Forms of nitrogen inputs regulate the intensity of soil acidification.

Soil acidification induced by reactive nitrogen (N) inputs can alter the structure and function of terrestrial ecosystems. Because different N-transformation processes contribute to the production and consumption of H+ , the magnitude of acidification likely depends on the relative amounts of organic N (ON) and inorganic N (IN) inputs. However, few studies have explicitly measured the effects of N composition on soil acidification. In this study, we first conducted a meta-analysis to test the effects of ON or IN inputs on soil acidification across 53 studies in grasslands. We then compared soil acidification across five different ON:IN ratios and two input rates based on long-term field N addition experiments. The meta-analysis showed that ON had weaker effects on soil acidification than IN when the N addition rate was above 20 g N m-2 year-1 . The field experiment confirmed the findings from meta-analysis: N addition with proportions of ON ≥ 20% caused less soil acidification, especially at a high input rate (30 g N m-2 year-1 ). Structural equation model analysis showed that this result was largely due to a relatively low rate of H+ production from ON as NH3 volatilization and uptake of ON and NH4 + by the dominant grass species Leymus chinensis (which are both lower net contributors to H+ production) result in less NH4 + available for nitrification (which is a higher net contributor to H+ production). These results indicate that the evaluation of soil acidification induced by N inputs should consider N forms and manipulations of relative composition of N inputs may provide an effective approach to alleviate the N-induced soil acidification.

Antifungal γ-Pyrone and Isoprenylated Cyclohexanoids from the Fungus Beenakia informis.

Chemical investigation of the extract of the macroscopic fungus Beenakia informis led to the isolation of a previously unreported γ-pyrone and two new isoprenylated cyclohexanoids, together with speciocin N. Their structures were elucidated spectroscopically and the absolute configuration was determined by comparison of the experimental vs. calculated ECD curves. Three of the compounds showed very good to moderate activity against phytopathogenic fungi.

Effect of leaf-to-fruit ratios on phenolic and sensory profiles of Malbec wines from single high-wire-trellised vineyards.

BACKGROUND: The single high-wire system is a free canopy trellis system suitable for warm to hot climates. In a global warming scenario, it arouses as a technological solution since it prevents berry overheating and sunburn. Canopy management practices manipulate leaf-to-fruit ratios, affecting berry and wine composition. We aimed to evaluate the phenolic and sensory profiles of Malbec wines from single high-wire trellised vineyards in a hot region in Mendoza (Argentina) and to assess the effect of varying leaf-to-fruit ratios on these attributes. We manipulated leaf-to-fruit ratios by varying shoot trimming (experiment 1: 0.45 m, 0.80 m, and untrimmed) and winter pruning severity (experiment 2: 16, 24, 32, and >32 countable buds per meter). We characterized wine attributes by a descriptive analysis, color by the CIELAB space, and global phenolics compounds and anthocyanins by high-performance liquid chromatography with diode array detection. RESULTS: We found that wines where shoots were trimmed to 0.80 m or left untrimmed had similar and greater intensity of color, violet hue, astringency, and alcohol and a richer aroma profile than wines where shoots were trimmed to 0.45 m. Meanwhile, wines from 16 and >32 buds/m treatments (the latter simulating a box pruning) were similar to each other and had higher color intensity, violet hue, acidity, alcohol, and astringency and a more complex aroma profile than the other pruning treatments. CONCLUSIONS: The best quality wines were achieved by leaving 16 or >32 buds/m and by trimming shoots to 0.80 m or leaving them untrimmed. The modulation of cultural practices in sprawling canopies offers the potential to produce wines with different styles in hot regions. © 2020 Society of Chemical Industry.

Improving bioreactor production of a recombinant glycoprotein in Escherichia coli: Effect of specific growth rate on protein glycosylation and specific productivity.

In the last decades bacterial glycoengineering emerged as a new field as the result of the ability to transfer the Campylobacter jejuni N- glycosylation machinery into Escherichia coli for the production of recombinant glycoproteins that can be used as antigens for diagnosis, vaccines, and therapeutics. However, the identification of critical parameters implicated in the production process and its optimization to jump to a productive scale is still required. In this study, we developed a dual expression glycosylation vector for the production of the recombinant glycoprotein AcrA-O157, a novel antigen that allows the serodiagnosis of the infection with enterohemorrhagic E. coli O157 in humans. Volumetric productivity was studied in different culture media and found that 2xYP had 6.9-fold higher productivity than the extensively used LB. Subsequently, bioreactor batch and exponential-fed-batch cultures were designed to determine the influence of the specific growth rate (µ) on AcrA-O157 glycosylation efficiency, production kinetics, and specific productivity. At µmax , AcrA glycosylation with O157-polysaccharide and the specific synthesis rate were maximal, constituting the optimal physiological condition for AcrA-O157 production. Our findings should be considered for the design, optimization, and scaling up of AcrA-O157 production and other recombinant glycoproteins attractive for industrial applications.

Metabolites from the Dark Septate Endophyte Drechslera sp. Evaluation by LC/MS and Principal Component Analysis of Culture Extracts with Histone Deacetylase Inhibitors.

Secondary metabolites from the cultures of the dark septate fungal endophyte (DSE) Drechslera sp., isolated from the roots of rye grass (Lollium sp.) and cultured under different experimental conditions, are described here for the first time. The use of suberoylanilidehydroxamic acid (SAHA) and other histone deacetylase inhibitors as epigenetic modifiers in the culture medium was evaluated by LC/MS and LC/MS/MS. Several differences in the metabolite production were detected by means of supervised principal component analysis (PCA) of LC/MS data. The presence of the compounds in the culture medium or in the mycelium was compared. In order to confirm their structure, many of these natural products were isolated from a larger scale culture. These metabolites were characterized as prenylhydroxybenzoic acids and chromans, two compounds, one of each class were previously undescribed, prenylquinoids, diketopiperazines and macrosphelides. Some of the compounds, which were released to the medium, showed good antifungal activity, suggesting that these compounds could protect Lollium from fungal phytopatogens. The use of SAHA as an additive of the cultures also induced the release of hexosylphytosphyngosine to the culture medium. The biotransformation of the inhibitors was observed in addition to the production of antifungal metabolites, showing the ability of this endophytic strain to control xenobiotics.

Watershed vs. within-lake drivers of nitrogen: phosphorus dynamics in shallow lakes.

Research on lake eutrophication often identifies variables affecting amounts of phosphorus (P) and nitrogen (N) in lakes, but understanding factors influencing N:P ratios is important given its influence on species composition and toxin production by cyanobacteria. We sampled 80 shallow lakes in Minnesota (USA) for three years to assess effects of watershed size, proportion of watershed as both row crop and natural area, fish biomass, and lake alternative state (turbid vs. clear) on total N : total P (TN : TP), ammonium, total dissolved phosphorus (TDP), and seston stoichiometry. We also examined N:P stoichiometry in 20 additional lakes that shifted states during the study. Last, we assessed the importance of denitrification by measuring denitrification rates in sediment cores from a subset of 34 lakes, and by measuring seston δ15 N in four additional experimental lakes before and after they were experimentally manipulated from turbid to clear states. Results showed alternative state had the largest influence on overall N:P stoichiometry in these systems, as it had the strongest relationship with TN : TP, seston C:N:P, ammonium, and TDP. Turbid lakes had higher N at given levels of P than clear lakes, with TN and ammonium 2-fold and 1.4-fold higher in turbid lakes, respectively. In lakes that shifted states, TN was 3-fold higher in turbid lakes, while TP was only 2-fold higher, supporting the notion N is more responsive to state shifts than is P. Seston δ15 N increased after lakes shifted to clear states, suggesting higher denitrification rates may be important for reducing N levels in clear states, and potential denitrification rates in sediment cores were among the highest recorded in the literature. Overall, our results indicate lake state was a primary driver of N:P dynamics in shallow lakes, and lakes in clear states had much lower N at a given level of P relative to turbid lakes, likely due to higher denitrification rates. Shallow lakes are often managed for the clear-water state due to increased value as wildlife habitat. However, our results indicate lake state also influences N biogeochemistry, such that managing shallow lakes for the clear-water state may also mitigate excess N levels at a landscape scale.

Pectinase production by Aspergillus giganteus in solid-state fermentation: optimization, scale-up, biochemical characterization and its application in olive-oil extraction.

The application of pectinases in industrial olive-oil processes is restricted by its production cost. Consequently, new fungal strains able to produce higher pectinase titers are required. The aim of this work was to study the capability of Aspergillus giganteus NRRL10 to produce pectinolytic enzymes by SSF and evaluate the application of these in olive-oil extraction. A. giganteus was selected among 12 strains on the basis of high pectinolytic activity and stability. A mixture composed by wheat bran, orange, and lemon peels was selected as the best substrate for enzyme production. Statistical analyses of the experimental design indicated that pH, temperature, and CaCl2 are the main factors that affect the production. Subsequently, different aeration flows were tested in a tray reactor; the highest activity was achieved at 20 L min-1 per kilogram of dry substrate (kgds). Finally, the pectinolytic enzymes from A. giganteus improved the oil yield and rheological characteristics without affecting oil chemical properties.

Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I.

BACKGROUND: As 1,25(OH)2D3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences. CASE DESCRIPTION: An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH)2D3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated. During periods of nonadherence to therapy, chemical measurements revealed detectable FGF-23 levels, with undetectable 1,25(OH)2D3, hypophosphatemia, low tubular reabsorption of phosphate, hypocalcemia, and very elevated parathyroid hormone (PTH) levels. These changes, in addition to elevated RAAS levels, normalized during calcitriol therapy despite elevated FGF-23 levels. At age 12 years, all rachitic manifestations were absent, and bone mineral density (BMD) and the echocardiogram were normal. CONCLUSIONS: Whereas 1,25(OH)2D3 is not indispensable for FGF-23 production, PTH in the absence of vitamin D may maintain FGF-23 secretion despite hypocalcemia. Normalization of urinary phosphate losses despite elevated FGF-23 during calcitriol-mediated suppression of secondary hyperparathyroidism points to a cardinal role of PTH as a cause of the phosphaturia in VDRR-I. Normalization of RAAS by calcitriol may conceivably prevent adverse cardiovascular outcomes.

Characterization, optimization, and scale-up of cellulases production by trichoderma reesei cbs 836.91 in solid-state fermentation using agro-industrial products.

The application of cellulases in saccharification processes is restricted by its production cost. Consequently, new fungal strains able to elaborate higher cellulases titers and with special activity profiles are required to make the process economical. The aim of this investigation was to find a promising wild-type Trichoderma strain for cellulases production. The Trichoderma reesei strain 938 (CBS 836.91) was selected among twenty strains on the basis of cellulase-agar-plate screening. Evaluation of the selected strain on six solid substrates indicated the highest activities to be obtained from wheat bran. Statistical analyses of the experimental design indicated a significant effect of pH and moisture on the generation of endoglucanase (EGA) and filter-paper (FPA) activity. Furthermore, a central-composite design-based optimization revealed that pH values between 6.4 and 6.6 and moisture from 74 to 94% were optimal for cellulases production. Under these conditions, 8-10 IU gds(-1) of FPA and 15.6-17.8 IU gds(-1) of EGA were obtained. In addition, cultivation in a rotating-drum reactor under optimal conditions gave 8.2 IU gds(-1) FPA and 13.5 IU gds(-1) EGA. Biochemical characterization of T. reesei 938 cellulases indicated a substantially higher resistance to 4 mM Fe(+2) and a slightly greater tolerance to alkaline pH in comparison to Celluclast(®). These results suggest that T. reesei 938 could be a promising candidate for improved cellulases production through direct-evolution strategies.

Variation in C:N:S stoichiometry and nutrient storage related to body size in a holometabolous insect (Curculio davidi) (Coleoptera: Curculionidae) larva.

Body size can be an important factor controlling consumer stoichiometry. In holometabolous insects, body size is typically associated with nutrient storage. Consumer stoichiometry is known to vary within species across a range of body sizes; however, the contribution of nutrient storage to this variation is not well understood. We used the fifth-instar larvae of the oak weevil (Coleoptera: Curculio davidi Fairmaire), which is characterized by a high capacity for nutrient storage, to investigate the effect of shifts in nutrient storage with body mass on variations in larva stoichiometry. Our results showed that weevil larvae with larger body mass had a lower carbon (C) content, reflecting decreases in the sequestration rate of C-rich lipids. Larger larvae had elevated concentrations of nitrogen (N), sulfur (S), and protein. The similar patterns of variation in elemental composition and macromolecule storage with body weight indicate that the shift in nutrient storage is the main factor causing the variation in larval stoichiometry with body weight. This finding was further supported by the low variation in residual larval biomass C, N, and S concentrations after lipid extraction. These results help decipher the physiological mechanism of stoichiometric regulation in growing organisms.

Microplate assay for endo-polygalacturonase activity determination based on ruthenium red method.

Endo-polygalacturonase (endo-PGase) activity determinations generally rely on viscosity changes or reducing sugar ends produced by this activity over polygalacturonic acid. Torres and coworkers [Enzyme Microb. Technol. 48 (2011) 123-128] showed that ruthenium red (RR) is useful for endo-PGase determination. In this article, we present a high-throughput liquid-based endo-PGase assay based on the RR method and compare it with the viscosity determination method. The reduced assay uses a small volume of enzyme solution, 40 µg of polygalacturonic acid, and 45 µg of RR for each sample determination. Furthermore, we obtained an interconversion factor for RR and viscosity activities.

Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.

Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.

Calcium complexation by steroids involved in the steroidogenesis.

Steroids that take part in the pathways of human steroidogenesis are involved in many biological mechanisms where they interact with calcium. In the present work, the binding selectivities and affinities for calcium of progestagens, mineralocorticoids, androstagens, and estrogens were studied by Electrospray Ionization-Mass Spectrometry (ESI-MS). The adduct profile of each steroid was characterized by high resolution and tandem mass spectrometry. The relative stability of the most important adducts was studied by threshold collision induced dissociation, E1/2. Doubly-charged steroid-calcium complexes [nM + Ca]2+ with n = 1-6 were predominant in the mass spectra. The adduct [5M + Ca]2+ was the base peak for most 3-keto-steroids, while ligands bearing hindered ketones or α-hydroxy-ketones also yielded [nM + Ca + mH2O]2+ with n = 3-4 and m = 0-1. Principal component analysis allowed us to spot the main differences and similarities in the binding behavior of these steroids. The isomers testosterone and dehydroepiandrosterone, androstanolone and epiandrosterone, and 17-α-hydroxyprogesterone and 11-deoxycorticosterone showed remarkable differences in their adduct profiles. Computational modeling of representative adducts was performed by density functional theory methods. The possible binding modes at low and high numbers of steroid ligands were determined by calcium Gas Phase Affinity, and through modeling of the complexes and comparison of their relative stabilities, in agreement with the experimental results.

Acute atrazine intoxication in heifers: Case report and toxicological studies.

Atrazine is a triazine organochloride herbicide, frequently used in different agricultural activities. Rare acute intoxication with atrazine is reported in production animals, and its metabolism in mammals is unknown. We report a spontaneous case of atrazine acute intoxication in 16.1% animals of a 168-beef heifer herd exposed to the herbicide at a farm located in Buenos Aires province, Argentina. Affected heifers showed different neurological signs and died suddenly, similar to the previous natural atrazine intoxication report. During autopsy, no gross lesions were observed. Different body fluids and tissues samples were collected during postmortem examination. No relevant histopathological findings were observed. High levels of atrazine and its metabolites were detected in different fluids and tissues by ultra-liquid chromatography high performance coupled to triple quadrupole mass spectrometry. These findings suggest ruminal or hepatic metabolization of atrazine in the exposed cattle. This is the first report of quantification and distribution of atrazine and its metabolites in intoxicated mammals providing relevant information for diagnostic purposes.

Lack of correlation between central venous minus arterial PCO2 to arterial minus central venous O2 content ratio and respiratory quotient in patients with septic shock: A prospective observational study.

OBJECTIVE: Central venous-arterial PCO2 to arterial-central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation. Although Pcv-aCO2/Ca-cvO2 might be associated with hyperlactatemia and outcome, neither the interchangeability with RQ nor the correlation with conclusive variables of anaerobic metabolism has never been demonstrated in septic shock. Our goal was to compare Pcv-aCO2/Ca-cvO2 and RQ in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Two adult ICUs. PATIENTS: Forty-seven patients with septic shock on mechanical ventilation with stable respiratory settings and vasopressor dose after initial resuscitation. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We measured arterial and central venous gases, Hb, and O2Hb. Pcv-aCO2/Ca-cvO2 and the ratio of central venous-arterial CO2 content to arterial-central venous O2 content (Ccv-aCO2/Ca-cvO2) were calculated. RQ was determined by indirect calorimetry. RESULTS: Pcv-aCO2/Ca-cvO2 and Ccv-aCO2/Ca-cvO2 were not correlated with RQ (R2 = 0.01, P = 0.50 and R2 = 0.01, P = 0.58, respectively), showing large bias and wide 95 % limits of agreement with RQ (1.09, -1.10-3.27 and 0.42, -1.53-2.37). A multiple linear regression model showed Hb, and central venous PCO2 and O2Hb, but not RQ, as Pcv-aCO2/Ca-cvO2 determinants (R2 = 0.36, P = 0.0007). CONCLUSIONS: In patients with septic shock, Pcv-aCO2/Ca-cvO2 did not correlate with RQ and was mainly determined by factors that modify the dissociation of CO2 from Hb. Pcv-aCO2/Ca-cvO2 seems to be a poor surrogate for RQ; therefore, its values should be interpreted with caution.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Preparation and antitrypanosomal activity of secochiliolide acid derivatives.

Secochiliolide acid (1) isolated from the Patagonian shrub Nardophyllum bryoides, was used as a scaffold for the preparation of a series of nine derivatives. Compound 1 and its derivatives were tested against Trypanosoma cruzi epimastigotes grown in liquid media. It was first observed that secochiliolide acid (1) inhibited the proliferation of the parasites, with an IC50 of 2 µg/mL. Six of the synthesized derivatives were also active with IC50's between 2 and 7 µg/mL which are comparable to that of the commercial drug benznidazole (2.5 µg/mL). These results indicate that the carboxyl group is not essential for the bioactivity of 1, while the presence of the tetrasubstituted exocyclic double bond seems to be important. Moreover, the presence of the furan and spirolactone rings is not essential for the bioactivity per se, but is important in combination with other structural fragments present in the molecule.

Identification of Lactobacillus strains with probiotic features from the bottlenose dolphin (Tursiops truncatus).

AIMS: In order to develop complementary health management strategies for marine mammals, we used culture-based and culture-independent approaches to identify gastrointestinal lactobacilli of the common bottlenose dolphin, Tursiops truncatus. METHODS AND RESULTS: We screened 307 bacterial isolates from oral and rectal swabs, milk and gastric fluid, collected from 38 dolphins in the U.S. Navy Marine Mammal Program, for potentially beneficial features. We focused our search on lactobacilli and evaluated their ability to modulate TNF secretion by host cells and inhibit growth of pathogens. We recovered Lactobacillus salivarius strains which secreted factors that stimulated TNF production by human monocytoid cells. These Lact. salivarius isolates inhibited growth of selected marine mammal and human bacterial pathogens. In addition, we identified a novel Lactobacillus species by culture and direct sequencing with 96·3% 16S rDNA sequence similarity to Lactobacillus ceti. CONCLUSIONS: Dolphin-derived Lact. salivarius isolates possess features making them candidate probiotics for clinical studies in marine mammals. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to isolate lactobacilli from dolphins, including a novel Lactobacillus species and a new strain of Lact. salivarius, with potential for veterinary probiotic applications. The isolation and identification of novel Lactobacillus spp. and other indigenous microbes from bottlenose dolphins will enable the study of the biology of symbiotic members of the dolphin microbiota and facilitate the understanding of the microbiomes of these unique animals.

Scalable Query Answering Under Uncertainty to Neuroscientific Ontological Knowledge: The NeuroLang Approach.

Researchers in neuroscience have a growing number of datasets available to study the brain, which is made possible by recent technological advances. Given the extent to which the brain has been studied, there is also available ontological knowledge encoding the current state of the art regarding its different areas, activation patterns, keywords associated with studies, etc. Furthermore, there is inherent uncertainty associated with brain scans arising from the mapping between voxels-3D pixels-and actual points in different individual brains. Unfortunately, there is currently no unifying framework for accessing such collections of rich heterogeneous data under uncertainty, making it necessary for researchers to rely on ad hoc tools. In particular, one major weakness of current tools that attempt to address this task is that only very limited propositional query languages have been developed. In this paper we present NeuroLang, a probabilistic language based on first-order logic with existential rules, probabilistic uncertainty, ontologies integration under the open world assumption, and built-in mechanisms to guarantee tractable query answering over very large datasets. NeuroLang's primary objective is to provide a unified framework to seamlessly integrate heterogeneous data, such as ontologies, and map fine-grained cognitive domains to brain regions through a set of formal criteria, promoting shareable and highly reproducible research. After presenting the language and its general query answering architecture, we discuss real-world use cases showing how NeuroLang can be applied to practical scenarios.

Fibroblast growth factor 23 and left ventricular hypertrophy in children on dialysis.

BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations associate with left ventricular hypertrophy (LVH) and adverse outcomes in adult patients with chronic kidney disease. We hypothesized that similar associations are present in pediatric patients on maintenance hemodialysis. METHODS: In this retrospective study of 26 young patients on chronic hemodialysis, aged 6-21 years, cardiac structure and geometry were measured by echocardiography, and circulating levels of FGF-23 and calciotropic hormones were obtained. RESULTS: FGF-23 levels were uniformly elevated in all patients from three- to 835-fold above the upper limit of normal. The average LV mass index (LVMI) was 43 ± 13 g/m(2.7) and reflected LVH in 55 % of patients. Log-transformed FGF-23 concentrations correlated with LVMI (p = 0.03) and were independently associated with the interventricular septal thickness Z-score (p < 0.001). Concentric LVH was associated with the highest FGF-23 concentrations and the highest LVMI measurements (p < 0.001). Each 1 standard deviation increase in log-transformed FGF-23 levels was associated with a 17 % increase in LVMI. CONCLUSIONS: FGF-23 levels are strongly associated with increased LVMI and with prevalent LVH in pediatric hemodialysis patients. Our cross-sectional findings provide observational evidence supporting the hypothesis linking FGF-23 to cardiac hypertrophy in patients with chronic kidney disease.