Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Medullary Blood Oxygen Level-Dependent MRI Index (R2*) is Associated with Annual Loss of Kidney Function in Moderate CKD.

BACKGROUND: The estimated glomerular filtration rate (eGFR) is frequently used to monitor progression of kidney disease. Multiple values have to be obtained, sometimes over years to determine the rate of decline in kidney function. Recent data suggest that functional MRI (fMRI) methods may be able to predict loss of eGFR. In a prior study, baseline data with multi-parametric MRI in individuals with diabetes and moderate CKD was reported. This report extends our prior observations in order to evaluate the temporal variability of the fMRI measurements over 36 months and their association with annual change in eGFR. METHODS: Twenty-four subjects with moderate CKD completed 3 sets of MRI scans over a 36-month period. Blood oxygenation level-dependent (BOLD), arterial spin labeling perfusion, and diffusion MRI images were acquired using a 3 T scanner. Coefficients of variation was used to evaluate variability between subjects at each time point and temporal variability within each subject. We have conducted mixed effects models to examine the trajectory change in GFR over time using time and MRI variables as fixed effects and baseline intercept as random effect. Associations of MRI image markers with annual change in eGFR were evaluated. RESULTS: Multi-parametric functional renal MRI techniques in individuals with moderate CKD showed higher temporal variability in R2* of medulla compared to healthy individuals. This was consistent with the significant lower R2* in medulla observed at 36 months compared to baseline values. The results of linear mixed model showing that R2*_Medulla was the only predictor associated with change in eGFR over time. Furthermore, a significant association of medullary R2* with annual loss of eGFR was observed at all the 3 time points. CONCLUSIONS: The lower R2* values and the higher temporal variability in the renal medulla over time suggest the ability to monitor progressive CKD. These were confirmed by the fact that reduced medullary R2* was associated with higher annual loss in eGFR. These data collectively emphasize the need for inclusion of medulla in the analysis of renal BOLD MRI studies.

Renal BOLD MRI in patients with chronic kidney disease: comparison of the semi-automated twelve layer concentric objects (TLCO) and manual ROI methods.

OBJECTIVE: Blood oxygenation level dependent (BOLD) MRI technique is used to evaluate changes in intra-renal oxygenation in chronic kidney disease (CKD). The purpose of this study was to evaluate if the novel twelve layer concentric objects (TLCO) method has advantages over the manually defined regions of interest (ROI) analysis. METHODS AND MATERIALS: Existing renal BOLD MRI data acquired before and after furosemide on a 3 T scanner from 41 CKD patients and 13 age matched healthy controls were analyzed using TLCO method and compared with previously reported ROI analysis. RESULTS: Regional R2* measurements were strongly correlated between the two methods, while ΔR2* was moderately correlated. Medullary R2* by ROI analysis showed higher values compared to R2*_Inner by TLCO, probably due to the contributions from the cortex to R2*_Inner. R2*_Slope and Δ(R2*_Slope), unique parameters based on the TLCO method provided the most significant differences between stage 3a CKD patients and controls and were correlated with eGFR. DISCUSSION: There was a high degree of agreement between the two methods in terms of regional R2* measurements and both methods did not show differences between moderate CKD patients and controls. However, R2*_Slope and Δ(R2*_Slope) showed the largest sensitivity in distinguishing CKD from controls.

Cortical Perfusion and Tubular Function as Evaluated by Magnetic Resonance Imaging Correlates with Annual Loss in Renal Function in Moderate Chronic Kidney Disease.

BACKGROUND: Chronic hypoxia is a well-recognized factor in the pathogenesis of chronic kidney disease (CKD). Loss of microcirculation is thought to lead to enhanced renal hypoxia, which in turn results in the development of fibrosis, a hallmark of progressive CKD. To evaluate the role of functional magnetic resonance imaging (MRI), we performed perfusion, oxygenation, and diffusion MRI measurements in individuals with diabetes and stage 3 CKD. METHODS: Fifty-four subjects (41 individuals with diabetes and stage 3 CKD and 13 healthy controls) participated in this study. Data with blood oxygenation level dependent (BOLD), arterial spin labeling perfusion and diffusion MRI were acquired using a 3T scanner. RESULTS: Renal cortical perfusion was reduced in CKD compared to the controls (109.54 ± 25.38 vs. 203.17 ± 27.47 mL/min/100 g; p < 0.001). Cortical apparent diffusion coefficient showed no significant reduction in CKD compared to controls (1,596.10 ± 196.64 vs. 1,668.72 ± 77.29 × 10-6 mm2/s; p = 0.45) but was significantly associated with perfusion. Cortical R2* values were modestly increased in CKD (20.76 ± 4.08 vs. 18.74 ± 2.37 s-1; p = 0.12). Within the CKD group, R2*_Medulla and R2*_Kidney were moderately and negatively associated with estimated glomerular filtration rate. There was a significant association between cortical perfusion and medullary response to furosemide with annual loss of renal function, used as an estimate of CKD progression. CONCLUSIONS: Subjects with a moderate degree of CKD had significantly lower renal perfusion. Diffusion and BOLD MRI showed more modest differences between the groups. Individuals with progressive CKD had lower perfusion and response to furosemide.

Consistency of Multiple Renal Functional MRI Measurements Over 18 Months.

BACKGROUND: Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies. PURPOSE/HYPOTHESIS: To investigate the consistency of repeated functional MRI measurements in healthy subjects. STUDY TYPE: Prospective, longitudinal study. SUBJECTS: Seventeen healthy subjects were examined on two different occasions, 18 months apart. FIELD STRENGTH/SEQUENCE: Multiple gradient-recalled-echo, 2D navigator-gated flow-sensitive alternating inversion recovery True-FISP and spin-echo planar diffusion-weighted sequences were used on a 3T scanner. Images were acquired on two different scanner configurations. ASSESSMENT: Blood oxygenation level-dependent (BOLD) R2*, arterial spin labeling (ASL) perfusion-derived blood flow (BF) and apparent diffusion coefficient (ADC) maps were analyzed using a custom image processing toolbox. Regions of interest (ROIs) were placed on renal cortex, medulla, and whole kidney. Multiple researchers were involved in defining the ROIs. STATISTICAL TESTS: Intra- and intersubject coefficients of variation (CV) and Bland-Altman plots were used to measure consistency and evaluate bias in the measurements. A nonparametric Wilcoxon test was used to compare differences between two timepoints. RESULTS: The intrasubject CV for R2* and ADC were 6.8% and 5.3% with small (-3.8 and 5.3%) bias, respectively, comparing baseline and 18-month data. Intrasubject CV for renal cortex BF was higher (18.7%) compared to R2* and ADC, but comparable to prior literature values over shorter durations. It also exhibited a larger bias (-15.4%) between two timepoints and significantly lower values (P = 0.022) at 18-month data. DATA CONCLUSION: All three MRI parameters over 18 months, even with a scanner upgrade and involving multiple observers, showed good consistency. These results are useful for the interpretation of longitudinal data and support the use of these methods to monitor progression in patients with CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:514-521.

Quantitative Blood Oxygenation Level Dependent Magnetic Resonance Imaging for Estimating Intra-renal Oxygen Availability Demonstrates Kidneys Are Hypoxemic in Human CKD.

Introduction: Kidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in evaluating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2∗ is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2∗ and renal function decline have been described, it remains uncertain to what extent R2∗ is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue. Methods: This case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured. Results: This pilot study independently measured fBV in kidney cortex (0.23 ± 0.03 vs. 0.17 ± 0.03) and medulla (0.36 ± 0.08 vs. 0.25 ± 0.03) in a small number of healthy controls (n = 7) versus CKD (n = 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 ± 0.03 vs. 0.72 ± 0.10 in cortex; 0.82 ± 0.05 vs. 0.72 ± 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 ± 6.5 vs. 38.4 ± 7.6 mm Hg in cortex; 48.4 ± 6.2 vs. 38.1 ± 4.5 mm Hg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2∗ was not. Conclusion: Our results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

PURPOSE: To compare the effects of osmolality versus viscosity of radio-contrast media on intra-renal oxygenation as determined by blood oxygenation level-dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN). MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into five groups. Nitric oxide synthase inhibitor L-NAME (10 mg/kg), cyclooxygenase inhibitor indomethacin (10 mg/kg), or saline, and radio-contrast iodixanol (high viscosity, 784 or 1600 mg I/kg) or iothalamate (high osmolality, 1600 mg I/kg) were administered. BOLD MRI images were acquired on Siemens 3 Tesla (T) scanner using a multiple gradient recalled echo sequence at baseline, following L-NAME (or saline), indomethacin (or saline), and radio-contrast agents. R2* (=1/T2*) was used as the BOLD MRI parameter in renal medulla and cortex. Mixed-effects models with first order auto-regressive variance-covariance models were used to analyze the data. RESULTS: The magnitude of change in medullary R2* (MR2*) with same dose of iodine was larger with iodixanol compared with iothalalmate both in pretreated groups (303% versus 225.6%, < 0.01) and the control group (191.6% versus -1.8%, P < 0.01). The MR2* change in high dose iodixanol was approximately twice compared with the low dose (303% versus 133%, P < 0.01). CONCLUSION: The viscosity of radio-contrast seems to play a more significant role than osmolality in terms of renal oxygenation changes as evaluated by BOLD MRI. Additionally, iodixanol induced a dose-dependent increase in renal medullary hypoxia.

Radiomics-Based Image Phenotyping of Kidney Apparent Diffusion Coefficient Maps: Preliminary Feasibility & Efficacy.

Given the central role of interstitial fibrosis in disease progression in chronic kidney disease (CKD), a role for diffusion-weighted MRI has been pursued. We evaluated the feasibility and preliminary efficacy of using radiomic features to phenotype apparent diffusion coefficient (ADC) maps and hence to the clinical classification(s) of the participants. The study involved 40 individuals (10 healthy and 30 with CKD (eGFR < 60 mL/min/1.73 m2)). Machine learning methods, such as hierarchical clustering and logistic regression, were used. Clustering resulted in the identification of two clusters, one including all individuals with CKD (n = 17), while the second one included all the healthy volunteers (n = 10) and the remaining individuals with CKD (n = 13), resulting in 100% specificity. Logistic regression identified five radiomic features to classify participants as with CKD vs. healthy volunteers, with a sensitivity and specificity of 93% and 70%, respectively, and an AUC of 0.95. Similarly, four radiomic features were able to classify participants as rapid vs. non-rapid CKD progressors among the 30 individuals with CKD, with a sensitivity and specificity of 71% and 43%, respectively, and an AUC of 0.75. These promising preliminary data should support future studies with larger numbers of participants with varied disease severity and etiologies to improve performance.

The action of enhancing weak light capture via phototropic growth and chloroplast movement in plants.

To cope with fluctuating light conditions, terrestrial plants have evolved precise regulation mechanisms to help optimize light capture and increase photosynthetic efficiency. Upon blue light-triggered autophosphorylation, activated phototropin (PHOT1 and PHOT2) photoreceptors function solely or redundantly to regulate diverse responses, including phototropism, chloroplast movement, stomatal opening, and leaf positioning and flattening in plants. These responses enhance light capture under low-light conditions and avoid photodamage under high-light conditions. NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) and ROOT PHOTOTROPISM 2 (RPT2) are signal transducers that function in the PHOT1- and PHOT2-mediated response. NPH3 is required for phototropism, leaf expansion and positioning. RPT2 regulates chloroplast accumulation as well as NPH3-mediated responses. NRL PROTEIN FOR CHLOROPLAST MOVEMENT 1 (NCH1) was recently identified as a PHOT1-interacting protein that functions redundantly with RPT2 to mediate chloroplast accumulation. The PHYTOCHROME KINASE SUBSTRATE (PKS) proteins (PKS1, PKS2, and PKS4) interact with PHOT1 and NPH3 and mediate hypocotyl phototropic bending. This review summarizes advances in phototropic growth and chloroplast movement induced by light. We also focus on how crosstalk in signaling between phototropism and chloroplast movement enhances weak light capture, providing a basis for future studies aiming to delineate the mechanism of light-trapping plants to improve light-use efficiency.

Sensitivity of USPIO-enhanced R2 imaging to dynamic blood volume changes in the rat kidney.

PURPOSE: To determine whether MRI in combination with an intravascular contrast agent is sensitive to pharmacologically induced vasodilation and vasoconstriction in the rat kidney. MATERIALS AND METHODS: R(2) imaging was performed in 25 Sprague Dawley rats at 3 Tesla in the presence of ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) agent with a long plasma half-life. R(2) changes were measured following manipulation of blood volume by intravenous administration of adenosine, a short-acting vasodilator, or N(G)-nitro-L-arginine methyl ester (L-NAME), a long-acting nitric oxide synthase inhibitor with known vasoconstrictive effects. As a control, R(2) responses to adenosine and L-NAME were also examined in the absence of ferumoxytol. RESULTS: In the presence of ferumoxytol, adenosine induced a significant increase in R(2), while L-NAME produced a reduction, although the latter was not statistically significant. Control experiments revealed small R(2) changes in the absence of ferumoxytol. An incidental finding was that the cross-sectional area of the kidney also varied dynamically with adenosine and L-NAME. CONCLUSION: Our results suggest that ferumoxytol-enhanced R(2) imaging is sensitive to adenosine-induced vasodilation. The responses to L-NAME, however, were not statistically significant. The variations in kidney size and the R(2) changes in the absence of ferumoxytol may reflect alterations in the volume of the renal tubules.

MRI Mapping of the Blood Oxygenation Sensitive Parameter T2* in the Kidney: Basic Concept.

The role of hypoxia in renal disease and injury has long been suggested but much work still remains, especially as it relates to human translation. Invasive pO2 probes are feasible in animal models but not for human use. In addition, they only provide localized measurements. Histological methods can identify hypoxic tissue and provide a spatial distribution, but are invasive and allow only one-time point. Blood oxygenation level dependent (BOLD) MRI is a noninvasive method that can monitor relative oxygen availability across the kidney. It is based on the inherent differences in magnetic properties of oxygenated vs. deoxygenated hemoglobin. Presence of deoxyhemoglobin enhances the spin-spin relaxation rate measured using a gradient echo sequence, known as R2* (= 1/T2*). While the key interest of BOLD MRI is in the application to humans, use in preclinical models is necessary primarily to validate the measurement against invasive methods, to better understand physiology and pathophysiology, and to evaluate novel interventions. Application of MRI acquisitions in preclinical settings involves several challenges both in terms of logistics and data acquisition. This section will introduce the concept of BOLD MRI and provide some illustrative applications. The following sections will discuss the technical issues associated with data acquisition and analysis.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Intra-renal oxygenation in rat kidneys during water loading: effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation.

PURPOSE: To evaluate intra-renal oxygenation by blood oxygenation level dependent (BOLD) MRI in rat kidneys during water loading and to investigate if the NO donating moiety in naproxcinod could compensate for the effect of cyclooxygenase (COX) inhibition of naproxen. MATERIALS AND METHODS: Nineteen male Sprague Dawley rats were divided into three groups and dosed with vehicle, naproxen or naproxcinod by gavage for two weeks. On the day of the experiment, hypotonic saline with glucose was infused intravenously to induce water diuresis. BOLD MRI data to monitor renal oxygenation and timed urine samples for estimation of prostaglandins (PGs) and urine flow were obtained. RESULTS: The data in this study is consistent with previous experience in humans in that pre-treatment with naproxen abolished the improvement in medullary oxygenation during water loading. In addition, the inhibition of PGs by naproxcinod reached similar levels as naproxen but maintained the improvement in oxygenation in renal medulla during water loading. CONCLUSION: This suggests that naproxcinod may have less nephrotoxicity and that the NO donating moiety partially compensates for the hemodynamic effects of prostaglandin inhibition by naproxen.

Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes.

The objective of this study was to compare the ratio of renal oxygen availability (RO2) to glomerular filtration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%). The RO2:GFR (ms/mL/min) was calculated as RO2 (T2*, ms) divided by GFR (mL/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR was associated with higher UACR (r = -0.31, P = 0.03), RPF (r = -0.52, P = 0.0009), and fat mass (r = -0.33, P = 0.02). Lower medullary RO2:GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.

Epidemiological and clinical characteristics of fifty-six cases of COVID-19 in Liaoning Province, China.

BACKGROUND: Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of ß-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM: To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS: The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS: The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION: SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

Seoul virus and hantavirus disease, Shenyang, People's Republic of China.

An outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred among students in Shenyang Pharmaceutical University in 2006. We conducted a study to characterize etiologic agents of the outbreaks and clarify the origin of hantaviruses causing infections in humans and laboratory animals. Immunoglobulin (Ig) M or IgG antibodies against Seoul virus (SEOV) were detected in the serum samples of all 8 patients. IgG antibodies against hantavirus were also identified in laboratory rats, which were used by these students for their scientific research. Phylogenetic analysis showed that partial small segment sequences recovered from humans, laboratory rats, and local wild rats belonged to SEOV. Hantavirus sequences recovered from humans and laboratory rats clustered within 1 of 3 lineages of SEOV circulating among local wild rats in Shenyang. These results suggest that the HFRS outbreak in Shenyang was caused by SEOV that was circulating among local wild rats and had also infected the laboratory rats.

Blood oxygen level-dependent MR imaging of the kidneys.

Oxygenation status plays a major role in renal physiology and pathophysiology, and thus has attracted considerable attention in recent years. While much of the early work and a significant amount of present work is based on invasive methods or ex vivo analysis, and is therefore restricted to animal models, blood oxygen level-dependent (BOLD) MR imaging has been shown to extend these findings to human beings. BOLD MR imaging is most useful in monitoring effects of physiologic or pharmacologic maneuvers. Several teams around the world have demonstrated reproducible data and have illustrated several useful applications. Studies supporting the use of renal BOLD MR imaging in characterizing disease with prognostic value have also been reported. This article provides an overview of current state-of-the art of renal BOLD MR imaging.

[Comparison of the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus].

OBJECTIVE: To study the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus (HEV). METHODS: Serum samples from 92 healthy subjects, 71 cases suspected of hepatitis E, 55 patients with confirmed diagnosis of acute hepatitis E, 50 individuals with rheumatoid factor (RF) positive and 54 persons with anti-HAV IgM positive were detected with three hepatitis E diagnostic kits. MP-IgM (MP, Singapore), Wantai-IgM and anti-HEV IgG (Wantai, China). HEV RNA was analyzed with RT-PCR in 52 of 71 cases suspected of hepatitis E. RESULTS: In healthy subjects,cases suspected of hepatitis E and confirmed acute hepatitis E, the concordance between the two anti-HEV IgM reagents was 73.39% (160/218) and the significant differences in the positive rates of two assays were not observed [46.79% (102/218) vs 44.04% (96/218), chi2 = 0.62, P > 0.05]. Of 71 patients suspected of hepatitis E, the sensitivity for diagnosing acute hepatitis E of Wantai-IgM and MP-IgM were 83.08% (54/65) and 78.46% (51/65) (chi2 = 0.16, P > 0.05), respectively. Among those suspected of hepatitis E with HEV RNA positive, the sensitivity of Wantai-IgM was obviously higher than that of MP-IgM [(97.14%, 34/35) vs (74.29%, 26/35), chi2 = 4.9, P < 0.05]. 48 of 55 patients (87.27%) with confirmed diagnosis of hepatitis E were Wantai-IgM positive while 37 (67.27%) was MP-IgM positive (chi2 = 4.0, P < 0.05). The specificity of Wantai-IgM was higher than MP-IgM [100.00% (202/202) vs 89. 11% (180/202), chi2 = 20.05, P < 0.005]. RF and anti-HAV IgM might cause MP-IgM false positive without interference on Wantai-IgM. CONCLUSION: Wantai-IgM should be a good ELISA kit for the diagnosis of acute hepatitis E.

Early changes with diabetes in renal medullary hemodynamics as evaluated by fiberoptic probes and BOLD magnetic resonance imaging.

OBJECTIVE: We sought to evaluate the influence of streptozotocin (STZ)-induced diabetes on renal outer medullary pO2 and blood flow by invasive microprobes and to demonstrate feasibility that blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) can monitor these changes. MATERIALS AND METHODS: A total of 60 Wistar-Furth rats were used. Diabetes was induced by STZ in 48. Animals were divided into OxyLite group (n=30) and BOLD MRI groups (n=30) each with a 5 subgroups of 6 animals: control and 2, 5, 14, and 28 days after induction of diabetes. Outer renal medullary oxygen tension and blood flow were measured by the combined OxyLite/OxyFlo probes. RESULTS: Both OxyLite and BOLD MRI showed a significant increase in the renal hypoxia levels after STZ at all time points. However, no changes were observed in the outer renal medullary oxygen tension and blood flow between diabetic and control groups. CONCLUSIONS: These preliminary results suggest that hypoxic changes can be detected as early as 2 days in rat kidneys with diabetes by BOLD MRI and that these early changes are not dependent on blood flow.

Evaluation of Renal Blood Flow in Chronic Kidney Disease Using Arterial Spin Labeling Perfusion Magnetic Resonance Imaging.

INTRODUCTION: Chronic kidney disease (CKD) is known to be associated with reduced renal blood flow. However, data to-date in humans is limited. METHODS: In this study, non-invasive arterial spin labeling (ASL) MRI data was acquired in 33 patients with diabetes and stage-3 CKD, and 30 healthy controls. RESULTS: A significantly lower renal blood flow both in cortex (108.4±36.4 vs. 207.3±41.8; p<0.001, d=2.52) and medulla (23.2±8.9 vs. 42.6±15.8; p<0.001, d=1.5) was observed. Both cortical (ρ=0.67, p<0.001) and medullary (ρ=0.62, p<0.001) blood flow were correlated with eGFR, and cortical blood flow was found to be confounded by age and BMI. However, in a subset of subjects that were matched for age and BMI (n=6), the differences between CKD and control subjects remained significant both in cortex (107.4±42.8 vs. 187.51±20.44; p=0.002) and medulla (15.43±8.43 vs. 39.18±11.13; p=0.002). A threshold value to separate healthy and CKD was estimated to be Cor_BF=142.9 and Med_BF=24.1. CONCLUSION: These results support the use of ASL in the evaluation of renal blood flow in patients with moderate level of CKD. Whether these measurements can identify subjects at risk of progressive CKD requires further longitudinal follow-up.