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Due to the global urgency produced by the Covid-19 pandemic, the development of alternative, viable processes, accessible through low-cost and technological resources, became more than necessary. Such is the case of telemedicine which, since its appearance towards the end of the 1960s through telephone consultations, has been transformed according to technological development. Information and communication technologies currently allow the provision of information and medical care services in diverse and distant locations, which is why it turns out to be relevant in the case of the current pandemic. This review work is aimed at examining the current state of the scope in the use of telemedicine that occurred during the current Covid-19 pandemic, its link in the case of medical education in various realities; as well as the analysis, evaluation and proposals on the benefits and concomitant challenges regarding telemedicine in the future.

The closure of universities in the year caused by the pandemic that originated the COVID- determined the Peruvian government to impose distance The closure of the universities in the year caused by the pandemic that originated the COVID determined the Peruvian government to impose distance education. This required the enactment of regulations to ensure continuity of services and access to quality education adaptable to the distance learning modality. However, the psychosocial learning environment of this study modality has a social structure that differs from that of a face-to-face class, which could have a considerable impact on learning outcomes and therefore on students' academic satisfaction. For this reason, the objective of the study was to determine the relationship between the psychosocial learning environment of distance education and the academic satisfaction of graduate students during the pandemic. The methodology used was a quantitative approach with correlational design. The sample consisted of The sample consisted of graduate students of a public university, who were administered two questionnaires; the first to measure their perception of the psychosocial factors affecting their psychosocial learning environment of distance education during the pandemic, using the Sp-DELES scale; and the second to measure academic satisfaction using the SA scale.

La presente obra es fruto del trabajo académico de un equipo de docentes investigadores de varias universidades del Perú, quienes, en el contexto de la disminución de las brechas sociales y educativas del país, y la implementación de nuevas metodologías que permitan que los estudiantes sean cada vez más conscientes de las necesidades de sus comunidades, plantean diversos contenidos y propuestas enmarcados en el Aprendizaje – Servicio en la educación superior universitaria. En este sentido, el capítulo “Educación superior en contextos actuales”, relata la importancia de la responsabilidad social universitaria, la cual surge como tal, en el área empresarial a partir de la preocupación por la sostenibilidad, los derechos humanos, los derechos laborales y la corrupción. La responsabilidad social universitaria está enfocada no sólo en los impactos que la universidad realiza con su misión, sino también en lo que provoca de manera indirecta; es decir, los efectos colaterales. Al respecto, se recomienda que la universidad como parte de su responsabilidad social, propicie el desarrollo óptimo de su entorno y n potencie los beneficios que son cuantificables a través de indicadores. Se debe tener en cuenta que una institución educativa.

Introduction There is an increased risk of thrombotic complications in patients with COVID‐19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new‐onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID‐19. Methods We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow‐up due to kidney transplantation or death from non‐thrombotic causes. Findings One‐hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS‐CoV‐2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID‐19 survivors compared to the non‐infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow‐up of 7 months. Multivariate regression analysis showed that COVID‐19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5–280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events. Conclusions There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID‐19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID‐19.

Objective: This article, of a theoretical nature, was oriented to the contextual analysis referred to digital government, its origin, aspects, and trends; mainly, the way in which it was implemented and developed in some Latin American countries was emphasized, in addition to the reflections on the implications related to digital government in the current situation, as well as the challenges it has been facing and future challenges. Theoretical framework: The universe of more contemporary aspects regarding electronic government was explored from the perspective of state management, as well as the foundations on which it has been consolidating and the changes it has undergone and at the same time generated in its wide spectrum of applications. Design/Methodology/Approach: A descriptive systematic review has been implemented with the collection of various definitions, approaches and strategies in relation to electronic government. Based on the qualitative approach, the analysis and extraction of various articles with relevant information from various databases such as Scopus, Ebsco, ProQuest and Scielo was carried out; taking into account those of the last four years. Findings: The acceptance of electronic government processes was based on the characteristics of citizens and their attitude towards technology; public bodies continue to show a series of problems, among which a marked inability to resolve the duties effectively and efficiently in charge despite having the appropriate technological tools and implements stands out. Research, practical and social implications: Future efforts that seek not only electronic government, but also a scaffolding that supports the development of administration processes through TIC and new platforms based on artificial intelligence. Implications/Originality/Value: The real implementation of an electronic government requires, urges and forces cultural changes in society due to the use of TIC and cutting-edge technological resources.

Resumen: Una buena gestión y calidad de la Formación Sanitaria Especializada (FSE) exige el compromiso explícito de los responsables de las CCAA y de los centros sanitarios. Esto implica la acreditación y reconocimiento de tutores, desarrollar el marco normativo que establece el RD 183/2008 (a los nueve años de su publicación sólo Cataluña, Canarias, Castilla y León, Extremadura, La Rioja y el País Vasco, lo han hecho), una mención explícita de la FSE en los planes estratégicos de las organizaciones sanitarias y en los contratos-programa con las unidades docentes y una participación activa de los jefes de estudio en los consejos de dirección de los centros. Por parte del Ministerio de Sanidad, es preciso agilizar la acreditación de las nuevas unidades docentes y abordar, junto con las CCAA, los problemas de financiación del proyecto de troncalidad y la organización de las unidades docentes troncales. Respecto al sentido de la formación, esta se ha de centrar en la seguridad del paciente, aquí la simulación es una metodología formativa idónea, y en la humanización, con una práctica de la medicina bajo un modelo deliberativo, siendo los formadores ejemplo para los que aprenden. Abstract: The commitment of the heads of the Autonomous Communities and the health centers is key to a good management and the quality of the Specialized Healthcare Training (SHT). This implies the accreditation and recognition of tutors, developing the regulatory framework established by Royal Decree 183/2008 (nine years after its publication, only Catalonia, the Canary Islands, Castilla y León, Extremadura, La Rioja and the Basque Country have done so), an explicit mention of the SHT in the strategic plans of the health organizations and an active participation of the heads of SHT in the boards of directors. On the part of the Ministry of Health, it is necessary to speed up the accreditation process of new teaching units and, together with the Autonomous Communities, and address the financing problems of the core curriculum project and the organization of the core teaching units. Regarding the sense of training, this has to focus on safety patient, here the simulation is a suitable training methodology, and in the humanization, with a practice of medicine under a deliberative model, being the trainers an example for those who learn. Palabras clave: Acreditación unidades docentes, Acreditación tutores, Formación sanitaria especializada, Simulación, Seguridad del paciente, Educación centrada en el paciente, Keywords: Accreditation teaching units, Tutor accreditation, Postgraduate medical education, Specialized training, Simulation, Safety patient, Patient-centred education

Background and Aims There is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19. Method We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes. Results 185 prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was 38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the follow-up period. The median time from diagnosis of SARS-CoV-2 to the first thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-CoV-2 compared to non-infected patients (see Figure 1). Mean survival from thrombotic event was 6.1±0.4 months in the COVID-infected group, compared to 6.97±0.04 months in the non-infected group (p Conclusion There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

This research has been funded by Junta de Andalucía (Spain) under project B-TIC-468- UGR18. The project was partially supported by European Regional Development Funds (ERDF)., In skiing it is important to know how the skier accelerates and inclines the skis during the turn to avoid injuries and improve technique. The purpose of this pilot study with three participants was to develop and evaluate a compact, wireless, and low-cost system for detecting the inclination and acceleration of skis in the field based on inertial measurement units (IMU). To that end, a commercial IMU board was placed on each ski behind the skier boot. With the use of an attitude and heading reference system algorithm included in the sensor board, the orientation and attitude data of the skis were obtained (roll, pitch, and yaw) by IMU sensor data fusion. Results demonstrate that the proposed IMU-based system can provide reliable low-drifted data up to 11 min of continuous usage in the worst case. Inertial angle data from the IMU-based system were compared with the data collected by a video-based 3D-kinematic reference system to evaluate its operation in terms of data correlation and system performance. Correlation coefficients between 0.889 (roll) and 0.991 (yaw) were obtained. Mean biases from -1.13 degrees (roll) to 0.44 degrees (yaw) and 95% limits of agreements from 2.87 degrees (yaw) to 6.27 degrees (roll) were calculated for the 1-min trials. Although low mean biases were achieved, some limitations arose in the system precision for pitch and roll estimations that could be due to the low sampling rate allowed by the sensor data fusion algorithm and the initial zeroing of the gyroscope., Junta de Andalucia European Commission B-TIC-468UGR18, European Commission

Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) were collected. The evolution of renal function, proteinuria and lipid profile was analyzed during the 1-year follow-up. The cohort included 76 patients (68% male, mean age 66 ± 10 years). The mean baseline creatinine was 1.55 ± 0.77 mg/dL, and the mean eGFR was 52 ± 22 mL/min/1.73 m2. Reductions in LDL-cholesterol, total cholesterol and triglycerides during the first month were 51 ± 25%, 32 ± 25% and 11 ± 40%, respectively, levels that remained stable throughout the first year (p &lt, 0.001 for LDL-cholesterol and total cholesterol trends and p = 0.002 for triglyceride trend). During follow-up, proteinuria improved from 57 (9–481) to 30 (7–520) mg/g (p = 0.021). In addition, eGFR remained stable, and no adverse events were reported. In our cohort, dyslipidemia treatment with PCSK9i was associated with decreased proteinuria in CKD patients, an effect that might be due to reduced lipid nephrotoxicity. Clinical trials are needed to further investigate whether this impact on proteinuria can significantly slow CKD progression in the long term.

Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg·day−1 of melatonin or placebo 30 min before bedtime during 4 weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG·GSH−1 and GPx·GRd−1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

Background and objectives Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. Methods From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. Results We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24 ml/min/1.73 m2. Conclusions The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury.

[EN] DELLA proteins are a group of plant specific GRAS proteins of transcriptional regulators that have a key role in gibberellin (GA) signaling. In Arabidopsis, the DELLA family is formed by five members. The complexity of this gene family raises the question on whether single DELLA proteins have specific or overlapping functions in the control of several GA-dependent developmental processes. To better understand the roles played by RGL2, one of the DELLA proteins in Arabidopsis, two transgenic lines that express fusion proteins of Venus-RGL2 and a dominant version of RGL2, YPet-rgl2A17, were generated by recombineering strategy using a genomic clone that contained the RGL2 gene. The dominant YPet-rg12 Delta 17 protein is not degraded by GAs, and therefore it blocks the RGL2-dependent GA signaling and hence RGL2-dependent development. The RGL2 role in seed germination was further confirmed using these genetic tools, while new functions of RGL2 in plant development were uncovered. RGL2 has a clear function in the regulation of flower development, particularly stamen growth and anther dehiscence, which has a great impact in fertility. Moreover, the increased ovule number in the YPet-rg12 Delta 17 line points out the role of RGL2 in the determination of ovule number., We wish to thank Ms. J. Yun,M.A. Argomániz for technical assistance, and the IBMCP microscopy facility. Edit Syndicate (http://www.editsyndicate.com/) provided proofreading of the manuscript. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness-FEDER [BI02011-26302 and BI02014-55946] and Generalitat Valenciana [ACOMP/2013/048 and ACOMP/2014/106] to M.A.P-A. and National Science Foundation [MCB-0923727] to J.M.A. MAP-A. received a fellowship of the 'Salvador de Madariaga' program from Spanish Ministry of Science and Innovation.

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency.

Background/Aim: The levels of C-reactive protein (CRP) have been related to hypoalbuminemia and the necessity of erythropoietin in patients on maintenance hemodialysis. However, in several studies, the patients’ clinical situation is not taken into account. The aim of the present work was to analyze the relationship between CRP and serum albumin and hemoglobin and the erythropoietin resistance index (ERI) in a population of patients on chronic hemodialysis classified according to their clinical situation. Methods: In a cohort of 53 patients followed for 12 months, we analyzed the CRP level and its association with albumin and hemoglobin levels and the ERI (ratio of total weekly erythropoietin dose in units/weight to hemoglobin concentration in g/dl) at the start of the study and at 6 and 12 months thereafter. The patients were divided into three groups based on the presence of inflammatory/infectious disorders during the 4 weeks prior to CRP determination (group A) or the use of a jugular catheter (group B) or an arteriovenous fistula (group C) as vascular access for hemodialysis. Results: At baseline, the CRP levels (47.1 mg/l in group A, 30.7 mg/l in group B, and 9.4 mg/l in group C) and the ERI (23.9 in group A, 24.6 in group B, and 10.7 in group C) were higher in groups A and B than in group C (p < 0.001 for both parameters). Serum albumin (3.9 g/dl in group A, 4.1 g/dl in group B, and 4.4 g/dl in group C) and hemoglobin (10.4 g/dl in group A, 11.3 g/dl in group B, and 12 g/dl in group C) were lower in groups A and B than in group C (p < 0.05 for serum albumin and p < 0.01 for hemoglobin). In all patients, the baseline CRP level correlated with the albumin level (r = –0.3853, p < 0.01), with the hemoglobin level (r = –0.2950, p < 0.05), and with the ERI (r = 0.4378, p < 0.01). However, if we only considered the group C patients, there was no correlation between baseline CRP and albumin, hemoglobin, and ERI. Similar results were observed at 6 and 12 months. Conclusions: The CRP, albumin, and hemoglobin levels and the ERI mostly depend on the existence of ongoing inflammatory/infectious disorders and the use of a catheter as vascular access. In the absence of these clinical conditions, we could not correlate the CRP level with the other parameters. The relationship between CRP, albumin, and anemia may be an epiphenomenon

Background Although tacrolimus is recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of idiopathic membranous nephropathy (MN), little is known about factors that influence response and relapse of the disease after tacrolimus therapy. Methods Multicentre study that collected 122 MN patients with nephrotic syndrome and stable renal function treated with tacrolimus. Duration of treatment was 17.6 ± 7.2 months, including a full-dose and a tapering period. Results The percentage of remission was 60, 78 and 84% after 6, 12 and 18 months of treatment, respectively. The amount of proteinuria at baseline significantly predicted remission, the lower the baseline proteinuria the higher the probability of remission. Only 10 patients (8%) received concomitantly corticosteroids, and their rate of remission was similar (80% at 18 months). Among responders, 42% achieved complete remission (CR) and 58% partial remission (PR). Almost half (44%) of the responder patients relapsed. The amount of proteinuria at the onset of tacrolimus tapering was significantly higher in relapsing patients. By multivariable analysis, the presence of a PR versus CR at the onset of tacrolimus tapering and a shorter duration of the tapering period significantly predicted relapses. Tolerance was good and the number of adverse events low. Conclusions Tacrolimus monotherapy is an effective and safe option for the treatment of MN with stable renal function. Relapses are frequent in patients with PR and can be partially prevented by a longer tapering period.

Cancer has been reported to be more common among kidney transplant recipients than waiting-list patients or the general population. Use of anticalcineurin agents and azathioprine are relevant risk factors. Nine renal allograft recipients (seven men and two women) of mean age 67.6 (55-77) years and mean time after transplantation of 30.7 (58-216) months were switched to everolimus-based immunosuppression because of the presence of biopsy-proven malignancies (eight patients) or neurological tacrolimus toxicity (one patient). One patient with posttransplant lymphoproliferative disease also received chemotherapy with a good evolution at 6 months. He showed an initial increase in the protein to creatinine ratio (peak 3.3 mg/mg at 3 months) that was controlled by increasing the enalapril dose. One patient with skin cancer and severe atheromatosis (baseline SCr 2.5 mg/dL, creatinine clearance 17 mL/min, and protein to creatinine ratio 3.2 mg/mg), had cyclosporine and everolimus overlapped for 25 days, showing a continued poor evolution requiring dialysis initiation at 3 months after switch. The other six patients with recurrent skin cancers had good cancer evolution, with no new skin tumors and regression of skin lesions in three, including not biopsied actinic keratosis. Sudden switching from calcineurin inhibitors to everolimus is safe and may be used in long-term transplant recipients with malignancies. In patients with advanced chronic nephropathy this approach appeared to be less beneficial.

Background and objectives: We studied the relationship between microinflammation and endothelial damage in chronic kidney disease (CKD) patients on different dialysis modalities. Design, setting, participants, & measurements: Four groups of CKD stage 5 patients were studied: 1) 14 nondialysis CKD patients (CKD-NonD); 2) 15 hemodialysis patients (HD); 3) 12 peritoneal dialysis patients with residual renal function >1 ml/min (PD-RRF >1); and 4) 13 peritoneal dialysis patients with residual renal function ≤1 ml/min (PD-RRF ≤1). Ten healthy subjects served as controls. CD14+CD16+ cells and apoptotic endothelial microparticles (EMPs) were measured by flow cytometry. Serum vascular endothelial growth factor (VEGF) was measured by ELISA. Results: CKD-NonD and HD patients had a higher percentage of CD14+CD16+ monocytes than PD groups and controls. CD14+CD16+ was similar in the PD groups, regardless of their RRF, and controls. The four uremic groups displayed a marked increase in apoptotic EMPs and VEGF compared with controls. Apoptotic EMPs and VEGF were significantly higher in HD patients than in CKD-NonD and both PD groups. However, there were no significant differences between CKD-NonD and the two PD groups. There was a correlation between CD14+CD16+ and endothelial damage in CKD-NonD and HD patients, but not in PD and controls. Conclusions: There was an increase in CD14+CD16+ only in CKD-NonD and HD patients. In these patients, there was a relationship between increased CD14+CD16+ and endothelial damage. These results strongly suggest that other factors unrelated to the microinflammatory status mediated by CD14+CD16+ are promoting the endothelial damage in PD, regardless of their RRF.

Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.

Background. This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. Methods. In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2-L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Results. BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P

Omeprazole is a proton pump inhibitor with a number of pharmacokinetic drug interactions due to interference with cytochrome P450. Some studies show absence of relevant interaction between omeprazole and cyclosporine, but little is known about possible interactions between omeprazole and tacrolimus. In vitro studies suggest such interference, but no clinical data are available so far. We assessed interactions between omeprazole and tacrolimus among patients fulfilling two criteria: (1) renal allograft recipients receiving immunosuppression based on tacrolimus and acid-related disorder prophylaxis with omeprazole 20 mg/d since the day of the transplant procedure and (2) stopped omeprazole when it was considered unnecessary. Fifty-one transplant recipients received concomitant immunosuppression with MMF-prednisone (n = 47) or azathioprine-prednisone (n = 1), or rapamycin-prednisone (n = 2) or only prednisone (n = 1). omeprazole was stopped after 6.2 +/- 3 months of treatment. Tacrolimus doses and levels were recorded during 3 outpatient visits before omeprazole withdrawal (Pre3/Pre2/Pre1), at the withdrawal visit (Susp), and at 3 visits after withdrawal (Pos1/Pos2/Pos3). Weight gain was significant (72.5 +/- 13 kg Pre3; 73.4 +/- 13 kg Susp; 74 +/- 12.9 kg Pos3, P < .0001) and serum creatinine (SCr) decreased (1.70 +/- 0.49 mg/dL Pre3; 1.63 + 0.49 Susp; 1.58 +/- 0.48 Pos3, P < .0001). The progressive decrease in tacrolimus doses and levels was significant (ANOVA including the 7 visits

Osteopenia is a common complication after transplantation. However, prospective long-term studies are scarce and most were performed in patients on cyclosporine and high-dose steroids. In 65 patients with functioning grafts, 41 males and 24 females, 50 on tacrolimus-based immunosuppression and 15 on cyclosporine-based immunosuppression, bone mineral density (BMD) was measured in the lumbar spine (L2-L4) and femoral neck (FN) using dual X-ray absorptiometry (DEXA) in the first month after transplantation (baseline) and at 1, 2, and 3 years. At baseline, BMD was similar to the control population both in L2-L4 (z score = -0.421) and in FN (z score = -0.518). During the follow-up, 3 types of patterns were identified: BMD increased in L2-L4 in 25 patients (38.5%), remained stable in 20 patients (30.8%), and decreased in 20 patients (30.8%). BMD losses appeared mainly during the first year (0.964 +/- 0.162 baseline; 0.904 +/- 0.161 at 1 year, 0.886 +/- 0.140 at 3 years; analysis of variance [ANOVA] P.001). However, the improvement was maintained throughout the follow-up (0.860 +/- 0.176 g/cm2 at baseline; 0.901 +/- 0.161 at 1 year; 0.954 +/- 0.178 at 3 years; ANOVA P.001) and there was a parallel increase of BMD in FN (0.712 +/- 0.144 at baseline; 0.744 +/- 0.249 at 1 year; 0.826 +/- 0.184 at 3 years; ANOVA P.01). There were no differences between both groups in graft function, intact parathyroid hormone (iPTH) levels, number of postmenopausal women, or steroid doses. About one third of patients had bone loss during the first year after transplantation. We were unable to identify any risk factor for this complication in patients on low-dose steroids.

Cyclosporin A (CsA) concentration monitoring with 2 h post-dosing levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The advantages of this policy beyond the first 12 months remain a matter of debate. The purpose of the present work was to evaluate the C2 target ranges on CsA monitoring after the first year in stable kidney transplant patients.We studied 142 patients, 94 on CsA-steroids and 48 on triple therapy (CsA-azathioprin-steroids), transplanted for 104+/-42 months and with a serum creatinine of 1.53+/-0.52 mg/dl. C2 and C0 measurements were performed at baseline and at least twice more during the year of follow-up.The mean annual C2 blood levels in double therapy patients showed C2 in 23 (24.5%) of600 ng/ml; in 53 (56.4%) of between 600 and 850 ng/ml; and in 18 patients (19.1%) of850 ng/ml. In the triple therapy group, C2 in 12 (25%) was500 ng/ml, in 24 (50%) between 500 and 700 ng/ml and in 12 patients (25%)700 ng/ml. In both groups, higher C2 levels were associated with a better absorption of the drug measured by the ratio C2/C0 and C2/dose. There were no differences in incidence of infections, need for hospitalization and the presence of hypertension, hyperuricaemia, hypercholesterolaemia or diabetes between patients with low and high C2 blood levels. However, serum creatinine was higher in triple therapy patients with lower C0 levels (P = 0.004). In 135 patients (90 on double and 45 on triple therapy), renal function remained stable during follow-up and 120 of them (89%) had C2 values under the recommended ranges.C2 monitoring in maintenance patients enabled us to identify overexposure to CsA. Target levels of C2 should be adjusted according to the immunosuppressive regime. C2 levels between 600 and 800 ng/ml in double therapy patients and between 500 and 700 ng/ml in triple therapy patients are sufficient to give an adequate immunosuppression. The superiority of C2 with respect to C0 levels could not be demonstrated.