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The purpose of our research was to evaluate Dandelion sterol's treatment effects on diabetes mellitus–induced renal injury in in vitro and in vivo study. The rats were divided into five groups as normal control (Ctrl), diabetic nephropathy model (Model), Dandelion sterol low‐dose treated (Dan‐Low), Dandelion sterol middle‐dose treated (Dan‐Middle), and Dandelion sterol high‐dose treated (Dan‐High). Measuring serum TNF‐α, IL‐1β, and IL‐6 concentrations by Elisa assay, evaluate kidney pathology by HE staining, kidney cell apoptosis of TUNEL, TLR4, and NF‐κB(p65) proteins expression by IHC assay, and relative gene expressions by RT‐qPCR assay. In the following step, using HK‐2 treated with high glucose to model DN cell model to discuss the relative mechanisms, evaluate TNF‐α, IL‐1β, and IL‐6 concentrations by Elisa assay, evaluate cell apoptosis by flow cytometry, evaluate TLR4 and NF‐κB(p65) proteins expression by WB assay, relative gene expression by RT‐qPCR assay, and NF‐κB(p65) nuclear volume by cellular immunofluorescence. Compared with Ctrl group, TNF‐α, IL‐1β, and IL‐6 concentrations and apoptosis cell number were significantly increased, TLR4/NF‐κB(p65) pathway was significantly stimulated in Model rats and cell groups. With Dan supplement, the diabetic‐induced renal injury was significantly improved (p, Dan improved diabetes mellitus‐induced renal injury via regulation of miR‐140‐5p/TLR4 axis in in vitro and in vivo study

Purpose We demonstrate a method of delayed urea differential enhancement CEST for probing urea recycling action of the kidney using expanded multi-pool Lorentzian fitting and apparent exchange-dependent relaxation compensation. Methods T1 correction of urea CEST contrast by apparent exchange-dependent relaxation was tested in phantoms. Nine mice were scanned at 7 Tesla following intraperitoneal injection of 2M 150 μL urea, and later saline. T1 maps and Z-spectra were acquired before and 20 and 40 min postinjection. Z-spectra were fit to a 7-pool Lorentzian model for CEST quantification and compared to urea assay of kidney homogenate. Renal injury was induced by aristolochic acid in 7 mice, and the same scan protocol was performed. Results Apparent exchange-dependent relaxation corrected for variable T1 times in phantoms. Urea CEST contrast at +1 ppm increased significantly at both time points following urea injection in the inner medulla and papilla. When normalizing the postinjection urea CEST contrast to the corresponding baseline value, both urea and saline injection resulted in identical fold changes in urea CEST contrast. Urea assay of kidney homogenate showed a significant correlation to both apparent exchange-dependent relaxation (R2 = 0.4687, P = .0017) and non-T1 -corrected Lorentzian amplitudes (R2 = 0.4964, P = .0011). Renal injury resulted in increased T1 time in the cortex and reduced CEST contrast change upon urea and saline infusion. Conclusion Delayed urea enhancement following infusion can provide insight into renal urea handling. In addition, changes in CEST contrast at 1.0 ppm following saline infusion may provide insight into renal function.

Background Abnormal renal hemodynamic responses to salt‐loading are thought to contribute to salt‐sensitive (SS) hypertension. However, this is based largely on studies in anesthetized animals, and little data are available in conscious SS and salt‐resistant rats. Methods and Results We assessed arterial blood pressure, renal function, and renal blood flow during administration of a 0.4% NaCl and a high‐salt (4.0% NaCl) diet in conscious, chronically instrumented 10‐ to 14‐week‐old Dahl SS and consomic SS rats in which chromosome 1 from the salt‐resistant Brown‐Norway strain was introgressed into the genome of the SS strain (SS.BN1). Three weeks of high salt intake significantly increased blood pressure (20%) and exacerbated renal injury in SS rats. In contrast, the increase in blood pressure (5%) was similarly attenuated in Brown‐Norway and SS.BN1 rats, and both strains were completely protected against renal injury. In SS.BN1 rats, 1 week of high salt intake was associated with a significant decrease in renal vascular resistance (−8%) and increase in renal blood flow (15%). In contrast, renal vascular resistance failed to decrease, and renal blood flow remained unchanged in SS rats during high salt intake. Finally, urinary sodium excretion and glomerular filtration rate were similar between SS and SS.BN1 rats during 0.4% NaCl and high salt intake. Conclusions Our data support the concept that renal vasodysfunction contributes to blood pressure salt sensitivity in Dahl SS rats, and that genes on rat chromosome 1 play a major role in modulating renal hemodynamic responses to salt loading and salt‐induced hypertension.

In hypertension induced by angiotensin II (AngII) administration with high salt (HS) intake, intrarenal angiotensinogen (AGT) and tumor necrosis factor‐alpha (TNF‐α) levels increase. However, TNF‐α has been shown to suppress AGT formation in cultured renal proximal tubular cells. We examined the hypothesis that elevated AngII levels during HS intake reduces TNF‐α receptor type 1 (TNFR1) activity in the kidneys, thus facilitating increased intrarenal AGT formation. The responses to HS diet (4% NaCl) with chronic infusion of AngII (25 ng/min) via implanted minipump for 4 weeks were assessed in wild‐type (WT) and knockout (KO) mice lacking TNFR1 or TNFR2 receptors. Blood pressure was measured by tail‐cuff plethysmography, and 24‐h urine samples were collected using metabolic cages prior to start (0 day) and at the end of 2nd and 4th week periods. The urinary excretion rate of AGT (uAGT; marker for intrarenal AGT) was measured using ELISA. HS +AngII treatment for 4 weeks increased mean arterial pressure (MAP) in all strains of mice. However, the increase in MAP in TNFR1KO (77 ± 2 to 115 ± 3 mmHg; n = 7) was significantly greater (p, We examined the hypothesis that elevated AngII levels during HS intake reduce TNF‐α receptor type 1 (TNFR1) activity in the kidneys, thus facilitating increased intrarenal AGT formation. The responses to HS diet (4% NaCl) with chronic infusion of AngII (25 ng/min) via implanted minipump for 4 weeks were assessed in wild‐type (WT) and knockout (KO) mice lacking TNFR1 and TNFR2 receptors. HS +AngII treatment for 4 weeks increased mean blood pressure (MBP) in all strains of mice. However, the increase in MBP in TNFR1KO was greater than that in WT or in TNFR2KO. The increase in urinary angiotensinogen excretion (UAGT) at the 4th week was also greater in TNFR1KO mice than that in WT or in TNFR2KO mice. The results indicate that TNFR1 activity exerts a protective role by mitigating intrarenal AGT formation induced by elevated AngII and HS intake.

Aims/Introduction Adipose‐derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs. In this study, ASC sheets were directly transplanted into the kidneys of a DN rat model, and therapeutic consequences were analyzed. Materials and Methods Adipose‐derived mesenchymal stem cells were isolated from adipose tissues of 7‐week‐old enhanced green fluorescent protein rats, and ASC sheets were prepared using a temperature‐responsive culture dish. A DN rat model was established from 5‐week‐old Spontaneously Diabetic Torii fatty rats. Seven‐week‐old DN rats (n = 21) were assigned to one of the following groups: sham‐operated (n = 6); ASC suspension (6.0 × 106 cells/mL) administered intravenously (n = 7); six ASC sheets transplanted directly into the kidney (n = 8). The therapeutic effect of the cell sheets was determined based on urinary biomarker expression and histological analyses. Results The ASC sheets survived under the kidney capsule of the DN rat model for 14 days after transplantation. Furthermore, albuminuria and urinary tumor necrosis factor‐α levels were significantly lower in the ASC sheets transplanted directly into the kidney group than in the sham‐operated and ASC suspension administered intravenously groups (P, Adipose‐derived mesenchymal stem cell sheet transplantation enhanced the engraftment efficiency and suppressed the progression of diabetic nephropathy.

Summary The novel coronavirus (SARS‐CoV‐2) has turned into a life‐threatening pandemic disease (Covid‐19). About 5% of patients with Covid‐19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS‐CoV‐2‐induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin‐converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS‐CoV‐2‐driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid‐19 is necessary to develop management strategies and design effective therapies.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.

BACKGROUND Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U-AGT) is a new biomarker gathering attention in many renal diseases. U-AGT reflects intrarenal renin-angiotensin system (RAS) activity. We conducted a study to measure U-AGT in children

INTRODUCTION Contrast induced nephropathy is linked to contrast utilization and strategies for minimizing renal injury are incorporated into many laboratories that perform coronary angiography. Contrast limits have been described, below which there is minimal incremental increase in the risk of renal injury. Whether a priori acknowledgement of these limits as part of a contrast "Time-Out" reduces contrast utilization has not been established. In this study, we investigate the effect of verbalizing pre-angiography and ½ time contrast thresholds on contrast utilization and associated clinical outcomes. METHODS We retrospectively reviewed 5265 cases of coronary angiography (984 with contrast thresholds defined pre-procedure compared to 4281 without pre-defined contrast thresholds). There were two primary endpoints: (1) proportion of procedures that utilized an amount of contrast ≤ threshold, and (2) median difference between amount of contrast utilized and the contrast threshold. Secondary outcomes incorporated indices of renal function, and included changes in serum creatinine levels, eGFR, and CKD stage. RESULTS Compared to pre-"Time-Out" group, the post-"Time-Out" group had a higher proportion of procedures with contrast ≤ stated contrast threshold (88% vs 84%, P

Background Hydroxyethyl-starch (HES) solutions might have renal adverse effects in humans and dogs. Objective To determine if administration of 6% HES-130/0.4 is associated with an increase in serum creatinine concentration and development of acute kidney injury (AKI) in nonazotemic cats. Animals A total of 62 critically ill cats; 26 HES exposed and 36 unexposed. Methods Retrospective cohort study (2012–2015). Serum creatinine concentrations were recorded and changes in serum creatinine concentrations before exposure (baseline) and 2–10 and 11–90 days, respectively, were determined. Development of AKI was defined as a > 150% increase or >26 μmol/L increase in serum creatinine concentration from baseline. Risk factors, such as HES administration, cumulative volume of HES (mL/kg) and number of days of HES administration leading to development of AKI, and change in serum creatinine were analyzed. Results Cats in the HES cohort received a mean volume of 98.5 ± 76.2 mL/kg (range, 8–278 mL/kg) HES over a median of 4 (range, 1–11) days, resulting in a median dose of 20.1 (range, 8–40.5) mL/kg per day. Short-term %change in serum creatinine concentration (P = 0.40) and development of AKI (P = 0.32) were not significantly different between cohorts. Multivariable logistic regression did not identify HES dose in mL/kg (P = 0.33) and number of days of HES application (P = 0.49) as a risk factor for development of AKI. Conclusion and Clinical Importance Hydroxyethyl-starch administration to critically ill nonazotemic cats seems to be safe. A larger prospective study is required to determine the effect of HES administration at higher dosages and for prolonged time periods.

Acid-base homeostasis is an essential process for maintaining proper pH levels in the body, with alterations in this process potentially signaling pathology. While monitoring urine pH, blood gases and other assays can provide information on the overall systemic pH, it is desirable to get more localized knowledge to assist diagnosis. Various non-invasive methods have been developed with Chemical Exchange Saturation Transfer (CEST) MRI now emerging as a particularly intriguing technology for detecting pH. In this review, we provide an overview of the paramagnetic and diamagnetic CEST probes available for producing pH maps, describe in depth the various methods to collect CEST MRI data and post-process the resulting images to create pH maps and describe how this has been applied for detecting renal injury, mapping the pH of tumors and monitoring the health of transplanted therapeutic cells. Finally, we will provide an outlook of the possibilities to translate this technology into patients.

Obesity is a major and independent risk factor of kidney diseases. The pathogenic mechanisms of obesity‐associated renal injury are recognized to at least involve a lipid‐rich and pro‐inflammatory state of the renal tissues, but specific mechanisms establishing causal relation remain unknown. Saturated fatty acids are elevated in obesity, and known to induce chronic inflammation in kidneys. Myeloid differentiation protein 2 (MD2) is an important protein in lipopolysaccharide‐induced innate immunity response and inflammation. We suggested that obesity‐associated renal injury is regulated by MD2 thereby driving an inflammatory renal injury. The used three mouse models for in vivo study: MD2 knockout mice (KO) maintained on high fat diet (HFD), wild‐type mice on HFD plus L6H21, a specific MD2 inhibitor and KO mice given palmitic acid (PA) by IV injection. The in vitro studies were carried out in cultured renal tubular epithelial cells, mouse mesangial cells and primary macrophages, respectively. The HFD mice presented with increased hyperlipidemia, serum creatinine and proteinuria. Renal tissue from HFD mice had increased fibrosis, inflammatory cytokines, macrophage infiltration, and activation of NF‐κB and MAPKs. This HFD‐induced renal injury profile was not observed in KO mice or L6H21‐treated mice. Mice given PA mimmicked the HFD‐induced renal injury profiles, which were prevented by MD2 knockout. The in vitro data further confirmed MD2 mediates PA‐induced inflammation. MD2 is causally related with obesity‐associated renal inflammatory injury. We believe that MD2 is an attractive target for future therapeutic strategies in obesity‐associated kidney diseases.

The activation of transient receptor potential canonical 6 (TRPC6) channel participates in the glomerulosclerosis. The TRPC6 also participates in the mechanical or pressure sensation in various cel...

The chronic angiotensin II (AngII) infusion model is one of the most commonly used to study cardiovascular and kidney injury. However, the dosages of AngII used to induce cardiovascular or renal in...

OBJECTIVES To analyse the contemporary management of renal injuries in a UK major trauma centre and to evaluate the utility and value of re-imaging. PATIENTS AND METHODS The prospectively maintained 'Trauma Audit and Research Network' database was interrogated to identify patients with urinary tract injuries between January 2014 and December 2017. Patients' records and imaging were reviewed to identify injury grades, interventions, outcomes, and follow-up. RESULTS Renal injury was identified in 90 patients (79 males and 11 females). The mean (sd; range) age was 35.5 (17.4; 1.5-94) years. Most of the renal traumas were caused by blunt mechanisms (74%). The overall severity of injuries was: 18 (20%) Grade I, 19 (21%) Grade II, 27 (30%) Grade III, 22 (24%) Grade IV, and four (4%) Grade V. Most patients (84%) were managed conservatively. Early intervention (