Pragmatic diagnostic and therapeutic algorithms to optimize new potassium binder use in cardiorenal disease.

BACKGROUND: Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia. METHODS: A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting. RESULTS: Two dedicated pragmatic algorithms are proposed. The lowest intervention threshold (i.e. 5.1 mmol/L or greater) was the one used in the patiromer and sodium zirconium cyclosilicate) pivotal trials, both drugs being indicated to treat hyperkalaemia in a non -emergent setting. Acknowledging the heterogeneity across specialty guidelines in hyperkalaemia definition and thresholds to intervene when facing hyperkalaemia, we have been mindful to use soft language i.e. "it is to consider", not necessarily "to do". CONCLUSIONS: Providing the clinical community with pragmatic algorithms may help optimize the management of high-risk patients by avoiding the risks of both hyper and hypokalaemia and of suboptimal RAASi therapy.

Chronic ozone exposure preferentially modifies root rather than foliar metabolism of date palm (Phoenix dactylifera) saplings.

In their natural environment, date palms are exposed to chronic atmospheric ozone (O3) concentrations from local and remote sources. In order to elucidate the consequences of this exposure, date palm saplings were treated with ambient, 1.5 and 2.0 times ambient O3 for three months in a free-air controlled exposure facility. Chronic O3 exposure reduced carbohydrate contents in leaves and roots, but this effect was much stronger in roots. Still, sucrose contents of both organs were maintained at elevated O3, though at different steady states. Reduced availability of carbohydrate for the Tricarboxylic acid cycle (TCA cycle) may be responsible for the observed reduced foliar contents of several amino acids, whereas malic acid accumulation in the roots indicates a reduced use of TCA cycle intermediates. Carbohydrate deficiency in roots, but not in leaves caused oxidative stress upon chronic O3 exposure, as indicated by enhanced malonedialdehyde, H2O2 and oxidized glutathione contents despite elevated glutathione reductase activity. Reduced levels of phenolics and flavonoids in the roots resulted from decreased production and, therefore, do not indicate oxidative stress compensation by secondary compounds. These results show that roots of date palms are highly susceptible to chronic O3 exposure as a consequence of carbohydrate deficiency.

Exploring new strategies for ozone-risk assessment: A dynamic-threshold case study.

Tropospheric ozone is a dangerous atmospheric pollutant for forest ecosystems when it penetrates stomata. Thresholds for ozone-risk assessment are based on accumulated stomatal ozone fluxes such as the Phytotoxic Ozone Dose (POD). In order to identify the effect of ozone on a Holm oak forest in central Italy, four flux-based ozone impact response functions were implemented and tested in a multi-layer canopy model AIRTREE and evaluated against Gross Primary Productivity (GPP) obtained from observations of Eddy Covariance fluxes of CO2. To evaluate if a clear phytotoxic threshold exists and if it changes during the year, six different detoxifying thresholds ranging between 0 and 5 nmol O3 m-2 s-1 were tested. The use of species-specific rather than more general response functions based on plant functional types (PFT) increased model accuracy (RMSE reduced by up to 8.5%). In the case of linear response functions, a threshold of 1 nmol m-2 s-2 produced the best results for simulations of the whole year, although the tolerance to ozone changed seasonally, with higher tolerance (5 nmol m-2 s-1 or no ozone impact) for Winter and Spring and lower thresholds in Summer and Fall (0-1 nmol m-2 s-1). A "dynamic threshold" obtained by extracting the best daily threshold values from a range of different simulations helped reduce model overestimation of GPP by 213 g C m-2 y-1 and reduce RMSE up to 7.7%. Finally, a nonlinear ozone correction based on manipulative experiments produced the best results when no detoxifying threshold was applied (0 nmol O3 m-2 s-1), suggesting that nonlinear functions fully account for ozone detoxification. The evidence of seasonal changes in ozone tolerance points to the need for seasonal thresholds to predict ozone damage and highlights the importance of performing more species-specific manipulative experiments to derive response functions for a broad range of plant species.

Ten-Year Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant: A Prospective Cohort Study.

Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.

Descriptive study of the general practitioners' perception of direct oral anticoagulants and the risk of genital bleeding in women of childbearing age.

AIM OF THE STUDY AND PATIENTS: Direct oral anticoagulants (DOA) tend to replace antivitamins K (VKA). The incidence of major and minor hemorrhages is higher in women, a difference potentially linked to genital hemorrhages. The objective is to assess the practices and perception of general practitioners of the use of oral anticoagulant therapy in women of childbearing age. MATERIALS AND METHODS: Descriptive, observational, transversal and monocentric study. An 11-items questionnaire was sent to 900 randomized general practitioners, assessing the type of patient, the type of anticoagulant prescribed, the management of genital bleeding, and the assessment of the quality of life of anticoagulated patients. RESULTS: DOA were the most prescribed anticoagulants. Genital hemorrhage was the second leading cause of minor hemorrhage. Most doctors (60.6%) believed they were due to VKAs. 25% reported an alteration in the quality of life of patients following these genital hemorrhages and 47.5% addressed this subject in consultation. CONCLUSION: Our study suggests that, according to the general practitioners interviewed, genital hemorrhage is more frequent on VKA than on DOA in women of reproductive age, which is contradictory with the data in the literature. The probably taboo subject is rarely mentioned in consultation and is responsible for a deterioration in the quality of life in these young patients. No recommendation exists on the management of this type of genital hemorrhage in these women. An algorithm is proposed for their management.

Toward stomatal-flux based forest protection against ozone: The MOTTLES approach.

European standards for the protection of forests from ozone (O3) are based on atmospheric exposure (AOT40) that is not always representative of O3 effects since it is not a proxy of gas uptake through stomata (stomatal flux). MOTTLES "MOnitoring ozone injury for seTTing new critical LEvelS" is a LIFE project aimed at establishing a permanent network of forest sites based on active O3 monitoring at remote areas at high and medium risk of O3 injury, in order to define new standards based on stomatal flux, i.e. PODY (Phytotoxic Ozone Dose above a threshold Y of uptake). Based on the first year of data collected at MOTTLES sites, we describe the MOTTLES monitoring station, together with protocols and metric calculation methods. AOT40 and PODY, computed with different methods, are then compared and correlated with forest-health indicators (radial growth, crown defoliation, visible foliar O3 injury). For the year 2017, the average AOT40 calculated according to the European Directive was even 5 times (on average 1.7 times) the European legislative standard for the protection of forests. When the metrics were calculated according to the European protocols (EU Directive 2008/50/EC or Modelling and Mapping Manual LTRAP Convention), the values were well correlated to those obtained on the basis of the real duration of the growing season (i.e. MOTTLES method) and were thus representative of the actual exposure/flux. AOT40 showed opposite direction relative to PODY. Visible foliar O3 injury appeared as the best forest-health indicator for O3 under field conditions and was more frequently detected at forest edge than inside the forest. The present work may help the set-up of further long-term forest monitoring sites dedicated to O3 assessment in forests, especially because flux-based assessments are recommended as part of monitoring air pollution impacts on ecosystems in the revised EU National Emissions Ceilings Directive.

Ozone-induced stomatal sluggishness changes stomatal parameters of Jarvis-type model in white birch and deciduous oak.

Stomatal ozone flux is closely related to ozone injury to plants. Jarvis-type multiplicative model has been recommended for estimating stomatal ozone flux in forest trees. Ozone can change stomatal conductance by both stomatal closure and less efficient stomatal control (stomatal sluggishness). However, current Jarvis-type models do not account for these ozone effects on stomatal conductance in forest trees. We examined seasonal course of stomatal conductance in two common deciduous tree species native to northern Japan (white birch: Betula platyphylla var. japonica; deciduous oak: Quercus mongolica var. crispula) grown under free-air ozone exposure. We innovatively considered stomatal sluggishness in the Jarvis-type model using a simple parameter, s, relating to cumulative ozone uptake (defined as POD: phytotoxic ozone dose). We found that ozone decreased stomatal conductance of white birch leaves after full expansion (-28%). However, such a reduction of stomatal conductance by ozone fell in late summer (-10%). At the same time, ozone reduced stomatal sensitivity of white birch to VPD and increased stomatal conductance under low light conditions. In contrast, in deciduous oak, ozone did not clearly change the model parameters. The consideration of both ozone-induced stomatal closure and stomatal sluggishness improved the model performance to estimate stomatal conductance and to explain the dose-response relationship on ozone-induced decline of photosynthesis of white birch. Our results indicate that ozone effects on stomatal conductance (i.e. stomatal closure and stomatal sluggishness) are crucial for modelling studies to determine stomatal response in deciduous trees, especially in species sensitive to ozone.

Effects of different routes of application on ethylenediurea persistence in tobacco leaves.

Ethylenediurea (EDU) is a common research tool for investigating ozone impacts on vegetation, although the role of different application routes (foliar spray vs soil drench) on EDU persistence in the leaves is unknown. We quantified EDU concentrations in leaves of the O3-sensitive Bel-W3 cultivar of tobacco treated with EDU as either foliar spray or soil drench. Foliar EDU concentrations were measured by Q-TOF LC/MS. When EDU was applied as foliar spray, 1 h was enough for reaching a measurable concentration within the leaf. EDU concentration increased over the 21-day period when the leaf was not washed after the application (treatment #1), while it decreased when the leaf was washed after the application (treatment #2). These results suggest that: a) dry deposition of EDU onto the leaf surface was gradually absorbed into the unwashed leaf, although the mechanisms of such uptake were unclear; b) concentration of EDU was decreased quickly (-35%) during the first 24 h from application and more slowly during the following three days (-20%) in the washed leaves. Degradation did not involve enzymatic reactions and was not affected by the presence of ROS. When EDU was applied as soil drench, foliar concentrations increased over time, likely due to adsorption onto soil organic matter and gradual re-solubilization by irrigation water. An analysis of EDU concentration in protoplast and intercellular washing fluid showed that EDU did not enter the cells, but was retained in the apoplast only. Possible implications of EDU in the apoplast and recommendations for EDU application are discussed.

BVOC responses to realistic nitrogen fertilization and ozone exposure in silver birch.

Emission of BVOC (Biogenic Volatile Organic Compounds) from plant leaves in response to ozone exposure (O3) and nitrogen (N) fertilization is poorly understood. For the first time, BVOC emissions were explored in a forest tree species (silver birch, Betula pendula) exposed for two years to realistic levels of O3 (35, 48 and 69 ppb as daylight average) and N (10, 30 and 70 kg ha(-1) yr(-1), applied weekly to the soil as ammonium nitrate). The main BVOCs emitted were: α-pinene, ß-pinene, limonene, ocimene, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and hexanal. Ozone exposure increased BVOC emission and reduced total leaf area. The effect on emission was stronger when a short-term O3 metric (concentrations at the time of sampling) rather than a long-term one (AOT40) was used. The effect of O3 on total leaf area was not able to compensate for the stimulation of emission, so that responses to O3 at leaf and whole-plant level were similar. Nitrogen fertilization increased total leaf area, decreased α-pinene and ß-pinene emission, and increased ocimene, hexanal and DMNT emission. The increase of leaf area changed the significance of the emission response to N fertilization for most compounds. Nitrogen fertilization mitigated the effects of O3 exposure on total leaf area, while the combined effects of O3 exposure and N fertilization on BVOC emission were additive and not synergistic. In conclusion, O3 exposure and N fertilization have the potential to affect global BVOC via direct effects on plant emission rates and changes in leaf area.

Effects of long-term ambient ozone exposure on biomass and wood traits in poplar treated with ethylenediurea (EDU).

This is the longest continuous experiment where ethylenediurea (EDU) was used to protect plants from ozone (O3). Effects of long-term ambient O3 exposure (23 ppm h AOT40) on biomass of an O3 sensitive poplar clone (Oxford) were examined after six years from in-ground planting. Trees were irrigated with either water or 450 ppm EDU. Above (-51%) and below-ground biomass (-47%) was reduced by O3 although the effect was significant only for stem and coarse roots. Ambient O3 decreased diameter of the lower stem, and increased moisture content along the stem of not-protected plants (+16%). No other change in the physical wood structure was observed. A comparison with a previous assessment in the same experiment suggested that O3 effects on biomass partitioning to above-ground organs depend on the tree ontogenetic stage. The root/shoot ratios did not change, suggesting that previous short-term observations of reduced allocation to tree roots may be overestimated.

Gene expression in snapbeans exposed to ozone and protected by ethylenediurea.

Ethylenediurea (EDU) is the most common chemical used to prevent ozone (O3) injury on vegetation. Despite considerable research, its mode of action remains elusive and gene expression has not been studied. Transcripts of major antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase) were measured for the first time in a model plant (Phaseolus vulgaris cv S156) after short-term O3 exposure (0 or 90 ppb, 5 h/d, 4 days) and a single spray with EDU (0 or 300 ppm). Visible, physiological and biochemical parameters were assessed as indices of O3-induced stress. In O3-exposed EDU-protected plants, levels of transcript, enzyme activity, H2O2 accumulation, gas exchange and foliar visible injury were similar to those in control plants. These results suggest that EDU may halt the O3-induced ROS generation within 24 h from the exposure, and thus the downstream cascade mechanisms leading to increased H2O2 production, impaired gas exchange, and occurrence of leaf lesions.

Ultrasound findings in dual kidney transplantation.

PURPOSE: This study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT). MATERIALS AND METHODS: We reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55-82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function. RESULTS: Three patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (p<0.01) than SKTs. CONCLUSIONS: CDUS provides useful information in patients with DKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.

Physiological and biochemical responses of Quercus pubescens to air warming and drought on acidic and calcareous soils.

The drought- and thermo-tolerant Quercus pubescens, a tree species growing on both acidic and calcareous soils in the sub-Mediterranean region, was exposed to soil drought (-60% to -80% soil water content) and air warming (+1.2 °C daytime temperature), singly and in combination. The experiment was conducted on two natural forest soils with similar texture but different pH (acidic and calcareous soils). The physiological (photosynthesis) and biochemical (antioxidant system) responses of Q. pubescens were investigated. On acidic soil, Q. pubescens had a higher reactive oxygen species (ROS) content than on calcareous soil, confirming that this species is better adapted to the latter soil type. A down-regulation of ascorbate-glutathione cycle enzymes suggests that ROS were used as signalling molecules. Air warming stimulated stomatal opening, while soil drought induced stomatal closure in the late afternoon and reduced Rubisco carboxylation efficiency. Photosynthetic performance in the combined treatment was higher than under single drought stress and similar to control and air warming. Q. pubescens biochemical responses depended on soil pH. On acidic soil, Q. pubescens trees exposed to air warming used ROS as signalling molecules. On calcareous soil, these trees were able to balance both soil drought and air warming stress, avoiding ROS toxic effects by increasing antioxidant enzyme activitiy and maintaining a high enzymatic antioxidant defence. When combined, drought and air warming induced either more severe (higher oxidative pressure and impairment of the light-harvesting complex) or different responses (decline of the thermal energy dissipation capacity) relative to the single stressors. Overall, however, Q. pubescens preserved the functionality of the photosynthetic apparatus and controlled the antioxidant system response, thus confirming its drought and thermo-tolerance and therefore its potential to adapt to the ongoing climate change.

Is early use of pacifier a risk factor for diarrhea?

AIM: Non nutritive suckling has been always used by mothers for calming and comforting infants and young children. Previous studies have suggested that pacifiers may get contaminated but only three studies have shown a possible association between the use of pacifiers and diarrhea or enteric infections. The goal of this study was to investigate whether the early start of pacifier within the first month of life is a risk factor for diarrhea in early childhood. METHODS: Case-control study. Subjects 12 to 36 month old were recruited. Cases were children with at least 1 episode of diarrhea per year of life. RESULTS: Among cases (N.=63), those who had started using pacifier in the first month of life were 61.9%, while among controls (N.=78) they were 29.4%, OR 3.89, CI95% 1.92-7.85. Type and frequency of pacifier hygiene practices were not associated with diarrhea. CONCLUSION: Our results suggest that the recommendation to postpone pacifier use after the first month of life not to interfere with the duration of breastfeeding, may have also the effect to reduce the risk of episodes of diarrhea in the first three years of life.

Forests under climate change and air pollution: gaps in understanding and future directions for research.

Forests in Europe face significant changes in climate, which in interaction with air quality changes, may significantly affect forest productivity, stand composition and carbon sequestration in both vegetation and soils. Identified knowledge gaps and research needs include: (i) interaction between changes in air quality (trace gas concentrations), climate and other site factors on forest ecosystem response, (ii) significance of biotic processes in system response, (iii) tools for mechanistic and diagnostic understanding and upscaling, and (iv) the need for unifying modelling and empirical research for synthesis. This position paper highlights the above focuses, including the global dimension of air pollution as part of climate change and the need for knowledge transfer to enable reliable risk assessment. A new type of research site in forest ecosystems ("supersites") will be conducive to addressing these gaps by enabling integration of experimentation and modelling within the soil-plant-atmosphere interface, as well as further model development.

Regression of left ventricular hypertrophy in kidney transplant recipients: the potential role for inhibition of mammalian target of rapamycin.

Left ventricular hypertrophy (LVH) contributes to elevated cardiac mortality with graft function in renal transplant recipients. Antihypertensive therapy, and especially angiotensin-converting enzyme (ACE) inhibitors, proved to be effective in regressing the LVH of renal transplant recipients, at least in part by interacting with immunosuppressive agents, thus raising the possibility that immunosuppressive therapy might affect changes in the left ventricular mass (LVM) of recipients. This review mainly focuses on the potential role of mammalian target of rapamycin (mTOR) inhibition to regress cardiac hypertrophy in both experimental models and in the clinical setting. We comment on the results of experimental studies conducted on animal models, which showed regression of cardiac hypertrophy by sirolimus (SRL). We also discuss clinical studies that show that conversion from calcineurin inhibitors to SRL is effective to achieve regression of LVH in both kidney and cardiac transplant recipients, mainly by reducing the true left ventricular wall hypertrophy.

Impact of tissue harmonic imaging on measurement of nuchal translucency thickness.

OBJECTIVES: To evaluate the effect of tissue harmonic imaging (THI) on the measurement of fetal nuchal translucency thickness (NT). METHODS: One-hundred and three pregnant women underwent first-trimester NT measurement according to The Fetal Medicine Foundation criteria. NT was evaluated using conventional ultrasonography (CUS) and THI without modifying any other ultrasound parameter (e.g. gain). For each patient three images with CUS and three images with THI were stored and then measured independently on the ultrasound system by two different operators. The maximum measurements using CUS and THI were compared. Differences between the values of CUS and THI NT measurements were tested using the Wilcoxon signed-rank test. Bland-Altman plots were constructed, and intraobserver and interobserver variabilities were assessed by calculation of the intraclass correlation coefficient. Probability values of < 0.05 were considered significant. RESULTS: Mean maternal age was 32.8 (range, 20-42) years, mean gestational age at examination was 12 + 1 (11 + 0 to 13 + 6) weeks and mean crown-rump length (CRL) was 55.8 (SD, 7.2) mm. Median fetal NT was 1.4 (0.8-3.5) mm using CUS and 1.2 (0.6-3.3) mm using THI (P < 0.001) for the first operator. A second operator remeasured the first 51 cases: median fetal NT was 1.4 (0.8-3.8) mm using CUS and 1.1 (0.6-3.1) mm using THI (P < 0.001). Fetal NT measurements were above the expected median value according to CRL in 49 cases (47.6%) using CUS and in only 24 cases (23.3%) using THI. CONCLUSIONS: THI leads to a small, but significant, reduction of the NT measurement and this could reduce the sensitivity of screening for Down syndrome.

Advances of air pollution science: from forest decline to multiple-stress effects on forest ecosystem services.

Over the past 20 years, the focus of forest science on air pollution has moved from forest decline to a holistic framework of forest health, and from the effects on forest production to the ecosystem services provided by forest ecosystems. Hence, future research should focus on the interacting factorial impacts and resulting antagonistic and synergistic responses of forest trees and ecosystems. The synergistic effects of air pollution and climatic changes, in particular elevated ozone, altered nitrogen, carbon and water availability, must be key issues for research. Present evidence suggests air pollution will become increasingly harmful to forests under climate change, which requires integration amongst various stressors (abiotic and biotic factors, including competition, parasites and fire), effects on forest services (production, biodiversity protection, soil protection, sustained water balance, socio-economical relevance) and assessment approaches (research, monitoring, modeling) to be fostered.

Why and how terrestrial plants exchange gases with air.

This work is intended as a review of gas exchange processes between the atmosphere and the terrestrial vegetation, which have been known for more than two centuries since the discovery of photosynthesis. The physical and biological mechanisms of exchange of carbon dioxide, water vapour, volatile organic compounds emitted by plants and air pollutants taken up by them, is critically reviewed. The role of stomatal physiology is emphasised, as it controls most of these processes. The techniques used for measurement of gas exchange fluxes between the atmosphere and vegetation are outlined.

Reducing the risk of left ventricular hypertrophy in kidney transplant recipients: the potential role of mammalian target of rapamycin.

Persistence of left ventricular hypertrophy (LVH) following renal transplantation is associated with unfavorable outcomes in renal transplant recipients. This review presents clinical data on LVH after renal transplantation and the role of antihypertensive therapy, especially ACE inhibitors, to reduce left ventricular mass, as well as the effects of interactions between antihypertensive medications acting on the renin-angiotensin system and immunosuppressive agents to regress LVH among renal transplant recipients. The effectiveness of sirolimus (SRL) to reduce posttransplantation LVH is also discussed in light of both animal model studies and 2 clinical trials in transplant recipients that showed the efficacy of this immunosuppressive agent to treat LVH in both kidney and heart transplant recipients.