Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images.

BACKGROUND AND OBJECTIVES: Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. RESULTS: We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. CONCLUSIONS: The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.

Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types.

Correction for 'Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types' by Todd McAlary et al., Environ. Sci.: Processes Impacts, 2015, 17, 896-905.

Passive sampling for volatile organic compounds in indoor air-controlled laboratory comparison of four sampler types.

This article describes laboratory testing of four passive diffusive samplers for assessing indoor air concentrations of volatile organic compounds (VOCs), including SKC Ultra II, Radiello®, Waterloo Membrane Sampler (WMS) and Automated Thermal Desorption (ATD) tubes with two different sorbents (Tenax TA and Carbopack B). The testing included 10 VOCs (including chlorinated ethenes, ethanes, and methanes, aromatic and aliphatic hydrocarbons), spanning a range of properties and including some compounds expected to pose challenges (naphthalene, methyl ethyl ketone). Tests were conducted at different temperatures (17 to 30 °C), relative humidities (30 to 90% RH), face velocities (0.014 to 0.41 m s(-1)), concentrations (1 to 100 parts per billion by volume [ppbv]) and sampling durations (1 to 7 days). The results show that all of the passive samplers provided data that met the success criteria (relative percent difference [RPD] ≤ 45% of active sample concentrations and coefficient of variation [COV] ≤ 30%) in the majority of cases, but some compounds were problematic for some samplers. The passive sampler uptake rates depend to varying degrees on the sampler, sorbent, target compounds and environmental conditions, so field calibration is advantageous for the highest levels of data quality.

Quantitative passive soil vapor sampling for VOCs--Part 4: Flow-through cell.

This paper presents a controlled experiment comparing several quantitative passive samplers for monitoring concentrations of volatile organic compound (VOC) vapors in soil gas using a flow-through cell. This application is simpler than conventional active sampling using adsorptive tubes because the flow rate does not need to be precisely measured and controlled, which is advantageous because the permeability of subsurface materials affects the flow rate and the permeability of geologic materials is highly variable. Using passive samplers in a flow-through cell, the flow rate may not need to be known exactly, as long as it is sufficient to purge the cell in a reasonable time and minimize any negative bias attributable to the starvation effect. An experiment was performed in a 500 mL flow-through cell using a two-factor, one-half fraction fractional factorial test design with flow rates of 80, 670 and 930 mL min(-1) and sample durations of 10, 15 and 20 minutes for each of five different passive samplers (passive Automatic Thermal Desorption Tube, Radiello®, SKC Ultra, Waterloo Membrane Sampler™ and 3M™ OVM 3500). A Summa canister was collected coincident with each passive sampler and analyzed by EPA Method TO-15 to provide a baseline for comparison of the passive sampler concentrations. The passive sampler concentrations were within a factor of 2 of the Summa canister concentrations in 32 of 35 cases. Passive samples collected at the low flow rate and short duration showed low concentrations, which is likely attributable to insufficient purging of the cell after sampler placement.

Validation of a radial diffusive sampler for measuring occupational exposure to 1,3-butadiene.

1,3-Butadiene (BD) is a major industrial chemical used in the manufacture of rubbers and latexes; it is also a ubiquitous environmental pollutant whose major source is traffic. Occupational exposure to (BD) can occur both during its production and during its use as a raw material. The objective of the study was the laboratory and field validation of a new diffusive sampler for BD. The nominal sampling rate of the Radiello diffusive sampler filled with Carbopack X is 30.5 cm(3)/min, at 0.177 mg/m(3), 20 °C and 50% relative humidity (RH), for an 8-h exposure time. A model can be used for calculating the sampling rate as a function of temperature, time and RH. The concentration does not affect the sampling rate above 30 µg/m(3). The measurement uncertainty (k=2), calculated both by laboratory data and by field comparison according to International Standard Organization (ISO) 13752, satisfies the EN 482:2006 requirement for measurements between 0.1 and 0.5 times the threshold limit value-time weighted average (TLV-TWA) (uncertainty<50%). For field validation study, 38 workers exposed to BD and 20 administrative employees, as the control group, underwent environmental and biological monitoring. Personal exposure to BD was measured by diffusive samplers (Radiello) in comparison with active samplers. The BD exposure levels detected for the exposed subjects were low (mean 0.059, range <0.010-1.340 mg/m(3)) but higher than the controls levels, all below 0.010 mg/m(3). The comparison between diffusive and active (pumped) air sampling showed a good correlation, with no systematic deviation from the ideal values of the intercept and slope of the optimized regression line. The concentrations of two biomarkers were also determined on urine samples, collected at the end of the work-shift: unchanged BD, by GC-MS, and the metabolite dihydroxybutylmercapturic acid (DHBMA), by HPLC-MS/MS. The urinary excretion of the biomarkers was on average higher in the exposed group (urinary BD: mean 8.8, range <1-48.1 ng/l; DHBMA: mean 0.232, range 0.016-0.572 mg/l) than in controls (urinary BD: mean 6.4, range 2.6-14.5 ng/l; DHBMA: mean 0.205, range 0.037-0.602 mg/l), but a statistically significant difference was achieved only for unchanged BD and not for DHBMA. In conclusion, the environmental monitoring measured by diffusive samplers (Radiello) appears to be a reliable method for the assessment of exposure to low levels of airborne BD and a convenient alternative to the conventional active sampling.

Quantitative passive soil vapor sampling for VOCs--part 2: laboratory experiments.

Controlled laboratory experiments were conducted to demonstrate the use of passive samplers for soil vapor concentration monitoring. Five different passive samplers were studied (Radiello, SKC Ultra, Waterloo Membrane Sampler, ATD tubes and 3M OVM 3500). Ten different volatile organic compounds were used of varying classes (chlorinated ethanes, ethanes, and methanes, aliphatics and aromatics) and physical properties (vapor pressure, solubility and sorption). Samplers were exposed in randomized triplicates to concentrations of 1, 10 and 100 ppmv, with a relative humidity of ∼80%, a temperature of ∼24 °C, and a duration of 30 minutes in a chamber with a face velocity of about 5 cm min(-1). Passive samplers are more commonly used for longer sample durations (e.g., 8 hour workday) and higher face velocities (>600 cm min(-1)), so testing to verify the performance for these conditions was needed. Summa canister samples were collected and analyzed by EPA Method TO-15 to establish a baseline for comparison for all the passive samplers. Low-uptake rate varieties of four of the samplers were also tested at 10 ppmv under two conditions; with 5 cm min(-1) face velocity and stagnant conditions to assess whether low or near-zero face velocities would result in a low bias from the starvation effect. The results indicate that passive samplers can provide concentration measurements with accuracy (mostly within a factor of 2) and precision (RSD < 15%) comparable to conventional Summa canister samples and EPA Method TO-15 analysis. Some compounds are challenging for some passive samplers because of uncertainties in the uptake rates, or challenges with retention or recovery.

Quantitative passive soil vapor sampling for VOCs--part 3: field experiments.

Volatile organic compounds (VOCs) are commonly associated with contaminated land and may pose a risk to human health via subsurface vapor intrusion to indoor air. Soil vapor sampling is commonly used to assess the nature and extent of VOC contamination, but can be complicated because of the wide range of geologic material permeability and moisture content conditions that might be encountered, the wide variety of available sampling and analysis methods, and several potential causes of bias and variability, including leaks of atmospheric air, adsorption-desorption interactions, inconsistent sampling protocols and varying levels of experience among sampling personnel. Passive sampling onto adsorbent materials has been available as an alternative to conventional whole-gas sample collection for decades, but relationships between the mass sorbed with time and the soil vapor concentration have not been quantitatively established and the relative merits of various commercially available passive samplers for soil vapor concentration measurement is unknown. This paper presents the results of field experiments using several different passive samplers under a wide range of conditions. The results show that properly designed and deployed quantitative passive soil vapor samplers can be used to measure soil vapor concentrations with accuracy and precision comparable to conventional active soil vapor sampling (relative concentrations within a factor of 2 and RSD comparable to active sampling) where the uptake rate is low enough to minimize starvation and the exposure duration is not excessive for weakly retained compounds.

Exposure to benzene and childhood leukaemia: a pilot case-control study.

OBJECTIVES: Main purpose To evaluate the feasibility of a measurement-based assessment of benzene exposure in case-control studies of paediatric cancer; Additional aims To identify the sources of exposure variability; to assess the performance of two benzene biomarkers; to verify the occurrence of participation bias; to check whether exposures to benzene and to 50 Hz magnetic fields were correlated, and might exert reciprocal confounding effects. DESIGN: Pilot case-control study of childhood leukaemia and exposure to benzene assessed by repeated seasonal weekly measurements in breathing zone air samples and outside the children's dwellings, with concurrent determinations of cotinine, t-t-muconic acid (MA) and sulfo-phenylmercapturic acid (S-PMA) in urine. PARTICIPANTS: 108 cases and 194 controls were eligible for inclusion. RESULTS: Full-participation was obtained from 46 cases and 60 controls, with low dropout rates before four repeats (11% and 17%); an additional 23 cases and 80 controls allowed the collection of outdoor air samples only. The average benzene concentration in personal and outdoor air samples was 3 µg/m(3) (SD 1.45) and 2.7 µg/m(3) (SD 1.41), respectively. Personal exposure was strongly influenced by outdoor benzene concentrations, higher in the cold seasons than in warm seasons, and not affected by gender, age, area of residence or caseness. Urinary excretion of S-PMA and personal benzene exposure were well correlated. Outdoor benzene levels were lower among participant controls compared with non-participants, but did not differ between participant and non-participant cases; the direction of the bias was found to depend on the cut-point chosen to distinguish exposed and unexposed. Exposures to benzene and extremely low-frequency magnetic fields were positively correlated. CONCLUSIONS: Repeated individual measurements are needed to account for the seasonal variability in benzene exposure, and they have the additional advantage of increasing the study power. Measurement-based assessment of benzene exposure in studies of childhood leukaemia appears feasible, although it is financially and logistically demanding.

[Role of inflammation on renal anaemia]. / Ruolo dell'infiammazione nell'anemia renale.

It is well-known the central role of inflammation in the inhibition of erythropoiesis and iron availability in chronic kidney disease (CKD) patients with erythropoietin (EPO)-resistant anaemia. This inflammatory action is mediated by suppressive cytokines (i.e. IL-6, TNF-, INF-) inhibiting differentiation and proliferation activities of erythroid cells in the EPO-indipendent phase of erythropoiesis and stimulating hepcidin production for iron retention in reticulo-endothelial system and enterocytes. EPO resistance is associated with adverse outcomes, such as cardiovascular disease, faster progression to end stage renal disease and mortality. Treatment of the causes of EPO hyporesponsiveness including chronic inflammation results in an improvement of anaemia and a reduction in EPO requirements.

Air pollution and increased levels of fractional exhaled nitric oxide in children with no history of airway damage.

Air pollution is associated with a wide range of adverse respiratory events. In order to study the mechanism associated with these effects, the relationships between fractional exhaled nitric oxide (FeNO), a potential marker of airway inflammation, and exposure to air pollution were examined in schoolchildren. FeNO was measured in 104 children (34 asthmatics and 70 non-asthmatics) drawn from the general population simultaneously with air pollution assessments (fine particles with an aerodiameter under 2.5 microm, nitrogen dioxide, acetaldehyde, and formaldehyde, with pumps and passive samplers) in schoolyards and classrooms. Asthmatics exhaled more FeNO than non-asthmatics. FeNO levels were significantly elevated in both asthmatic and non-asthmatic children exposed to high concentrations of formaldehyde, acetaldehyde, and PM(2.5). Differences between high versus low exposure in non-asthmatics resulted in an FeNO increase ranging from 45% for indoor acetaldehyde to 62% for indoor PM(2.5). Stronger associations were found in non-asthmatic children who were atopic, suggesting that atopic children may be more sensitive to air pollution than non-atopic children. Exposure to air pollution may lead to airway inflammation, as measured by FeNO, in schoolchildren. These associations occur even in children with no history of airway damage and seem to be enhanced in atopic subjects.

Maternal personal exposure to airborne benzene and intrauterine growth.

BACKGROUND: Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. OBJECTIVE: Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. METHODS: We recruited pregnant women in two French maternity hospitals in 2005-2006 as part of the EDEN mother-child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. RESULTS: Median benzene exposure was 1.8 microg/m(3) (5th, 95th percentiles, 0.5, 7.5 microg/m(3)). Log-transformed benzene exposure was associated with a gestational age-adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), -135 to -1 g] and of 1.9 mm in mean head circumference at birth (95% CI, -3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, -4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, -3.1 to 0 mm). CONCLUSIONS: Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.

Field evaluation of thermal and chemical desorption BTEX radial diffusive sampler radiello compared with active (pumped) samplers for ambient air measurements.

The performance of two types of radiello diffusive samplers, filled with a thermally desorbable adsorbent (graphitised carbon Carbograph 4) and with a solvent desorbable adsorbent (activated charcoal), respectively, have been evaluated for the monitoring of BTEX in ambient air, by comparison with active (pumped) samplers. A two year survey was carried out in Padua, a medium-sized town, in a traffic site, close to a busy crossroad. The concentrations of BTEX were measured for 15 campaigns, during which four series of radial diffusive samplers were exposed for 2 day, 7 day, 10 day and 14 day time periods, respectively. Every series of chemical desorption samplers included three replicates; thermal desorption samplers included six replicates, three of them filled with freshly conditioned cartridges and three filled with regenerated cartridges. No significant difference in the levels measured either by new or by regenerated cartridges has been found. During three campaigns (summer 2004, winter and spring 2005) two active (pumped) samplers were added for each sampling period. The diffusive uptake rates have been calculated and modelled under various conditions of concentration, temperature and exposure time. The effects of the environmental factors on the performances of both solvent and thermally desorbable samplers have been evaluated. The repeatability of the whole measurement process (sampling and analysis) was calculated for every sampling duration. The comparison of concentration levels measured by diffusive and active sampling methods shows correlation coefficients R >or= 0.98 (p<0.01) for all the compounds. The uncertainty of the diffusive sampling method under field conditions, using active sampling as the reference method, has been assessed according to the ISO 13752 requirements. On field relative expanded uncertainty for benzene has been found below 20%.

Analysis of indoor gaseous formic and acetic acid, using radial diffusive samplers.

A diffusive sampling method for the determination of gaseous acetic and formic acids, using a radial symmetry diffusive sampler, has been optimised for a 7-day exposure time in this study. Sampling rate determinations were performed on data obtained from a dynamic exposure chamber, simulating the indoor conditions of an empty, closed, room, at room temperature and minimal wind speed. Analysis has been performed by means of ion chromatography. The sampling rates for formic acid concentrations of 128 microg m(-3) and 1248 microg m(-3) were determined to be 91.2 +/- 3.9 ml min(-1) and 111.6 +/- 2.8 ml min(-1), respectively. The acetic acid sampling rate was independent of the concentration in the range 160 microg m(-3)-1564 microg m(-3), and amounted to 97.3 +/- 3.1 ml min(-1). Experimentally determined sampling rates showed deviations of 3% for acetic acid, and 3-21% for formic acid, in relation to theoretically derived values. The blank values were as low as 1.69 +/- 0.07 microg for formic acid and 1.21 +/- 0.14 microg for acetic acid, and detection limits lower than 0.5 microg m(-3) could be achieved, which is an improvement of 98-99% compared to previously validated diffusive sampling methods. This study describes the first step of an extended validation program in which the applicability of these types of samplers for the measurement of organic acids will be validated and optimised for the environmental conditions typical for museum showcases.

Evaluation of the best compromise between the urban air quality monitoring resolution by diffusive sampling and resource requirements.

The need to collect data representative of overall urban pollution is all-important in order to monitor the population exposure. High spatial resolution monitoring using diffusive samplers allows studying of the urban pollutant distribution, thus enabling deeper investigation of their generation and diffusion mechanisms. Nevertheless, such a monitoring campaign has a certain cost. In this study we point out how to find the best compromise between the number of necessary measurements and the affordable costs for monitoring campaigns. We also describe an innovative method for the proper design of a fixed urban monitoring network by means of preliminary high spatial resolution campaigns using diffusive samplers. Four European capital cities (Dublin, Madrid, Paris and Rome) were monitored six times, each time for seven days. Benzene, toluene, ethylbenzene, xylenes (BTEX) and NO(2) concentrations were measured at 146 sites in Dublin, 293 in Madrid, 339 in Paris and 290 in Rome. Multiscale grids have been drawn which ranged in mesh size from 500 m to 2 km. The statistical processing of data produced a twofold result: the creation of isoconcentration maps with geostatistical procedures, and an algorithm aimed at locating the minimum number of sampling sites where the fixed monitoring stations should be placed. Average urban levels estimated on the basis of these selected sites differ by less than 8% from those calculated on the whole populations of the sampled points. The aim of this work is to investigate how far the resolution of a monitoring campaign of urban pollution by diffusive sampling can be reduced, thus making the monitoring less expensive in terms of human and financial resources, while preserving the same quality of the results that could be achieved with a higher resolution. We found that there is no significant loss of information when the resolution of the monitoring grid for BTEX is lowered to a mesh size of 1.85 km, that is a sampling site each 3.4 km(2), and that the minimum number of sampling sites to be used is N = 0.29 A, where A is the urban surface to be monitored (in km(2)). As the spatial distribution of NO(2) is less sensitive to the distance from the emission source than that of BTEX, this relationship could be retained as a valid lower limit for the mesh grid size also for NO(2) monitoring.

Long-term intravenous epoetin-alpha / darbepoetin-alpha ratio in iron-replete hemodialysis patients.

BACKGROUND: Equivalence of intravenous (i.v.) and subcutaneous (s.c.) dosage requirements is a notable characteristic of darbepoetin-alpha (DPO), as opposed to other epoetins (EPOs). Currently in Europe, the EPOs/DPO conversion factor (200 IU EPOs = 1 microg DPO) does not take into account the route of drugs administration. To better define this ratio we have conducted a prospective, long-term trial in a group of hemodialysis patients. SUBJECTS AND METHODS: At the start, we evaluated 40 iron-replete hemodialysis patients, but the final study was performed in the remaining 25 patients. During the first 6 months, patients were on i.v. epoetin-alpha (EPOalpha) maintenance therapy (phase 1: T-6 to T0). After conversion to i.v. DPO (initial 200:1 ratio) the observation was prolonged for a period of 12 months (phase 2: T0 to T12). DPO was administered at extended dose intervals and the EPOalpha/DPO rate was adjusted every month to maintain hemoglobin (Hgb) stability. Iron status and factors inhibiting erythropoiesis were continually checked to exclude unstable patients. RESULTS: Phase 1: EPOalpha weekly mean dose showed no significant variation. Phase 2: EPOalpha/DPO conversion factor progressively rose from 200 to 256.7 +/- 86.9 IU/microg at T7 (p<0.005) and 336.8 +/- 104.3 IU/microg at T12 (p<0.0005). DPO weekly mean dosage decreased from 40.0 +/- 12.0 microg/week at T0 to 31.6 +/- 3.7 microg/week at T7 (p<0.005) and 24.6 +/- 7.0 microg/week at T12 (p<0.0005). Mean weekly/patient acquisition cost of EPOalpha was euro 70.6 +/- 21.3 (T-6 to T0); after switching, the cost of DPO was euro 72.4 +/- 22.7 (T0) and fell to euro 53.1 +/- 11.2 during T6 to T12. CONCLUSIONS: The progressive increase of EPOalpha/DPO ratio demonstrated that i.v. DPO requires lower doses compared with i.v. EPOalpha. When drugs are administered i.v., the starting EPOalpha/DPO conversion factor should be increased over the 200:1 ratio, similar to recommendations outlined in the United States and Japan. DPO dose reduction translated to notable cost-savings.

Acute effects of peritoneal dialysis with dialysates containing dextrose or dextrose and amino acids on muscle protein turnover in patients with chronic renal failure.

Whether changes in substrate and insulin levels that occur during peritoneal dialysis (PD) have effects on muscle protein dynamics was evaluated by studying muscle protein synthesis (PS), breakdown (PB), and net protein balance (NB) by the forearm perfusion method associated with the kinetics of 3H-phenylalanine in acute, crossover studies in which PD patients served as their own controls. Studies were performed (1) in the basal state and during PD with dialysates that contained dextrose alone in different concentrations (protocol 1: eight patients), (2) during PD with dialysates that contained dextrose alone or dextrose and amino acids (AA) (protocol 2: five patients), and (3) in time controls (five patients). PD with dextrose alone induced (1) a two- to threefold increase in insulin, as well as a 20 to 25% decrease in AA, mainly BCAA, levels; (2) an insulin-related decline (-18%) in forearm PB (P<0.002); (3) a 20% decrease in muscle PS (P<0.04), which was related to arterial BCAA and K+ (P<0.02 to 0.05); (4) a persistent negative NB; and (5) a decrease in the efficiency of muscle protein turnover, expressed as the ratio NB/PB. PD with dextrose+AA versus PD with dextrose induced (1) similarly high insulin levels but with a significant increase in total arterial AA (+30 to 110%), mainly valine; (2) a reduced release of AA from muscle (P<0.05); and (3) a decrease in the negative NB observed during PD with dextrose, owing to an increase (approximately 20%) in muscle PS, without any further effect on muscle PB. This study indicates that in PD patients in the fasting state, the moderate hyperinsulinemia that occurs during PD with dextrose alone causes an antiproteolytic action that is obscured by a parallel decrease in AA availability for PS. Conversely, the combined use of dextrose and AA results in a cumulative effect, because of the suppression of endogenous muscle PB (induced by insulin) and the stimulation of muscle PS (induced by AA availability). The hypothesis, therefore, is that in patients who are treated with PD, when fasting or when nutrient intake is reduced, muscle mass could be maintained better by the combined use of dextrose and AA.

Effects of growth hormone on leptin metabolism and energy expenditure in hemodialysis patients with protein-calorie malnutrition.

The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 +/- 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P: < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P: < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P: < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P: < 0.02). Similarly, variations in leptin levels were directly related to insulin (P: < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P: < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.