Renal Cortex Research Articles

Evaluation of Robustness of S-Transform Based Phase Velocity Estimation in Viscoelastic Phantoms and Renal Transplants.

Ultrasound shear wave elastography (SWE) methods are being used to differentiate healthy versus diseased tissue on the basis of their viscoelastic mechanical properties. Tissue viscoelasticity is often studied by analyzing shear wave phase velocity dispersion curves, which is the variation of phase velocity with frequency or wavelength. Recently, a unique approach using a generalized Stockwell transformation (GST-SFK) was proposed for the calculation of dispersion curves in viscoelastic media over expanded frequency band. In this work, the method's robustness was evaluated on data from five custom-made viscoelastic tissue-mimicking phantoms and sixty in vivo renal transplants. For each phantom, 15 shear wave motion data acquisitions were taken, while 10-13 acquisitions were acquired for renal transplants measured in the renal cortex. For each data-set mean and standard deviation (SD) of estimated phase velocity dispersion curves were studied. In addition, the viscoelastic parameters of the Zener model were examined, which were preceded by a convergence analysis. For viscoelastic phantoms scanned with a research ultrasound scanner, and for the in vivo renal transplants scanned with a clinical scanner, the decisive advantage of the GST-SFK method over the standard two-dimensional Fourier transform (2D-FT) method was shown. The GST-SFK method provided dispersion curve estimates with lower SD over a wider frequency band in comparison to the 2D-FT method. These advantages are relevant to the analysis of the mechanical properties of tissues in clinical practice to discriminate healthy from diseased tissue.

Imaging of Perirenal and Intrarenal Lymphatic Vessels: Anatomy-based Approach.

The lymphatic system (or lymphatics) consists of lymphoid organs and lymphatic vessels. Despite the numerous previously published studies describing conditions related to perirenal and intrarenal lymphoid organs in the radiology literature, the radiologic findings of conditions related to intrarenal and perirenal lymphatic vessels have been scarcely reported. In the renal cortex, interlobular lymphatic capillaries do not have valves; therefore, lymph can travel along the primary route toward the hilum, as well as toward the capsular lymphatic plexus. These two lymphatic pathways can be opacified by contrast medium via pyelolymphatic backflow at CT urography, which reflects urinary contrast agent leakage into perirenal lymphatic vessels via forniceal rupture. Pyelolymphatic backflow toward the renal hilum should be distinguished from urinary leakage due to urinary injury. Delayed subcapsular contrast material retention via pyelolymphatic backflow, appearing as hyperattenuating subcapsular foci on CT images, mimics other subcapsular cystic diseases. In contrast to renal parapelvic cysts originating from the renal parenchyma, renal peripelvic cysts are known to be of lymphatic origin. Congenital renal lymphangiectasia is mainly seen in children and assessed and followed up at imaging. Several lymphatic conditions, including lymphatic leakage as an early complication and acquired renal lymphangiectasia as a late complication, are sometimes identified at imaging follow-up of kidney transplant. Lymphangiographic contrast material accumulation in the renal hilar lymphatic vessels is characteristic of chylo-urinary fistula. Chyluria appears as a fat-layering fluid-fluid level in the urinary bladder or upper urinary tract. Recognition of the anatomic pathway of tumor spread via lymphatic vessels at imaging is of clinical importance for accurate management at oncologic imaging. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Ameliorative effects of thymoquinone on the caspase 3, kidney function and oxidative stress tartrazine-induced nephrotoxicity

First in the literature this study aimed to investigate the effects of Tartrazine, a common industrial food dye, on kidney and whether Thymoquinone has a protective effect in tartrazine-induced nephrotoxicity. The study conducted on the rats bred at İnönü University Experimental Animals Production and Research Center. Wistar albino rats were randomly divided into 4 groups, where each group included 8 rats: control, Tartrazine, Thymoquinone, and Tartrazine + Thymoquinone groups. The experiments continued for 3 weeks and then, kidney tissues and blood samples were collected from the rats under anesthesia. Malondialdehyde (MDA), super oxidized dismutase (SOD), total oxidant status (TOS), increase in Oxidative stress index (OSI), glutathione (GSH), Glutathione peroxidase (GSH-Px), catalase (CAT), Total antioxidant status (TAS) levels decreased in the kidney tissues collected from the tartrazine group. Serum Bun and Creatinine levels increased in the tartrazine group. Tartrazine administration damaged and degenerated the glomeruli and cortical distal tubes in the histopathology of kidney tissues, also different degrees of inflammatory cell infiltration were observed in the renal cortex and medulla. Thymoquinone and tartrazine administration improved both biochemical and histopathological parameters. Tartrazine administration induced nephrotoxicity. This could be observed with the increase in oxidant capacity and the deterioration of kidney functions. Thymoquinone was observed to demonstrate strong antioxidant properties. Thymoquinone could be used primarily as a protective agent against Tartrazine-induced toxicity.

Morphological characteristics of the kidneys of mature dogs (Canis Lupus Familiaris L., 1758)

Each biological species of animals is unique in its structure, which is due to the uniqueness of ecological habitats and the peculiarities of adaptation of homeostasis mechanisms to the influence of environmental factors. Subtle differences in the structural and functional components of organs found in different species of animals create a clear architecture for understanding the depth of biological processes. Research of species, breed and age macro- and microanatomical structures and their morphometric indicators of organs and systems should be considered as urgent tasks of modern morphology. The new data on the morphological indicators of organs discovered at the macro- and micro-levels make a certain contribution to the age-related, breed-related, comparative, experimental and clinical morphology of mammals. Urinary organs in the body of mammals play one of the leading roles in maintaining the physiological and biochemical status of the organism and homeostasis as a whole, which largely depends directly on the morphological and functional state of these organs. Increasingly, there is a need for comprehensive scientific studies of various departments of the urinary organs. The scientific article uses material that is a fragment of the planned research work of the department of normal and pathological morphology, hygiene and expertise “Development, morphology and histochemistry of animal organs in normal and pathological conditions”, state registration number 0120U100796. The article contains the results of the morphometric characteristics of the kidneys of sexually mature dogs – Canis lupus familiaris L., 1758. During the implementation of this work, complex research methods were applied: anatomical, histological, morphometric and statistical. For histological examination, a fragment of kidneys was selected, they were fixed in 10 % neutral formalin solution, Carnois and Buena fluid. In the future, dehydration was carried out in alcohols of increasing concentration and the procedure for sealing the organ was carried out according to generally accepted methods. Using a sled microtome, histological sections with a thickness of 7–10 μm were obtained. Processing of the results of histological sections was examined under a “Micros” light microscope with a digital camera at a magnification of × 100–400. The morphological study of the structural organs of the urinary system was studied on histological sections by the method of light microscopy in accordance with the requirements of the international principles of the “European Convention for the Protection of Vertebrate Animals Used in Experiments and Other Scientific Purposes” (Strasbourg, 1986), by the decision of the First National Congress on Bioethics (M. Kyiv, 2001), Law of Ukraine No. 692 “On the Protection of Animals from Cruel Treatment” (3447-IV) dated February 21, 2006. According to the histological structure, the kidneys of dogs are represented by renal corpuscles and renal tubules, which are made of epithelial cells. Organometric studies indicate that the absolute mass of kidneys in sexually mature dogs is 119.8 ± 6.48 g, relative – 0.74 ± 0.04 %. Morphometric studies of the kidney parenchyma in dogs have established that the average area of renal corpuscles is 4.89 ± 0.24 thousand μm², the area of the vascular glomerulus is 3.79 ± 0.18 thousand μm², the area of the Shumlyansky-Bowman capsule lumen is 1.12 ± 0.27 thousand μm². The average volume of renal bodies of the cortical substance is 1265.69 ± 239.34 thousand μm³. The number of renal corpuscles per conventional unit of area (5 mm²) is 20.8 ± 0.6 units. The aim of the work was to investigate the peculiarities of the morphogistological structure of the kidneys of sexually mature dogs. The research results will expand information about the morphological structure, and will serve for the development of issues of physiology, pathology and treatment of diseases of the urinary organs.

Depiction rate of feeding arteries of renal cell carcinoma on four-dimensional computed tomography angiography

PurposeTo retrospectively evaluate the depiction rate of feeding arteries in biopsy-proven clear cell renal cell carcinoma (CCRCC) on four-dimensional computed tomography angiography (4D-CTA) images.Materials and methodsThis study included 22 patients with 22 CCRCC and 30 feeding arteries treated with transcatheter renal artery embolization. The depiction rate of the feeding arteries on preprocedural 4D-CTA was evaluated. Images were acquired by 320-row multi-detector computed tomography (CT) 15‒36 s after starting to inject a contrast agent (600 mg/kg iodine) intravenously into patients at 2.1 s intervals (11 phases). Two board-certified radiologists retrospectively assessed the feeder depiction rate in all 11 phases with reference to the procedural images as the gold standard. Discrepancies were resolved by consultation with a third radiologist.ResultsAmong the feeders, 11 (36.7%) were segmental or lobar, and 19 (63.3%) were interlobar or arcuate arteries. The feeder depiction rate was the highest (25 [83.3%] of 30) in the 5th phase (delay, 23.4 s) where the gap in contrast enhancement between the renal artery and cortex was the largest. This was followed by the 6th (23 [76.7%] of 30), 4th (22 [73.3%] of 30]), and 7th (21 [70.0%] of 30) phases. The overall rate of depicting feeding arteries in the 11 phases of 4D-CTA was 28 (93.3%) of 30.ConclusionsThe depiction rate of CCRCC feeding arteries including lobar or smaller artery branches by 4D-CTA was favorable. The feeding arteries were optimally visualized during the phase with the largest contrast gap between the renal artery and cortex.

Multiomics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. As many genes associate with DKD, multi-omics approaches were employed to narrow the list of functional genes, gene products and related pathways providing insights into the pathophysiological mechanisms of DKD. The Kidney Precision Medicine Project human kidney single-cell RNA-sequencing (scRNAseq) dataset and Mendeley Data on human kidney cortex biopsy proteomics were utilized. R package Seurat was used to analyze scRNAseq and subset proximal tubule cells. PathfindR was applied for pathway analysis in cell type-specific differentially expressed genes and R limma package was used to analyze differential protein expression in kidney cortex. A total of 790 differentially expressed genes were identified in proximal tubule cells, including 530 upregulated and 260 downregulated transcripts. Compared with differentially expressed proteins, 24 genes/proteins were in common. An integrated analysis combining protein quantitative trait loci (pQTL), GWAS hits (estimated glomerular filtration rate) and a plasma metabolomics analysis was performed using baseline metabolites predictive of DKD progression in our longitudinal Diabetes Heart Study samples. Aldo-keto reductase family 1 member A1 gene (AKR1A1) was revealed as a potential molecular hub for DKD cellular dysfunction in several cross-linked pathways featured by deficiency of this enzyme.

Human soluble prorenin receptor expressed in mouse renal collecting duct shows sex-specific effect on cardiorenal function.

Soluble prorenin receptor (sPRR), a component of the renin-angiotensin system (RAS), has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. Despite studies showing that sPRR in the kidney is produced by tubular cells in the renal collecting duct (CD), its biological actions modulating cardiorenal function in physiological conditions remain unknown. Therefore, the objective of our study was to investigate whether CD-derived human sPRR (HsPRR) expression influences cardiorenal function and examine sex and circadian differences. Thus, we investigated the status of the intrarenal RAS, water and electrolyte balance, renal filtration capacity, and blood pressure (BP) regulation in CD-HsPRR and control (CTL) mice. CD-HsPRR mice were generated by breeding human sPRR-Myc-tag mice with Hoxb7/Cre mice. Renal sPRR expression increased in CD-HsPRR mice, but circulating sPRR and RAS levels were unchanged compared with CTL mice. Only female littermates expressing CD-HsPRR showed 1) increased 24-h BP, 2) an impaired BP response to an acute dose of losartan and attenuated angiotensin II (ANG II)-induced hypertension, 3) reduced angiotensin-converting enzyme activity and ANG II content in the renal cortex, and 4) decreased glomerular filtration rate, with no changes in natriuresis and kaliuresis despite upregulation of the β-subunit of the epithelial Na+ channel in the renal cortex. These cardiorenal alterations were displayed only during the active phase of the day. Taken together, these data suggest that HsPRR could interact with ANG II type 1 receptors mediating sex-specific, ANG II-independent renal dysfunction and a prohypertensive phenotype in a sex-specific manner.NEW & NOTEWORTHY We successfully generated a humanized mouse model that expresses human sPRR in the collecting duct. Collecting duct-derived human sPRR did not change circulating sPRR and RAS levels but increased daytime BP in female mice while showing an attenuated angiotensin II-dependent pressor response. These findings may aid in elucidating the mechanisms by which women show uncontrolled BP in response to antihypertensive treatments targeting the RAS, improving approaches to reduce uncontrolled BP and chronic kidney disease incidences in women.

Quantitative studies on B-mode ultrasound and point shear wave elastography of kidneys in nonazotemic dogs.

Renal diseases in dogs can be diagnosed effectively using B-mode ultrasound. Point shear wave elastography (pSWE) has demonstrated usefulness in diagnosing renal diseases in human medicine. However, its application in veterinary medicine is in its nascent stage. It was hypothesized that establishing pSWE reference values in nonazotemic dogs would prove valuable in differentiating renal diseases. In light of this, a single-center, quantitative study with an objective to normalize B-mode ultrasound parameters and pSWE values of the kidney in nonazotemic dogs was conducted. A total of 198 animals presented with clinical signs of anorexia, vomiting, weight loss, and dehydration were enrolled in the study spanning 2 years. Among them, 52 nonazotemic dogs were included as subjects for the study. B-mode ultrasound quantitative parameters, including length (L), breadth (B), height (H), cortical thickness (RCT), and medulla thickness (RMT) of the kidneys, as well as the diameter of the aorta (Ao), were normalized. Additionally, calculated parameters such as L:Ao, B:Ao, H:Ao, RCT:Ao, and corticomedullary ratios were worked out. Point shear wave elastography values were obtained from the cranial and caudal poles of renal cortices using ElastPQ stiffness software. The pSWE values of kidneys in nonazotemic dogs were normalized. The mean±standard error values were 1.04±0.08m/s (95% confidence interval: 0.88-1.19m/s) and 4.18±0.62kPa (95% confidence interval: 2.93-5.42kPa). In conclusion, B-mode ultrasound quantitative parameters, ratios, and pSWE values were normalized in nonazotemic dogs, which may prove valuable in differentiating renal pathologies in canine patients.

Disulfideptosis-associated lncRNAs reveal features of prognostic, immune escape, tumor mutation, and tumor malignant progression in renal clear cell carcinoma.

Investigating the role of lncRNAs associated with the latest cell death mode (Disulfideptosis) in renal clear cell carcinoma, as well as their correlation with tumor prognosis, immune escape, immune checkpoints, tumor mutational burden, and malignant tumor progression. Searching for potential biomarkers and targets for renal clear cell carcinoma. Downloaded the expression profile data and clinical data of 533 cases of renal clear cell carcinoma from the TCGA database, and randomly divided them into a test set (267 cases) and a validation set (266 cases). Based on previous research, 13 genes associated with Disulfideptosis were obtained. Using R software, lncRNAs with a differential expression that is related to the prognosis of renal clear cell carcinoma and associated with Disulfideptosis were screened out. After univariate Cox regression analysis, Lasso regression analysis, and multivariate Cox regression analysis, lncRNAs with independent predictive ability were obtained. A predictive risk model was established based on the risk scores. Verification was carried out between the obtained high-risk and low-risk groups and their subgroups (including Age, Gender, tumor mutational burden (TMB), tumor grading, and staging). Subsequently, a nomogram was established, and a calibration curve was generated for verification. Performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. Downloaded the values of Tumor Immune Dysfunction and Exclusion (TIDE) for all samples and calculated the difference between the high and low-risk groups. Selected human renal tumor cell lines (786-O, OS-RC-2, A-498, ACHN) and human renal cortex proximal tubule epithelial cell line (HK-2). The RNA expression levels of the above lncRNAs in each cell line were analyzed using RT-qPCR (Real-time Quantitative PCR Detecting System). Used siRNA (small interfering RNA) to knock down FAM225B in 786-O and OS-RC-2 cell lines, and then performed in vitro cell experiments to validate the functional characteristics of FAM225B. Our constructed predictive model includes 5 lncRNAs with an independent predictive ability (FAM225B, ZNF503-AS1, SPINT1-AS1, WWC2-AS2, LINC01338), which can effectively distinguish between patients in high and low-risk groups and their subgroups. The 1, 3, and 5-year AUC (Area Under the ROC Curve) values of the established nomogram are 0.756, 0.752, and 0.781, respectively. The 5-year AUC value is higher compared to other clinical characteristics (Age: 0.598, Gender: 0.488, Grade: 0.680, Stage: 0.717). After the knockdown of FAM225B, the proliferation, migration, and invasion abilities of renal cancer cell lines OS-RC-2 and 786-O all decreased. We have constructed and validated a prognostic model based on Disulfideptosis-associated lncRNAs. This model can effectively predict the high or low risk of patient prognosis and can distinguish the tumor cell mutational burden and immune escape capabilities among high-risk and low-risk patients. This predictive model can serve as an independent prognostic factor for renal clear cell carcinoma, providing a new direction for personalized treatment of patients with renal clear cell carcinoma.

A comparative modeling study of the mitochondrial function of the proximal tubule and thick ascending limb cells in the rat kidney.

To reabsorb >99% of the glomerular filtrate, the metabolic demand of the kidney is high. Interestingly, renal blood flow distribution exhibits marked inhomogeneity, with typical tissue oxygen tension (Po2) of 50-60 mmHg in the well-perfused cortex and 10-20 mmHg in the inner medulla. Cellular fluid composition and acidity also varies substantially. To understand how different renal epithelial cells adapt to their local environment, we have developed and applied computational models of mitochondrial function of proximal convoluted tubule cell (baseline Po2 = 50 mmHg, cytoplasmic pH = 7.20) and medullary thick ascending limb (mTAL) cell (baseline Po2 = 10 mmHg, cytoplasmic pH = 6.85). The models predict key cellular quantities, including ATP generation, P/O (phosphate/oxygen) ratio, proton motive force, electrical potential gradient, oxygen consumption, the redox state of key electron carriers, and ATP consumption. Model simulations predict that close to their respective baseline conditions, the proximal tubule and mTAL mitochondria exhibit qualitatively similar behaviors. Nonetheless, because the mTAL mitochondrion has adapted to a much lower Po2, it can sustain a sufficiently high ATP production at Po2 as low as 4-5 mmHg, whereas the proximal tubule mitochondria would not. Also, because the mTAL cytosol is already acidic under baseline conditions, the proton motive force (pmf) exhibits higher sensitivity to further acidification. Among the different pathways that lead to oxidative phosphorylation impairment, the models predict that both the proximal tubule and mTAL mitochondria are most sensitive to reductions in Complex III activity.NEW & NOTEWORTHY Tissue fluid composition varies substantially within the mammalian kidney. The renal cortex is well perfused and pH neutral, whereas some medullary regions are hypoxic and acidic. How do these environments affect the mitochondrial function of proximal convoluted tubule and medullary thick ascending limb cells, which reside in the cortex and medulla, respectively? This computational modeling study demonstrates that these mitochondria can adapt to their contrasting environments and exhibit different sensitivities to perturbations to local environments.

Bioinspired BSA@polydopamine@Fe Nanoprobe with Self-Purification Capacity for Targeted Magnetic Resonance Imaging of Acute Kidney Injury.

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.

Imaging Characteristics of Clear Cell Papillary Renal Cell Carcinoma: Identifying the Sheep in Wolf's Clothing.

This study aimed to describe the characteristics of computed tomography (CT) and magnetic resonance imaging (MRI) of clear cell papillary renal cell carcinoma (CCPRCC). This retrospective study comprised 27 patients diagnosed with 29 tumors of CCPRCC. The study was approved by the Medical Ethics Committee and the requirement for the informed consent was waived. The inclusion criteria stipulated pathology-confirmed CCPRCCs with at least one preoperative imaging examination, including CT or MRI. Two experienced radiologists independently analyzed the imaging characteristics, including size, location, growth mode, morphology, texture, density, and enhancement pattern. Paired t-test was used to compare differences in CT Hounsfield unit values and apparent diffusion coefficient (ADC) imaging between the tumor and the renal cortex. The mean age of the 27 patients was 57.0 ± 14.2 years. Nineteen patients underwent CT, while 12 underwent MRI (There are 4 patients underwent not only CT but also MRI). Among the cases, 26 (96%) were single, and 1 (4%) was multiple, consisting of three lesions. Out of the 29 tumors, 15 (52%) were located in the left kidney and 14 (48%) in the right kidney. The mean tumor diameter was 3.3 ± 1.7 cm. Furthermore, 19 (66%), 3 (10%), and 7 (24%) tumors were solid, cystic, mixed solid, and cystic type, respectively. The growth mode was endogenous and exogenous in 8 (28%) and 21 (72%) tumors, respectively. The tumor shape was irregular and round in 5 (17%) and 24 (83%) tumors, respectively. The CT value of the tumor was approximately 33.2 ± 9.8 HU, which was not significantly different from that of the renal cortex(31.1 ± 6.3HU)(p = 0.343). Furthermore, 7 (24%), 12 (41%), and 3 (10%) had calcification, cystic degeneration, and hemorrhage, respectively. In 12 tumors, hypointense and hyperintense were predominant on T1 and T2-weighted images, respectively. The tumor capsule was found at the edge of 12 tumors. The average ADC value of the tumor (1.54 ± 0.74 × 10-3 mm2/s) and that of the renal cortex(1.68 ± 0.63×10-3mm2 /s) was not statistically significantly different (p = 0.260). The enhancement scanning revealed "wash-in and wash-out" enhancement in 19 (68%) tumors, continuous or progressive enhancement in 6 (21%) tumors, and enhanced cystic wall and central separation in 3 (11%) tumors. CCPRCC occurs more likely in middle-aged and elderly individuals, and the tumor is prone to cystic degeneration, with rare bleeding and calcification, and no obvious limitation on MRI diffusion-weighted imaging, which enhancement form performs as mainly "wash-in and washout," but the final diagnosis depends on histopathology.

Spatial analysis of renal acetaminophen metabolism and its modulation by 4-methylpyrazole with DESI mass spectrometry imaging.

Acute kidney injury (AKI) is a common complication in acetaminophen (APAP) overdose patients and can negatively impact prognosis. Unfortunately, N-acetylcysteine, which is the standard of care for the treatment of APAP hepatotoxicity does not prevent APAP-induced AKI. We have previously demonstrated the renal metabolism of APAP and identified fomepizole (4-methylpyrazole, 4MP) as a therapeutic option to prevent APAP-induced nephrotoxicity. However, the kidney has several functionally distinct regions, and the dose-dependent effects of APAP on renal response and regional specificity of APAP metabolism are unknown. These aspects were examined in this study using C57BL/6J mice treated with 300-1200 mg/kg APAP and mass spectrometry imaging (MSI) to provide spatial cues relevant to APAP metabolism and the effects of 4MP. We find that renal APAP metabolism and generation of the nonoxidative (APAP-GLUC and APAP-SULF) and oxidative metabolites (APAP-GSH, APAP-CYS, and APAP-NAC) were dose-dependently increased in the kidney. This was recapitulated on MSI which revealed that APAP overdose causes an accumulation of APAP and APAP GLUC in the inner medulla and APAP-CYS in the outer medulla of the kidney. APAP-GSH, APAP-NAC, and APAP-SULF were localized mainly to the outer medulla and the cortex where CYP2E1 expression was evident. Interestingly, APAP also induced a redistribution of reduced GSH, with an increase in oxidized GSH within the kidney cortex. 4MP ameliorated these region-specific variations in the formation of APAP metabolites in renal tissue sections. In conclusion, APAP metabolism has a distinct regional distribution within the kidney, the understanding of which provides insight into downstream mechanisms of APAP-induced nephrotoxicity.

Effect of Solanum melongena on Components and Kidney Damage of Fructose-Induced Metabolic Syndrome in Rats

: In traditional Mexican medicine, Solanum melongena is used to treat obesity, diabetes mellitus, hypertension, asthma, bronchitis, arthritis, and hypercholesterolemia. This study examined the effect of treatment with ethanolic extract (EE) from the fruit of S. melongena on kidney damage on metabolic syndrome (MS). Male Wistar rats were maintained for 12 weeks on a diet of 20% fructose in drinking water and chow to develop MS. After administering EE of S. melongena (100 and 200 mg/kg/day, orally) for 6 weeks, the histological study of the kidney cortex and determination by Western blot of the renal expression of angiotensin II AT1 receptor and cytokine transforming growth factor beta 1 (TGF-β1) were realized. The rats fed with high fructose developed MS and showed kidney damage characterized by proliferative glomerulonephritis and necrosis; this damage was reduced by S. melongena treatment and associated with decreased expression of AT1 receptor for angiotensin II and cytokine TGF-β1, controlling renal damage in this animal model. In rats affected by MS through high fructose feeding, the treatment with EE of S. melongena showed a renoprotective effect through decreased expression of AT1 receptor for angiotensin II and cytokine TGF-β1, causes of glomerulonephritis.

Effect of Zoapatle (Montanoa tomentosa) on Inflammatory Markers in a Murine Model of Ventricular Hypertrophy

Zoapatle, a native plant utilized for centuries in traditional Mexican medicine, is abundantly found in Mesoamerica and northern South America. Pleiotropic effects of this genus have been recognized, primarily inducing alterations in smooth muscle contractility in animal models. The aim of this study was to evaluate the effect of Zoapatle on the hypertrophy index and the gene expression of TNF-α, IL-1β, NF-κB, STAT5, and the PRLR in the brain, left ventricle, and renal cortex of rats with isoproterenol-induced cardiac hypertrophy. Three groups were studied, the control group (n = 4), hypertrophy group (n = 4) and hypertrophy group treated with Zoapatle (n = 4). A ventricular hypertrophy model was developed with 150 mg/kg/day of isoproterenol intraperitoneally administered over two days with a 24 h interval between applications. Zoapatle was administered for 28 consecutive days (25 mg/kg). Gene expression was determined with RT-qPCR. Subsequently, a principal component analysis (PCA) was performed using the RNA expression variables. A notably reduced left ventricle mass index was observed in the Zoapatle group. Additionally, Zoapatle administration in cardiac hypertrophy demonstrated a significant decrease in the gene expression of TNF-α, IL-1B, STAT 5, and the PRLR. TNF-α and the transcription factor STAT5 exhibited a similar trend in both the left ventricle and renal cortex, suggesting a correlation with the inflammatory state in these tissues due to ventricular hypertrophy. The findings suggest that Zoapatle reverses the hypertrophy index in a hypertrophy model, concurrently reducing several proinflammatory mediators associated with the hypertrophy index.

Effect of Respiratory Failure on Peripheral and Organ Perfusion Markers in Severe COVID-19: A Prospective Cohort Study.

Microvascular dysfunction and inflammation caused by COVID-19 disrupt organ function. The study aimed to investigate the association between the severity of SARS-CoV-2 pneumonia and peripheral and organ perfusion as a consequence of altered microcirculation. A total of 116 patients hospitalized due to severe COVID-19 were enrolled in the study. On admission, the patients underwent a Capillary Refill Time (CRT) examination, finger oxygen saturation measurement, thermal imaging of the hand (FIT), and a kidney Doppler ultrasound. Medical data were collected from the medical history. From the evaluated perfusion parameters, only renal cortex perfusion (RCP) was substantially correlated with the CT score (p < 0.010). The peripheral perfusion parameters of Sat., FIT, CRT, and RCP correlated with the ARDS stages (p = 0.0021; p = 0.038; p < 0.0006; p < 0.0002, respectively). The Oxygenation Ratio value (p < 0.001) was significantly associated with all the perfusion parameters (saturation, CRT, FIT, and RCP) in the multivariable regression analysis model. According to the stepwise retrograde regression analysis, RCP was an independent parameter linked with the Oxygenation Ratio (p < 0.001). Severe COVID-19 can result in microvascular dysfunction influencing peripheral and organ perfusion, which can be measured with various methods. The staging of COVID-19 assessed by CT and the Oxygenation Ratio correlates with RCP, CRT, FIT, and oxygen saturation.

GIANT HYDRONEPHROSIS DUE TO URETEROPELVIC JUNCTION STENOSIS IN PEDIATRICS: A RARE CASE

Objective: This case report presented giant hydronephrosis (GH) due to Ureteropelvic Junction Stenosis in pediatrics. Case(s) Presentation: A three-year-old boy was admitted with abdominal distension and pain for the last three month. CT scan without contrast of the abdomen showed a left kidney size of 141x 97x 63.5 mm, massive dilatation of the pelvicalyceal system, thinning cortex in the left kidney, and left ureter measurement of 16 mm in diameter. An urgent percutaneous nephrostomy tube (10Fr) was placed in the left kidney for this patient, followed by a pyeloplasty procedure in the next three weeks. The patient was discharged on day five, and the six-month follow-up results were good. Discussion: Giant Hydronephrosis is a rare entity, with less than 500 global cases reported in the literature. The diagnostic approach to suspected hydronephrosis in pediatrics is sonography and may be followed by CT or MRI. Management of giant hydronephrosis requires two stages procedure with percutaneous nephrostomy followed by pyeloplasty. This two-stage method ensure the renal function is preserved. Conclusion: Ureteropelvic Junction Stenosis is a common cause of giant hydronephrosis in pediatrics. Appropriate physical examination and other diagnostic approaches are needed to diagnose patients with giant hydronephrosis and determine the best management.&#x0D; Keywords: Giant hydronephrosis, ureteropelvic junction stenosis, pyeloplasty.

Immunoaffinity proteomics for kidney injury biomarkers in male beagle dogs.

Drug-induced kidney injury (DIKI) is a cause of drug development failure. Dogs represent a common non-rodent animal model in pre-clinical safety studies; however, biomarker assays for detecting nephrotoxicity in dogs are limited. To identify novel proteins and gain insight into the molecular mechanisms involved in DIKI, we developed an assay to evaluate proteomic changes associated with DIKI in male beagle dogs that received nephrotoxic doses of tobramycin for 10 consecutive days. Label-free quantitative discovery proteomics analysis on representative kidney cortex tissues collected on Day 11 showed that the tobramycin-induced kidney injury led to a significant differential regulation of 94 proteins mostly associated with mechanisms of nephrotoxicity such as oxidative stress and proteasome degradation. For verification of the proteomic results, we developed a multiplex peptide-centric immunoaffinity liquid chromatography tandem mass spectrometry assay (IA LC-MS/MS) to evaluate the association of eight DIKI protein biomarker candidates using kidney cortices collected on Day 11 and urine samples collected on Days -4, 1, 3, 7 and 10. The results showed that most biomarkers evaluated were detected in the kidney cortices and their expression profile in tissue aligned with the label-free data. Cystatin C was the most consistent marker regardless of the magnitude of the renal injury while fatty acid-binding protein-4 (FABP4) and kidney injury molecule-1 (KIM-1) were the most affected biomarkers in response to moderate proximal tubular injury in absence of changes in serum-based concentrations of blood urea nitrogen or creatinine. In the urine, clusterin is considered the most consistent biomarker regardless of the magnitude and time of the renal injury. To our knowledge, this is the most comprehensive multiplex assay for the quantitative analysis of mechanism-based proximal tubular injury biomarkers in dogs.

T1 mapping combined with arterial spin labeling MRI to identify renal injury in patients with liver cirrhosis.

We investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis. We recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values were measured from the renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed. Cortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = -0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis. Renal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis.

Analysis of fetal renal cortex development: Cortical maturation index as a new potential guide in fetal renal cortex assessment

Background/Aim. To date, most of the scientific attention has been aimed at the morphometric analysis of the nephrogenic zone (NZ) of the fetal renal cortex, while the quantification and analysis of the maturation zone (MZ) and other indicators of renal maturity were missing. The aim of the study was to examine the characteristics of fetal kidney cortex maturation, as well as to propose the development of a new cortical maturity index (CMI). Methods. The study included 42 paraffin molds of the fetal kidney, divided into three groups according to gestational age (GA). After hematoxylin and eosin staining, tissue sections were analyzed through the following parameters: the thickness of the NZ and MZ, the renal corpuscles area (RCa) and the glomerular capillary tuft area (GCTa), and the maturation stages of the glomeruli. In addition, a new parameter, CMI, was formed as a ratio of NZ and MZ thickness. The collected data were statistically processed. Results. Changes in NZ and MZ thickness were statistically significant, and they correlated with GA. A value of CMI higher than 0.2 was recorded in the kidney samples of fetuses younger than the 20th gestational week (GW), while a value lower than 0.1 was recorded in the samples older than the 30th GW. With an increase in GA in all zones of the renal cortex, RCa and GCTa decreased. A statistically significant reduction of GCTa was observed in the oldest group in the juxtamedullary and intermediate zones of the cortex (p &lt; 0.01). Glomeruli located in the deeper parts of the cortex were more mature than the superficial ones. Conclusion. The measured parameters can serve as a starting point for future studies that would analyze the histomorphological characteristics of the fetal kidney cortex. In the absence of clinical data, a newly formed parameter CMI can represent assistance with the determination of GA, as it significantly correlates with GA (p &lt; 0.01).