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Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Oxford classification including mesangial hypercellularity (M), endothelial hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescent (C) were recommended to predict the prognosis of IgAN.To explore whether multiparametric magnetic resonance imaging (MRI) can be applied to assess the renal function, Oxford classification, and risk of progression to end-stage kidney disease within 5 years of IgAN.Prospective.A total of 46 patients with pathologically confirmed IgAN and 20 healthy volunteers.A 3-T, blood oxygenation level-dependent (BOLD)-MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).Two radiologists measured the cortex and medulla T2*, apparent diffusion coefficient (ADC), true diffusion (Dt), pseudo-diffusion (Dp), perfusion fraction (fp). All participants were divided into three groups: group 1, healthy volunteers; group 2, patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 mIntraclass correlation coefficient, one-way analysis of variance, least-significant difference, Student's t-test, Pearson product-moment correlation, Spearman's rank correlation, and receiver operating characteristics (ROC) with the area under the curve (AUC). A P value0.05 was considered statistically significant.Except for cortical Dp, all other MRI parameters showed significant differences between group 1 and group 2. None of the MRI parameters showed a significant correlation with M, E, or C scores. Cortical T2*, Dt, fp, and medullary Dt and fp showed low-to-moderate significant correlations with S scores. Except for cortical and medullary Dp, all other MRI parameters were significantly correlated with T scores. Cortical Dt showed the largest AUC for differentiating group A from group B (AUC = 0.927) and T0 from T1/T2 (AUC = 0.963).Imaging by IVIM-DWI and BOLD-MRI could facilitate noninvasive assessment of the renal function, Oxford classification, and prognostic risk of IgAN patients.2.Stage 3.

Purpose To investigate the potential of histogram analysis based on diffusion kurtosis imaging (DKI) in evaluating renal function and fibrosis associated with chronic kidney disease (CKD). Materials and methods Thirty-six CKD patients were enrolled, and DKI was performed in all patients before the renal biopsy. The histogram parameters of diffusivity (D) and kurtosis (K) were obtained using FireVoxel. The histogram parameters between the stable [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2] and impaired (eGFR 2) eGFR group were compared. Besides, patients were classified into mild, moderate, and severe fibrosis group using a semi-quantitative standard. The correlations of histogram parameters with eGFR and fibrosis scores were investigated and the diagnostic performances of histogram parameters in assessing renal dysfunction and fibrosis were analyzed. The added value of combination of most significant parameter with 24 h urinary protein (24 h-UPRO) in evaluating fibrosis was also explored. Results Seven D histogram parameters in cortex (mean, median, 10th, 25th, 75th, 90th percentiles and entropy), two D histogram parameters in medulla (75th, 90th percentiles), seven K histogram parameters in cortex (mean, min, median, 10th, 25th, 75th, 90th percentiles) and three K histogram parameters in medulla (mean, median, 25th percentile) were significantly different between the two groups. The Dmean of cortex was the most relevant parameter to eGFR (r = 0.648, P K90th of cortex presented the strongest correlation with fibrosis scores (r = 0.575, P K90th in cortex with 24 h-UPRO gained statistically higher AUC value (AUC = 0.880, 95% CI 0.763–0.996). Conclusion Histogram analysis based on DKI is practicable for the noninvasive assessment of renal function and fibrosis in CKD patients.

Purpose This paper was intended to describe the characteristics of coronavirus disease 2019 (COVID-19) patients with known chronic kidney disease (CKD) history. Methods Clinical information of 20 COVID-19 pneumonia patients with CKD history diagnosed between January 20th and March 1st, 2020 were collected in Tongji Hospital, Wuhan. We listed the clinical baseline data, laboratory findings, chest computed tomography (CT) changes and processed a short period of follow-up of these 20 patients. Results Based on the estimated glomerular filtration rate (eGFR) on admission, 6 patients were classified as stage 2 of CKD, 5 were as 3a, 2 were as 3b, 3 were as 4 and 4 were as 5, respectively. COVID-19 patients with CKD history were elder and hypertension was the most common comorbidity. Cough and fever accounted for more than 80% of the infectious cases. Lymphopenia, increased d-dimer and elevated infectious indications such as hypersensitive C response protein (hsCRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also common among these patients. Ground-glass opacity (GGO) and consolidation were the major manifestations in CT scans. 4 patients died and 7 patients underwent acute kidney injury (AKI) during observation. Among 16 discharged patients, 12 were with stable renal function and 4 had deteriorating renal function compared with that of admission. Conclusion Compared to general population infected with SARS-CoV-2, COVID-19 patients with CKD history had a preference to develop to severity with higher fatality rate.

Objectives To investigate the diagnostic value of contrast‐enhanced computed tomography (CECT) histogram analysis in predicting the World Health Organization (WHO) grade of rectal neuroendocrine tumors (R‐NETs). Materials and Methods A total of 61 (35 G1, 12 G2, 10 G3, and 4 NECs) patients who underwent preoperative CECT and treated with surgery to be confirmed as R‐NETs were included in this study from January 2014 to May 2019. We depicted ROIs and measured the CECT texture parameters (mean, median, 10th, 25th, 75th, 90th percentiles, skewness, kurtosis, and entropy) from arterial phase (AP) and venous phase (VP) images by two radiologists. We calculated intraclass correlation coefficient (ICC) and compared the histogram parameters between low‐grade (G1) and higher grade (HG) (G2/G3/NECs) by applying appropriate statistical method. We obtained the optimal parameters to identify G1 from HG using receiver operating characteristic (ROC) curves. Results The capability of AP and VP histogram parameters for differentiating G1 from HG was similar in several histogram parameters (mean, median, 10th, 25th, 75th, and 90th percentiles) (all p, CECT histogram parameters, including arterial phase and venous phase, can be used as excellent indicators for predicting G1 and HG of rectal neuroendocrine tumors, and the size of the tumor is also an important independent predictor.

Purpose To investigate the utility of diffusion kurtosis imaging (DKI) MRI for evaluation of renal fibrosis in rats with unilateral ureteral obstruction (UUO). Methods Twenty-five rats had UUO, and ten rats were subjected to sham operation as control. DKI was performed on a 3.0 T MRI scanner on days 1, 3, 5, and 7 after ligation. All rats then underwent 18F-FDG dynamic PET to evaluate unilateral renal function, followed by histological analysis to examine α-smooth muscle actin (α-SMA) expression. DKI metrics were assessed among the time points and between two sides, and compared with maximum standardized uptake value (SUVmax), serum levels of creatinine and urea, and fibrosis marker α-SMA. Results Mean kurtosis (MK) on day 7, axial kurtosis (Ka) on days 3 and 7, mean diffusivity (MD) on days 1, 3, 5, and 7, and fractional anisotropy (FA) on days 3, 5, and 7 of cortex and medulla between the UUO and contralateral sides were significantly different (all p Conclusions DKI shows the potential for noninvasive assessment of renal fibrosis and unilateral renal function induced by UUO.

Objectives To explore the diagnostic performance of diffusion kurtosis imaging (DKI) in evaluating the clinical and pathological characteristics of patients with immunoglobulin A nephropathy (IgAN) compared with conventional DWI. Materials and methods A total of 28 IgAN patients and 14 healthy volunteers prospectively underwent MRI examinations including coronal T2WI, axial T1WI, T2WI, and DWI sequences from September 2020 to August 2021. We measured mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) by using MR Body Diffusion Toolbox v1.4.0 (Siemens Healthcare). Patients were divided into three groups according to their estimated glomerular filtration rate (eGFR) (Group1, healthy volunteers without kidney disease or other diseases that affect renal function; Group2, IgAN patients with eGFR > 60 mL/min/1.73 m2; Group3, IgAN patients with eGFR 2). One-way analysis of variance, Pearson or Spearman correlation, and receiver operating characteristic curves were applied in our statistical analysis. Results MKCortex and ADCCortex showed significant differences between the Group1 and Group2. MKCortex, MDCortex, ADCCortex, MKMedulla, and ADCMedulla showed significant differences between Group2 and Group3. MKCortex had the highest correlation with CKD stages (r = 0.749, p r = 0.656, p Cortex had the highest correlation with glomerular lesion score (r = − 0.475, p = 0.011). MKCortex had the highest AUC (AUC = 0.923) for differentiating Group1 from Group2, and MDCortex had the highest AUC (AUC = 0.924) for differentiating Group2 from Group3, followed by MKMedulla (AUC = 0.923). Conclusions DKI is a feasible and reliable technique that can assess the clinical and pathological characteristics of IgAN patients and can provide more valuable information than conventional DWI, especially MKCortex.

Background The purpose of this study is to compare the diagnostic value, imaging quality and apparent diffusion coefficient (ADC) value of reduced field-of-view diffusion-weight imaging (r-FOV DWI) and full field-of-view diffusion-weight imaging (f-FOV DWI) in patients with gallbladder carcinoma and other lesions of gallbladder. Methods Two hundred ninety-six patients with gallbladder diseases underwent both r-FOV DWI and f-FOV DWI on a 3.0 T MRI scanner. Two radiologists assessed subjective image quality parameters independently. The Wilcoxon signed-rank test was used to compare subjective qualitative image score. Objective quality values and the mean ADC values were analyzed by paired t-test. The correlation between pathological results and mean ADC value were estimated using Spearman rank correlation analysis. Results The CNR value (10.23 ± 2.92) and image quality score (13.84 ± 1.07) of r-FOV DWI were significantly higher than those of f-FOV DWI (5.24 ± 1.29 PP = 0.239, 0.974 and 0.226 respectively). For both DWI sequences, the mean ADC values were the highest in the group of cholecystitis and the lowest in the group of gallbladder carcinoma (2.49 ± 0.14 vs 1.49 ± 0.12; 2.50 ± 0.14 vs 1.50 ± 0.13, for f-FOV and r-FOV respectively), the differences among groups were statistically significant (Pr = − 0.892, P Conclusion Reduced Field-of-view Diffusion-weighted MRI is a good tool to diagnosis the gallbladder carcinoma, with better image quality and without affecting ADC values.

Artificial intelligence can potentially provide a substantial role in streamlining chest computed tomography (CT) diagnosis of COVID-19 patients. However, several critical hurdles have impeded the development of robust AI model, which include deficiency, isolation, and heterogeneity of CT data generated from diverse institutions. These bring about lack of generalization of AI model and therefore prevent it from applications in clinical practices. To overcome this, we proposed a federated learning-based Unified CT-COVID AI Diagnostic Initiative (UCADI, http://www.ai-ct-covid.team/), a decentralized architecture where the AI model is distributed to and executed at each host institution with the data sources or client ends for training and inferencing without sharing individual patient data. Specifically, we firstly developed an initial AI CT model based on data collected from three Tongji hospitals in Wuhan. After model evaluation, we found that the initial model can identify COVID from Tongji CT test data at near radiologist-level (97.5% sensitivity) but performed worse when it was tested on COVID cases from Wuhan Union Hospital (72% sensitivity), indicating a lack of model generalization. Next, we used the publicly available UCADI framework to build a federated model which integrated COVID CT cases from the Tongji hospitals and Wuhan Union hospital (WU) without transferring the WU data. The federated model not only performed similarly on Tongji test data but improved the detection sensitivity (98%) on WU test cases. The UCADI framework will allow participants worldwide to use and contribute to the model, to deliver a real-world, globally built and validated clinic CT-COVID AI tool. This effort directly supports the United Nations Sustainable Development Goals’ number 3, Good Health and Well-Being, and allows sharing and transferring of knowledge to fight this devastating disease around the world.

Background To evaluate the clinical characteristics and angiographic features of transcatheter angiographic embolization (TAE) in patients with active bleeding after percutaneous nephrolithotomy (PCNL).Methods Between October 2009 and April 2018, 45 patients who underwent TAE for hemorrhage control after PCNL were reviewed retrospectively. Patient clinical characteristics and angiographic features of TAE were analyzed.Results Of the 3148 patients, 45 (1.4%), including 35 men (77.78%) and 10 women (22.22%), were treated with TAE after PCNL. Ten patients (22.22%) had a history of kidney surgery. The interval from the bleeding episode to TAE was 3 days (range, 1–6 days). In addition, 27 (60.0%) and 18 patients (40.0%) experienced sudden onset of bleeding and delayed bleeding, respectively. Arterial laceration, arteriovenous fistula, and negative angiographic finding was found in 28 (62.2%), 7 (15.6%), and 10 patients (22.2%), respectively. Thirty-five patients (92.1%) achieved primary clinical success. The median corrected hemoglobin decrease from bleeding episode to TAE was 52 g/L (25.25, 71.00). The median corrected hemoglobin decrease rate from bleeding episode to TAE was 13.11 g/L d (5.60, 26.12). The hemoglobin decrease from bleeding episode to TAE was lesser in negative angiographic patients (28.50 (10.75,51.25) g/L VS 53.7 (35.0,73.13) g/L) than in positive angiographic patients (PConclusion TAE is a safe and effective treatment for patients with post-PCNL bleeding. TAE should be performed for post-PCNL bleeding in patients with hemoglobin decrease of >25 g/L or hemoglobin decrease rate of >5.5 g/L·d following conservative management.

To assess whether spatial labeling with multiple inversion pulses (SLEEK) sequence can be employed as a one-stop assessment method for evaluating renal function and displaying renal artery in hypertensive patients with suspected renal dysfunction.A total of 78 patients with suspected hypertensive renal damage were enrolled in this retrospective study. All patients underwent MRI examinations, and both SLEEK and DWI sequences were performed simultaneously. According to estimated glomerular filtration rate (eGFR), patients were divided into three groups (Group 1, eGFR 90; Group 2, eGFR = 60-90; Group 3, eGFR 60). Twenty-two of these patients also underwent CT angiography (CTA) examination. Comparison between CTA, DWI, and eGFR was performed to assess the value of SLEEK in evaluating renal function and displaying renal artery.The performance of SLEEK to display renal artery was highly consistent with the results of CTA (kappa = 0.713). The corticomedullary contrast ratio positively correlated with eGFR (p = 0.004, r = 0.322) and was significantly higher in SLEEK images than in DWI images in all three groups (p 0.001). There was no significant difference in corticomedullary contrast ratio in SLEEK images between Group 1 and Group 2 (p = 0.285). However, the minimal renal cortical thickness, which significantly correlated with eGFR (p 0.001, r = 0.866), was significantly different between Group 1 and Group 2 (p 0.001). ROC analysis showed good diagnostic performance when differentiating patients with eGFR 60 from those with eGFR 60.The SLEEK sequence could evaluate simultaneously renal function through corticomedullary differentiation and renal arteries, enabling one-stop assessment in hypertensive patients with suspected renal dysfunction.• Spatial labeling with multiple inversion pulses (SLEEK) improves renal corticomedullary differentiation in hypertensive patients with renal dysfunction compared with DWI. • SLEEK clearly displays renal artery in hypertensive patients with renal dysfunction. • SLEEK could be utilized as a one-stop assessment method for evaluating renal function and renal artery in hypertensive patients.

SummaryBackgroundTo date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality.MethodIn this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses.FindingsWe included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21th,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospitaladmission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ∼5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (∼1.5 times risk of those without comorbid chronic illnesses).InterpretationTo prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm.FundingNone.

Background: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China imposes a major challenge in deciding and managing surgical operation on

Background: It is essential to discriminate low-grade (G1), intermediate-grade (G2) and high-grade (G3) rectal neuroendocrine tumors (R-NETs) due to the treatment decisions and postoperative management are totally different. CT histogram analysis, which is a novel method to provide objectively quantified assessment of tumor, may be helpful for differentiating the grade of R-NETs. Methods: A total of 61 (35 G1, 12 G2 and 14 G3) patients who underwent preoperative contrast-enhanced CT and treated with surgery to be confirmed as R-NETs were included in this study from January 2014 and May 2019. We accurately depicted the region of interest (ROI) and measured the CT texture parameters (mean, median, 10th, 25th, 75th, 90th percentiles, skewness, kurtosis and entropy) from arterial phase image by two radiologists. We calculated and compared these parameters between low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors by applying appropriate statistical method. We obtained the optimal parameters to identify G1 and G2/G3 by using receiver operating characteristic (ROC) curves. Findings: Histogram analysis of CT arterial phase imaging demonstrated significant differences between G1 and G2 or G3 group in several histogram parameters (mean, median, 10th, 25th, 75th and 90th percentiles) (all P 0.05). Skewness, kurtosis and entropy showed no significant differences among three groups ( P =0.449, 0.285, 0.057, respectively). ROC analysis showed a good predictive performance between G1 and G2/G3 and the mean generated the highest area under the curve (AUC = 0.832), followed by the median (AUC = 0.827). Interpretation: CT histogram parameters, especially mean and median, can be used as excellent indicators for predicting the grade (G1 and G2/G3) of rectal neuroendocrine tumors. Funding Statement: This study has received funding by the National Natural Science Foundation of China (Grant No.81771801,81801695, 81701657 and 81873623). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The Institutional Review Board of our hospital (Medical Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology) approved this retrospective study and the requirement for patient informed consent was waived.

Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21st ,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding Statement: This study was supported by grants from the “1000-Talents Program for Young Scholars” of China (X. Chen) and the “100-Talents Program for Elite Engineers” of the CAS (H. Jia). X. Chen is a junior fellow of the CAS Center for Excellence in Brain Science and Intelligence Technology. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study has been approved by the Ethics Commissions of Wuhan Tongji Hospital (TJ-IRB20200216). Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.

BACKGROUND: The incidence of chronic kidney disease (CKD) is high, and is easy to develop into end-stage renal disease (ESRD), which requires kidney dialysis or kidney transplantation. Therefore, we want to explore the clinical value of magnetic resonance quantitative histogram analysis based on spatial labeling with multiple inversion pulses (SLEEK) in assessing renal function in the early stage. METHODS: One hundred and twenty-nine patients underwent abdominal MRI examination, including a coronal SLEEK sequence. The patients were divided into the control group [CG, 47 cases, estimated glomerular filtration rate (eGFR) >90], the mild renal function impairment (mRI) group (48 cases, eGFR =60–90), and the moderate to severe renal function impairment (m-sRI) group (34 cases, eGFR

OBJECTIVE To investigate the value of combined chemical exchange saturation transfer (CEST) and conventional magnetization transfer imaging (MT) in detecting metabolic and structural changes of renal fibrosis in rats with unilateral ureteral obstruction (UUO) at 3T MRI. MATERIALS AND METHODS Thirty-five Sprague-Dawley rats underwent UUO surgery (n = 25) or sham surgery (n = 10). The obstructed and contralateral kidneys were evaluated on days 1, 3, 5, and 7 after surgery. After CEST and MT examinations, 18F-labeled fluoro-2-deoxyglucose positron emission tomography was performed to quantify glucose metabolism. Fibrosis was measured by histology and western blots. Correlations were compared between asymmetrical magnetization transfer ratio at 1.2 ppm (MTRasym(1.2ppm)) derived from CEST and maximum standard uptake value (SUVmax) and between magnetization transfer ratio (MTR) derived from MT and alpha-smooth muscle actin (α-SMA). RESULTS On days 3 and 7, MTRasym(1.2ppm) and MTR of UUO renal cortex and medulla were significantly different from those of contralateral kidneys (p < 0.05). On day 7, MTRasym(1.2ppm) and MTR of UUO renal cortex and medulla were significantly different from those of sham-operated kidneys (p < 0.05). The MTRasym(1.2ppm) of UUO renal medulla was fairly negatively correlated with SUVmax (r = -0.350, p = 0.021), whereas MTR of UUO renal medulla was strongly negatively correlated with α-SMA (r = -0.744, p < 0.001). CONCLUSION CEST and MT could provide metabolic and structural information for comprehensive assessment of renal fibrosis in UUO rats in 3T MRI and may aid in clinical monitoring of renal fibrosis in patients with chronic kidney disease.

To investigate the utility of diffusion kurtosis imaging (DKI) MRI for evaluation of renal fibrosis in rats with unilateral ureteral obstruction (UUO).Twenty-five rats had UUO, and ten rats were subjected to sham operation as control. DKI was performed on a 3.0 T MRI scanner on days 1, 3, 5, and 7 after ligation. All rats then underwentMean kurtosis (MK) on day 7, axial kurtosis (Ka) on days 3 and 7, mean diffusivity (MD) on days 1, 3, 5, and 7, and fractional anisotropy (FA) on days 3, 5, and 7 of cortex and medulla between the UUO and contralateral sides were significantly different (all p 0.05). Over the course of UUO progression, there were significant changes in Ka, MD and FA of medulla (all p 0.05). FA of medulla was positively correlated with SUVDKI shows the potential for noninvasive assessment of renal fibrosis and unilateral renal function induced by UUO.

As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production. Mitochondrial membrane potential (Δψm) and quantification of ATP synthesis were measured to evaluate mitochondrial function. The protein expression of Nox4, Nox2, and p22 was also detected to explore the effect of oxalate and MitoTEMPO on NADPH oxidase. Our results revealed that pretreatment with MitoTEMPO significantly inhibited oxalate induced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release and decreased oxalate induced mtROS generation. Further, MitoTEMPO pretreatment restored disruption of Δψm and decreased ATP synthesis mediated by oxalate. In addition, MitoTEMPO altered the protein expression of Nox4 and p22 and decreased the protein expression of IL-6 and osteopontin (OPN) induced by oxalate. We concluded that MitoTEMPO may be a new candidate to protect against oxalate induced kidney injury as well as urolithiasis.

Purpose To clarify the outcome of flexible ureteroscopy (fURS) for management of renal calculi without preoperative stenting. Methods A total of 171 patients who received 176 fURS procedures for unilateral renal stones were reviewed. All procedures were divided into two groups depending on whether they received ureteral stenting preoperatively. Baseline characteristics of patients, stone burden, operation time, stone-free rates, and complications were compared between both groups. Results Successful primary access to the renal pelvis was achieved in 104 of 114 (91.2%) patients without preoperative stenting, while all procedures with preoperative stenting (n = 62) were successfully performed. A total of 156 procedures were included for further data analysis (56 procedures in stenting group and 100 in non-stenting group). No significant differences was found regardless of a preoperative stent placement in terms of stone-free rate (73.2% with stenting vs. 71.0% without, P = 0.854), operative time (70.4 ± 32.8 with stenting vs. 70.2 ± 32.1 without, P = 0.969). Conclusions fURS for management of renal stone without preoperative ureteral stenting are associated with well outcome in short term follow-up. Our study may help patients and doctors to decide if an optional stent is placed or not.

Cdc42-interacting protein-4 (CIP4) is an F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family member that regulates membrane deformation and endocytosis, playing a key role in extracellular matrix (ECM) deposition and invasion of cancer cells. These processes are analogous to those observed during the initial epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. The role of CIP4 in renal tubular EMT and renal tubulointerstitial fibrosis was investigated over the course of the current study, demonstrating that the expression of CIP4 increased in the tubular epithelia of 5/6-nephrectomized rats and TGF-β1 treated HK-2 cells. Endogenous CIP4 evidenced punctate localization throughout the cytosol, with elevated levels observed in the perinuclear region of HK-2 cells. Subsequent to TGF-β1 treatment, CIP4 expression increased, forming clusters at the cell periphery that gradually redistributed into the cytoplasm. Simultaneously, EMT induction in cells was confirmed by the prevalence of morphological changes, loss of E-cadherin, increase in α-SMA expression, and secretion of fibronectin. Overexpression of CIP4 promoted characteristics similar to those commonly observed in EMT, and small interfering RNA (siRNA) molecules capable of CIP4 knockdown were used to demonstrate reversed EMT. Cumulatively, results of the current study suggest that CIP4 promotes TGF-β1-induced EMT in tubular epithelial cells. Through this mechanism, CIP4 is capable of inducing ECM deposition and exacerbating progressive fibrosis in chronic renal failure.

Cdc42-interacting protein-4 (CIP4) is an F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family member that regulates membrane deformation and endocytosis, playing a key role in extracellular matrix (ECM) deposition and invasion of cancer cells. These processes are analogous to those observed during the initial epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. The role of CIP4 in renal tubular EMT and renal tubulointerstitial fibrosis was investigated over the course of the current study, demonstrating that the expression of CIP4 increased in the tubular epithelia of 5/6-nephrectomized rats and TGF-β1 treated HK-2 cells. Endogenous CIP4 evidenced punctate localization throughout the cytosol, with elevated levels observed in the perinuclear region of HK-2 cells. Subsequent to TGF-β1 treatment, CIP4 expression increased, forming clusters at the cell periphery that gradually redistributed into the cytoplasm. Simultaneously, EMT induction in cells was confirmed by the prevalence of morphological changes, loss of E-cadherin, increase in α-SMA expression, and secretion of fibronectin. Overexpression of CIP4 promoted characteristics similar to those commonly observed in EMT, and small interfering RNA (siRNA) molecules capable of CIP4 knockdown were used to demonstrate reversed EMT. Cumulatively, results of the current study suggest that CIP4 promotes TGF-β1-induced EMT in tubular epithelial cells. Through this mechanism, CIP4 is capable of inducing ECM deposition and exacerbating progressive fibrosis in chronic renal failure.

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Erbin, a member of LAP family, is recently reported to inhibit Smads and ERK pathway which are two important types of intracellular signaling involved in TGF-β1-induced EMT. However, the role of Erbin in the regulation of EMT and the underlying mechanisms remain to be fully understood. To that end, we aimed to evaluate the expression of Erbin in renal interstitial fibrosis and the potential role of Erbin in tubular EMT stimulated by TGF-β1. In this study we demonstrated that the expression of Erbin was upregulated in the tubular epithelia of 5/6-nephrectomized rats. We also showed here that TGF-β1 upregulated Erbin expression in NRK52E cells during their EMT phenotype acquisition. Importantly, elevated expression of Erbin inhibited ERK signaling and partial reversed EMT stimulated by TGF-β1. In the mean time, reducing Erbin expression enhanced ERK phosphorylation, promoted the E-cadherin suppression, and induced α-SMA expression and fibronection secretion in response to TGF-β1, which could be rescued if cells were treated with the inhibitor of MEK1/2 U0126. However, in the absence of TGF-β1, Erbin failed to affect ERK activation and EMT process. These results suggest that Erbin is a negative feedback molecule induced by TGF-β1 and inhibits TGF-β1-induced EMT via ERK signaling pathway.

Erbin, a member of Leucine-rich repeat and PDZ-containing protein family, was found to inhibit TGF-β-induced epithelial-mesenchymal transition (EMT) in our previous study. However, the mechanism of Erbin in regulating EMT is unclear. Semaphorin protein Sema4C, with PDZ binding site at C-terminal has been recognized as a positive regulator of EMT. Here, we aimed to examine the interaction between Erbin and Sema4C. HK2 cells were treated with TGF-β1, or transfected with Erbin and (or) Sema4C. Interaction of Erbin and Sema4C was identified by immunoprecipitation. RT-PCR was used to detect the expression of Erbin and Sema4C at mRNA level after transfection. The expression levels of Erbin, Sema4C, and markers of EMT were measured by using Western blotting or ELISA. After HK2 cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the protein expression levels of Erbin and Sema4C were both up-regulated, and immunoprecipitation results showed Erbin interacted with Sema4C in HK2 cells both at endogenous and exogenous levels. Furthermore, overexpression of Sema4C suppressed E-cadherin, induced vimentin and promoted fibronectin secretion, indicating Sema4C promotes the process of EMT. However, HK2 cells overexpressing Erbin were resistant to Sema4C-induced EMT. In contrast, Erbin specific siRNA promoted EMT induced by Sema4C. Taken together, these results suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced EMT.