal and saprotrophic fungal guilds based on climatic and dendrochronological variables. Significant synchronies between mushroom yield and climatic and dendrochronological variables were mostly found in drier Mediterranean sites, while few or no significant correlations were found in the boreal and temperate regions. We observed positive correlations between latewood growth and mycorrhizal mushroom biomass only in some Mediterranean sites, this relationship being mainly mediated by summer and autumn precipitation. Under more water-limited conditions, both the seasonal wood production and the mushroom yield are more sensitive to precipitation events, resulting in higher synchrony between both variables. This comparative study across diverse European forest biomes and types provides new insights into the relationship between mushroom productivity, tree growth and weather conditions.

Comparison between single portal endoscopic and 1-cm open carpal tunnel release.

Given the controversy about the best surgical technique for carpal tunnel release, this study tested the hypothesis that no significant differences would be observed between single-portal endoscopic release and a short, 1-cm incision open release in a large sample of patients. Consecutive patients were assigned to one of the two techniques. Preoperative and postoperative measurements included grip and pinch strength, a visual analog scale for pain and a satisfaction questionnaire. Eighty-seven patients completed the study: 35 with an endoscopic release and 52 with an open release. Both techniques were effective and safe: grip and pinch strength decreased 1 month after surgery in both techniques but improved significantly at 6 and 12 months (P < 0.05) while the complication rate was low. Subjective results were judged to be "excellent or good" by more than 90% of patients in both groups. No significant between-technique differences in outcomes were observed thus, surgical decisions may be based on criteria other than effectiveness. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

Efectos agudos del ejercicio físico sobre el estado de ánimo y la HRV / Acute effects of exercise on mood and HRV

El objetivo del estudio es analizar los efectos agudos del ejercicio físico sobre el estado de ánimo y la variabilidad de la frecuencia cardíaca (HRV), en personas activas y sedentarias. Para ello participaron 30 estudiantes clasificados en Activos y No activos. En una sola sesión realizaban una prueba de esfuerzo submáximo (UKK), cumplimentando el Perfil de Estados de Ánimo (POMS) y realizando un test en reposo de la HRV antes y después del ejercicio. Los resultados indican una mejora en el estado de ánimo, aumentando en los factores de Vigor y Fatiga y disminuyendo en Tensión y Depresión después del ejercicio. Se encontraron diferencias significativas en función del nivel de ejercicio físico de los participantes en el nivel de Depresión, al observarse una mayor disminución después del ejercicio en los Activos. La HRV también mostró diferencias entre Activos y No activos en los parámetros de dominio frecuencial, LFnu2 y HFnu2 (AU)

The aim of this study was to analyze the acute effects of exercise on mood and on heart rate variability (HRV), in active and sedentary people. This involved 30 undergraduates classified into Active and Non active participants. In a single session participants performed a submaximal exercise test (UKK), answered the Profile of Mood States (POMS) and performed before and after the exercise a test of HRV at rest. The participants improved their mood state, by increasing Vigor and Fatigue factors and decreased Tension and Depression after the exercise test. Moreover, Active participants presented a significant higher decrease in Depression after exercise than Non active. HRV analysis also showed differences between Active and Non active participants in the frequency domain parameters LFnu2 and HFnu2 (AU)

Impact of protease inhibitors on the evolution of urinary markers: Subanalyses from an observational cross-sectional study.

Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria [without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging problem in human immunodeficiency virus (HIV)-infected patients, although few data are available on the role of protease inhibitors (PIs) in this condition.To determine the time to kidney injury in a cohort of HIV-infected patients receiving a PI-containing regimen.We report the results of a subanalysis of a published cross-sectional study. The subanalysis included only patients receiving PI-containing regimens for more than 6 months (377 of the overall 970 patients). We determined associated factors and constructed receiver operating characteristic curves to estimate time to kidney injury depending on the PI used.The percentage of patients with kidney injury was 27.7% for darunavir, 27.9% for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229 days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity, 0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC, 0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339 days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity, 0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of lopinavir/ritonavir without tenofovir was a protective factor (odds ratio = 1.772; 95%CI, 1.070-2.93; P = 0.026).For all PIs, the percentage of patients with kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to kidney injury was recorded with lopinavir/ritonavir. These results demonstrate the need for renal monitoring, including urine samples, in patients receiving a PI-based regimen, even when tenofovir is not used concomitantly.

Outcomes of Monoclonal Gammopathy of Undetermined Significance in Patients Who Underwent Kidney Transplantation.

BACKGROUND: There are few reports about the clinical course and prognosis of monoclonal gammopathy of undetermined significance (MGUS) in long-term immunosuppressed patients. Our aim was to study the association and evolution of MGUS and renal transplantation. METHODS: Subjects submitted to renal transplantation between 1996 and 2011 who presented MGUS before or after immunosuppressive treatment was established were selected. RESULTS: Patients (N = 587) underwent kidney transplantation in our center during the selected period. MGUS was detected in 17 (2.9%) patients (10 men and 7 women with a mean age of 69.9 ± 10.07 years), with a median follow-up of 6 years. All patients had a functioning graft. Nine had MGUS before transplantation. One patient had multiple myeloma, and 8 remained stable. Eight patients had development of MGUS after transplantation. Six patients remained stable, 1 showed no MGUS, and 1 displayed an increased monoclonal component in further controls. CONCLUSIONS: In our study, renal transplantation is not a risk factor for the development of malignant processes in patients with MGUS before transplantation. There is a group of patients who tend to have MGUS after transplantation; nevertheless, they had a benign evolution during a 6-year follow-up.

Recurrent Glomerulonephritis in Renal Transplantation: Experience in Our Renal Transplantation Center.

BACKGROUND: Post-transplant recurrent glomerulonephritis (RGN) is the third cause of graft failure in the first year after renal transplantation (RT). The purpose of this study was to analyze the incidence of RGN, clinical presentation, and clinical evolution of transplanted renal graft in patients who underwent RT at our center. METHODS: We studied patients with glomerulonephritis (GN) who underwent RT (2007 to 2013).We analyzed sex, age, time in dialysis, type of GN, type of RT, time to post-transplant RGN, kidney function at the time of diagnosis of RGN, and renal graft evolution. Renal biopsy samples were processed in the anatomic pathology laboratory. RESULTS: Three hundred sixteen patients received kidney transplantation during this time period. In 83 cases, the reason for transplantation was primary GN. Of these 83 patients, 15 (18%) had RGN confirmed by renal biopsy. Data for these 15 patients include sex: 73.3% men, 26.7% women; mean age: 42.2 (29-73) years; type of RT: 80% cadaveric donor (CD) versus 20% living donor (LD); type of GN: 18.4% immunoglobulin (Ig)A nephropathy, 35.7% membranous GN, 10.53% type I membrano-proliferative GN (MPGN I), and 16.6% focal segmental glomerular sclerosis (FSGS). The mean time to post-transplant RGN was 2 years (1 month to 16 years). Patients who received an LD transplant had a shorter time to post-transplant RGN than those who had a CD transplant. One patient with FSGS and one with MPGN I had a time to post-transplant RGN of less than 1 year. In the evolution of renal function, 33.3% of patients had graft failure. CONCLUSIONS: The incidence of RGN was lower (18%) than that published in the literature. Membranous nephropathy was the most frequent cause of post-transplant RGN. Patients who underwent LD transplantation and those with IgA nephropathy had a shorter interval of time to post-transplant RGN than patients with FSGS and MPGN I.

Late Onset of Cholesterol Embolism Leading to Graft Failure After Renal Transplantation: Report of Two Cases.

Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.

Nodular Arteriolar Hyalinosis as Histopathologic Hallmark of Calcineurin Inhibitor Nephrotoxicity: Does It Always Have the Same Meaning?

INTRODUCTION: Nodular arteriolar hyalinosis (NAH) is a typical, although not specific, histological finding of calcineurin inhibitor toxicity (CNIT). The objective of our study was to assess the reason why some patients showing strong NAH in renal graft biopsies who underwent calcineurin inhibitor (CNI) withdrawal presented very poor outcome whereas others improved graft function. MATERIAL AND METHODS: We performed 207 renal graft biopsies between January 2011 and May 2014 due to clinical criteria. In 13 patients CNI withdrawal was performed, and the major histopathological finding was severe NAH. The results after this action were analyzed. RESULTS: We selected 2 groups: good outcome and poor outcome. Eight patients showed good results including stabilization or improvement of graft function. Five patients presented poor results requiring chronic hemodialysis. C4d staining was negative in all biopsy specimens, and peritubular capillaritis was not observed. To identify potential prognostic markers we retrospectively reviewed biopsy samples looking for minor or nonspecific features, especially inflammation scores both global and on fibrotic areas as per Banff classification. Mean serum creatinine level at time of biopsy and mean arteriolar hyalinosis score did not show significant differences between both groups. In contrast, the poor results group presented a higher mean global inflammation score compared with the good results patients. CONCLUSIONS: NAH is not a risk factor for poor renal graft outcome by itself. Other histopathologic findings, usually considered as secondary markers, like the inflammation score, should be considered before deciding CNI withdrawal.

Pattern of Tuber melanosporum extramatrical mycelium expansion over a 20-year chronosequence in Quercus ilex-truffle orchards.

Successful cultivation of black truffle (Tuber melanosporum) requires a long-term investment and the maintenance of the symbiosis throughout its preproductive and productive years. Monitoring the symbiosis over time is challenging, as it requires methods that can detect the belowground proliferation of the fungus associated with its host tree. In this study, we used a chronosequence design to study the expansion pattern of this fungus as the host tree grows. We hypothesize that this expansion can be estimated by monitoring T. melanosporum DNA from soil beneath host trees of different ages (3, 5, 7, 10, 14, and 20 years old) and at different distances from the trunk of the trees (40, 100, and 200 cm). We also wished to evaluate the presences of Tuber brumale and Tuber indicum, potentially problematic truffle species, in these plantations. To detect the mycelium of T. melanosporum in these soils, we extracted DNA and performed polymerase chain reaction (PCR) with Tuber species-specific primers, and to estimate DNA amount, we measured relative band intensities from the amplicons in agarose gels. Both age and distance were related to T. melanosporum DNA quantity, which was more abundant in the oldest age classes, reaching a plateau in 5-7 years. At 40 cm from the tree, there were no differences in T. melanosporum DNA amounts in orchards of different ages, but at 100 and 200 cm, younger orchards had less T. melanosporum DNA. We did not detect DNA from T. brumale or T. indicum in any of our samples.

Evaluación de los sistemas de medición de la fuerza muscular en el ámbito de la práctica musical. Aproximación a un prototipo apto para la práctica instrumental / Evaluation of the systems for measuring muscle strength applied to musical practice. Approach to a prototype suitable for instrumental practice

Objetivo: Evaluar los sistemas de medida de la fuerza, en tiempo real, que ejerce la mano sobre el instrumento al tocar (piano y guitarra) y conocer la fuerza ejercida por la mano del músico, en tiempo real, sobre el instrumento. Material y Método: Se analizaron sobre el instrumento, en un guitarrista y un pianista experimentados. En cada sistema analizado se valoró: el grado de interferencia con el gesto técnico musical; la posibilidad de intercambiarlo de un instrumento a otro; la resistencia al deterioro con el uso (especialmente al trabajar sobre cuerdas); la existencia de un sistema y software de captura y análisis de los datos que permitiera al usuario definir alarmas o niveles de alerta útiles para poder hacer un trabajo de reeducación de la tensión utilizada para tocar (biofeedback). Se estableció un protocolo de pruebas y se experimentó sobre ambos instrumentos. Con el método que dio mejor resultado se procedió al estudio de la fuerza ejercida por la mano del músico sobre el instrumento. Resultados: Las medidas recogidas mostraron en el caso de la guitarra un pico de fuerza máximo de 9,14N (0,93Kg) y en el piano se superaban habitualmente los 9,8N (1kg de fuerza). Conclusiones: Los sensores de presión miniaturizados recubiertos con una funda de látex ultrafino han resultado ser eficaces para el estudio de la fuerza isométrica y concéntrica desarrollada por la mano del músico (AU)

Objetive: determine, in real time, its usefulness in the study of the force exerted by the hand of the musician on the instrument (piano and guitar) and the force exerted by the hand of the musician on the instrument, in real time. Material and methods: systems better adapted to the requirements of musical practice were chosen and analyzed on the instrument, using as experimental subjects a guitarist and a pianist. For every system examined the following was considered: the degree of interference with the musical technical act; easiness to swap the system from one instrument to another; resistance to deterioration with use (especially working on strings) and existence of a system and software to capture and analyze data that allow the user to set alarms or alert levels that will help him to do reeducation of the tension used to play (biofeedback) were analysed. Results: The guitar measures showed a maximum peak force of 9.14 N (0.93Kg) and the piano usually exceeded 9.8 N (1kg force). The other analized systems (thermal imaging, Chronopic, EMG and accelerometer) let us study the force, however important limiting factors behaved they were discarded. Conclusions: Miniature pressure sensors coated with an ultrathin latex sheath have proved effective for the study of the isometric and concentric force developed by the hand of the musician (AU)

Tratamiento con rituximab en la granulomatosis de Wegener refractaria a la terapia convencional / Rituximab therapy for Wegener's granulomatosis refractory to conventional treatment

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Cinacalcet may reduce arterial stiffness in patients with chronic renal disease and secondary hyperparathyroidism - results of a small-scale, prospective, observational study.

AIMS: This study evaluated the impact of cinacalcet on arterial stiffness, determined by pulse wave velocity (PWV), in patients with chronic renal disease and secondary hyperparathyroidism (SHPT). PATIENTS AND METHODS: This prospective, observational study included, SHPT patients with chronic renal disease on dialysis undergoing cinacalcet treatment with a follow-up of 12 months. RESULTS: 21 patients, 62% males, with a mean age of 51.3 years (± 18.0) were included. Cinacalcet was given for at least a year with a mean daily dose of 35 mg (range 30-60 mg). Aortic PWV significantly decreased after 12 months of cinacalcet treatment (9.35 ± 1.83 m/sg vs. 8.66 ± 1.86 m/sg; p = 0.030). Additionally, there was a notable reduction trend in the left ventricular mass index (166.6 ± 39.4 g/m² vs. 156.1 ± 31.8 g/m²), although it did not achieve statistical significance (p = 0.063). Alkaline phosphatase and PTH were significantly decreased during the study. However, serum calcium, phosphorus and blood pressure remained stable. CONCLUSION: The results of this study support the possibility that cinacalcet reduces arterial stiffness of SHPT patients with chronic renal disease after 12 months of treatment. Prospective, randomized clinical trials are needed to confirm these preliminary findings.

The formation of wrinkles in single-layer graphene sheets under nanoindentation.

We investigate the formation of wrinkles and bulging in single-layer graphene sheets using an equivalent atomistic continuum nonlinear hyperelastic theory for nanoindentation and nanopressurization. We show that nonlinear geometrical effects play a key role in the development of wrinkles. Without abandoning the classical tension field membrane theory, we develop an enhanced model based upon the minimization of a relaxed energy functional in conjunction with nonlinear finite hyperelasticity. Formation of wrinkles are observed in rectangular graphene sheets due to the combination of induced membrane tension and edge effects under external pressure.

Effect of low doses of atorvastatin on the urinary peptide profile of kidney transplant patients.

Statins are prescribed to reduce posttransplant dyslipidemia, which is frequent among kidney graft recipients. Their efficacy to reduce cholesterol levels has been accompanied by pleiotropic effects. Proteomics is the study of the expressed complement of proteins in tissues or biological fluids. It includes the identification of changes in proteins that occur in various states, eg, after drug administration. Our study objectives were: (1) to analyze the effect of atorvastatin (10 mg/d) on lipid profile, renal function, proteinuria, and inflammation parameters, such as C-reactive protein (CRP), and (2) to use proteomics to ascertain whether this treatment modified the patients' urinary peptide profiles seeking to understand the molecular actions of the drug. Urinary peptide profiles, lipids, renal function parameters (creatinine clearance), proteinuria, and CRP were determined in 39 patients at baseline and at 12 weeks after atorvastatin treatment (10 mg/d). The peptide fraction of each sample acquired using magnetic beads was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results showed that treatment with atorvastatin produced a significant reduction in lipid profile, but did not modify renal function (creatinine clearance), proteinuria, or CRP. The proteomic study showed that statin treatment did not produce significant changes in the urinary peptidome, although there was a tendency for some peptides to increase or decrease after the treatment.

Subclinical inflammation in renal transplant recipients: impact of cyclosporine microemulsion versus tacrolimus.

BACKGROUND: Renal insufficiency and renal transplant (RT) provoke a microinflammatory state that leads to increased atherosclerosis. It is not fully known whether calcineurin inhibitors (CNIs) play a role in the inflammation observed in these patients or whether any differences exist between CNIs. OBJECTIVES: The study aimed to establish differences in the inflammatory state of two groups treated with cyclosporine microemulsion (CyA) or tacrolimus (TC). PATIENTS AND METHODS: This prospective study included 81 RT patients divided into two groups according to the CNI: CyA group, n = 35 versus TC group, n = 46. The markers of inflammation (MIF) were determined preRT and at 3 and 12 months' postRT: C-reactive protein (CRP), serum amyloid protein A (SAA), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and pregnancy-associated plasma protein A (PAPP-A). Samples were collected in stable patients in the absence of rejection, active infection, or inflammatory processes. RESULTS: No significant differences existed between the markers of inflammation in the two treatment groups prior to transplantation. At 3 months' posttransplant, patients treated with CyA showed significantly higher levels of IL-6 (P = .05), SAA (P = .03), and sIL-2R (P = .008) compared with patients treated with TC. These differences were maintained for IL-6 (P = .03) and sIL-2R (P = .027) at 12 months' posttransplant. A multivariate analysis at 3 months showed that only age [OR 10.1; CI (95% 2.6-38.4); P = .001], SAA [OR 4.8; IC (95% 1.4-16.5); P = .015], and sIL-2R [OR 4.9; IC (95% 1.5-16.2); P = .009] were independent predictors of the CNI used. At 12 months, age [OR 3.7; IC (95% 0.9-14.2] and sIL-2R [OR 6.04; IC (95% 1.5-23); P = .006] continued to be independent predictors. CONCLUSIONS: Patients treated with CyA displayed significantly higher levels of inflammatory markers (IL-6, SAA, sIL-2R) at 3 and 12 months' posttransplantation, independent of age, gender, time on dialysis, diabetes mellitus (preRT and de novo postRT), and renal function measured by serum creatinine.

Atorvastatin treatment in the short term: does it induce renoprotection or vasculoprotection in renal transplantation?

INTRODUCTION: Proteinuria and dyslipidemia are nonimmune risk factors implicated in the deterioration of kidney function and associated with an increased risk of accelerated atherogenesis. Statin therapy, used for cholesterol reduction, has shown a renoprotective effect in animal models, particularly in cases of proteinuria. This may occur through lipid-independent mechanisms, such as improved endothelial dysfunction/vascular biology, reduced inflammatory cytokine production (transforming growth factor-beta 1 [TGF-beta1]), and regulation of fibrogenic responses. We studied mechanisms of action of agents, such as statins, to change proteinuria, inflammatory parameters, and TGF-beta1 plasma levels in relation to vascular tone. METHODS: Fifty-six kidney transplant recipients (30 men and 26 women of overall mean age 54 +/- 13 years) were treated posttransplantation with atorvastatin (10 mg/d) for 12 weeks without renin-angiotensin-system blockade drugs. Inflammatory variables, biochemical parameters, lipid profile, renal function, and TGF-beta1 levels were determined at baseline and at 3 months. Vascular stiffness was evaluated using pulse wave velocity (PWV). RESULTS: Baseline TGF-beta1 plasma levels were higher among transplant recipients than healthy controls, namely 8.12 ng/mL (range, 5.82-13.12) to 2.55 (range, 1.78- 4.35) (P < .01). Furthermore, the levels remained higher after the treatment with atorvastatin, namely, 7.59 (range, 4.97-12.35) to 2.55 (range, 1.78-4.35) ng/mL (P < .01). Atorvastatin treatment significantly decreased total cholesterol as well as low-density lipoprotein cholesterol plasma levels, but did not modify mean blood pressure (MBP), proteinuria, creatinine clearance, or inflammatory factors. Reduction in TGF-beta1 plasma levels was statistically significant among patients with PWV >9.75 (m/s) (pathology reference value) namely, from 10.7 ng/mL (range, 7.02-13.98) to 6.7 (range, 3.96-11.94) (P = .038). Among older patients, atorvastatin significantly decrease TGF-beta1 plasma levels: from 9.5 ng/mL (range, 6.45-14.44) to 5.65 (range, 3.63-9.48; P < .05). The decreased TGF-beta1 was not related to changes in lipid profiles. CONCLUSIONS: Atorvastatin (10 mg/d) improved the lipid profile and moreover among older patients with worse PWV (>9.75 m/s), TGF-beta1 levels were significantly reduced. Our results suggested that statins displayed potent actions distinct from their hypolipidemic effects.