Kidney Structure Research Articles

#5453 LIPID NEPHROTOXICITY INDUCED BY HIF-1α ACTIVATION ACCELERATES INTERSTITIAL INJURY IN DIABETIC NEPHROPATHY

Abstract Background and Aims Our previous study demonstrated lipid accumulation contributes to tubulointerstitial injury in diabetic nephropathy. However, the exact mechanism of which accelerate lipid accumulation in tubulointerstitium has not been completely elucidated. Increasing studies suggest that chronic hypoxia plays an important pathophysiologic role in diabetic nephropathy. This study aimed to investigate the effect of hypoxia inducible factor-1α (HIF-1α) activation induced by chronic hypoxia on lipid accumulation in diabetic kidney and to explore its potential mechanism. Method Human proximal tubular cell line HK-2 was incubated with or without cobalt chloride (CoCl2, 100 μM) which stimulates hypoxic condition in the presence or absence of glucose (30 mM) for 24 h. Specific siRNA was transfected in cells to knock down HIF-1α expression. Type 1 diabetic rats model were induced by STZ injection, and Lificiguat (YC-1) was used as HIF-1α inhibitor by intraperitoneal injection. Immunofluorescence staining and Western blot were used to determine the cellular localization and expression of HIF-1α. Periodic Acid-Schiff (PAS) staining was used to observe basic structure and pathological changes of kidney. The expression of carnitine palmitoyl transferase 1A (CPT1A), tissue growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) were measured by immunohistochemical staining and Western blot. Lipid accumulation was detected by oil red O staining and cellular triglyceride quantification assay. Results In in vitro study, CoCl2 effectively increased the expression of HIF-1α and its translocation from cytoplasm to nucleus. Meanwhile, HIF-1α activation induced by CoCl2 significantly increased lipid accumulation in HK-2 cells. Moreover, CoCl2 treatment increased TGF- β and CTGF expression in HK-2 cells. The presence of glucose (30mM) made no significant difference to HK-2 cells incubated with CoCl2. HIF-1α siRNA treatment significantly reduced lipid deposition in HK-2 cells incubated with CoCl2. In vivo study showed YC-1 treatment decreased the expression of HIF-1α in renal tubules of diabetic rats, which was accompanied by less lipid accumulation compared with the diabetes mellitus (DM) group. PAS staining showed the desquamation and necrosis of tubular epithelial cells in the YC-1 group were alleviated compared with the DM group. YC-1 treatment did not affect the ratio of kidney weight to body weight, whereas decreased the levels of blood glucose, urine albumin creatinine ratio and NAG creatinine ratio in diabetic rats. The expressions of fibrosis factor TGF- β and CTGF were decreased in the YC-1 group compared with the DM group. Furthermore, the protein expression of CPT1A, the key enzyme of fatty acid oxidation, which was decreased in the DM group compared with the controls, was regained by YC-1 treatment. Conclusion Our findings demonstrated that HIF-1α activation contributed to interstitial injury in diabetic nephropathy by inducing lipid accumulation. HIF-1α activation might contribute to lipid nephrotoxicity by downregulating fatty acid oxidation.

Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases.

Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive and irreversible loss of kidney function, characterized by fibrosis that could lead to end stage renal disease. In this review we provide a comprehensive overview of the most recent scientific publications analyzing the therapeutic potential of Extracellular Vesicles (EV)-based treatments in different animal models of AKI and CKD. EVs from multiple sources act as paracrine effectors involved in cell-cell communication with pro-generative and low immunogenic properties. They represent innovative and promising natural drug delivery vehicles used to treat experimental acute and chronic kidney diseases. Differently from synthetic systems, EVs can cross biological barriers and deliver biomolecules to the recipient cells inducing a physiological response. Moreover, new methods for improving the EVs as carriers have been introduced, such as the engineering of the cargo, the modification of the proteins on the external membrane, or the pre-conditioning of the cell of origin. The new nano-medicine approaches based on bioengineered EVs are an attempt to enhance their drug delivery capacity for potential clinical applications.

Impact of renal tubular Cpt1a overexpression on the kidney metabolome in the folic acid-induced fibrosis mouse model.

Background: Chronic kidney disease (CKD) is characterized by the progressive and irreversible deterioration of kidney function and structure with the appearance of renal fibrosis. A significant decrease in mitochondrial metabolism, specifically a reduction in fatty acid oxidation (FAO) in tubular cells, is observed in tubulointerstitial fibrosis, whereas FAO enhancement provides protection. Untargeted metabolomics offers the potential to provide a comprehensive analysis of the renal metabolome in the context of kidney injury. Methodology: Renal tissue from a carnitine palmitoyl transferase 1a (Cpt1a) overexpressing mouse model, which displays enhanced FAO in the renal tubule, subjected to folic acid nephropathy (FAN) was studied through a multiplatform untargeted metabolomics approach based on LC-MS, CE-MS and GC-MS analysis to achieve the highest coverage of the metabolome and lipidome affected by fibrosis. The expression of genes related to the biochemical routes showing significant changes was also evaluated. Results: By combining different tools for signal processing, statistical analysis and feature annotation, we were able to identify variations in 194 metabolites and lipids involved in many metabolic routes: TCA cycle, polyamines, one-carbon metabolism, amino acid metabolism, purine metabolism, FAO, glycerolipids and glycerophospholipids synthesis and degradation, glycosphingolipids interconversion, and sterol metabolism. We found several metabolites strongly altered by FAN, with no reversion induced by Cpt1a overexpression (v.g. citric acid), whereas other metabolites were influenced by CPT1A-induced FAO (v.g. glycine-betaine). Conclusion: It was implemented a successful multiplatform metabolomics approach for renal tissue analysis. Profound metabolic changes accompany CKD-associated fibrosis, some associated with tubular FAO failure. These results highlight the importance of addressing the crosstalk between metabolism and fibrosis when undertaking studies attempting to elucidate the mechanism of CKD progression.

The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-β1 signaling in rat.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 μg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1β), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-β1 (TGF-β1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-β1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

Kidney Organoid Derived from Human Pluripotent and Adult Stem Cells for Disease Modeling.

Kidney disease affects a significant portion of the global population, yet effective therapies are lacking despite advancements in identifying genetic causes. This limitation can be attributed to the absence of adequate in vitro models that accurately mimic human kidney disease, hindering targeted therapeutic development. However, the emergence of human induced pluripotent stem cells (PSCs) and the development of organoids using them have opened up a way to model kidney development and disease in humans, as well as validate the effects of new drugs. To fully leverage their capabilities in these fields, it is crucial for kidney organoids to closely resemble the structure and functionality of adult human kidneys. In this review, we aim to discuss the potential of using human PSCs or adult kidney stem cell-derived kidney organoids to model genetic kidney disease and renal cancer.

RENAL12: Can Renal Autologous Cell Therapy (REACT) Delay Dialysis and Renal Transplantation in Chronic Kidney Disease with Type 2 Diabetes? The proact 1 and 2 Phase 3 Trial Design

Introduction: REACT is being developed to preserve renal function and delay or prevent ESRD. REACT is composed of bioactive selected renal cells (SRCs), isolated from a participant’s kidney, which participate in kidney repair and regeneration. Preclinical studies have demonstrated that SRCs injected directly into the kidney cortex produced a regenerative response improving kidney function and structure. Description of therapy REACT is derived from a standard kidney biopsy in an outpatient setting. SRCs are expanded ex vivo, cryopreserved, and shipped to the clinical site approximately 12 weeks later. REACT is percutaneously injected into the kidney cortex utilizing CT guidance in each kidney, 3 months apart. Participants proact 1 and proact will enroll 1200 pts from ~150 sites in the US and ~25 other countries with up to 60 months of follow-up, aged 30-80 years with type 2 diabetes who have an eGFR of 20-50 mL/min/1.73 m2, and UACR 300-5000 mg/g. Eligible participants will be randomized 1:1 to REACT or sham biopsy/injection in a single blind manner. Standard-of-care therapies including RAASi, SGLT2i, and MRAs are given per local guidance. Study Endpoints Time-to-event primary composite endpoint from first injection to the earliest of >≥40% eGFR decline, eGFR < 15 mL/min/1.73m2 sustained for 30 days, initiation of chronic dialysis, kidney transplantation, cardiovascular or renal death. Conclusion:proact 1 and 2 are global phase 3 randomized controlled trials evaluating the safety and efficacy of REACT on major kidney disease endpoints, among participants with type 2 diabetes and Stage 3a/4 CKD. REACT, a novel cell therapy comprised of SRCs, has the potential to directly preserve kidney function with a goal to prevent kidney failure.

Effects of Aqueous Extract of Cumin Seed (Cuminum cyminum) on the Structure and Function of Albino Rat Kidneys Treated with Dibutyl Phthalate

This study was aimed to investigate the effects of Cuminum cyminum seed aqueous extract on the function and histological structure of rat kidney treated with dibutyl phthalate (DBP). Eighteen albino rats weighing 190-240g and aged 10-12 weeks were used for this study which went on for 28 days. The rats were divided into three groups (each with six animals): 1st group: control rats were given food and tap water, 2nd group was given DBP (420mg/Kg. B.W.) with tap water and diet, 3rd group were fed cumin plant orally at a daily dose of (200 mg/kg B.W.) and DBP (420mg/kg. B.W.) was given with drinking water and fed with diet daily. Kidney and liver function parameters were measured and histological structure of kidney was examined. Results showed that DBP significantly increased creatinine, urea as well as liver parameters AST and ALT, while decreased ALP level, destruction, hemorrhage and inflammation in kidney. Cumin decreased AST and ALT level but increased ALP level and elevated kidney hemorrhage which concluded that DBP may cause oxidative stress for rat liver and kidney. Despite hepatoprotective role of cumin, it interacts with DPB and increases bleeding in kidney.

Non-Haemodynamic Mechanisms Underlying Hypertension-Associated Damage in Target Kidney Components.

Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and progression of kidney disease. Several antihypertensive treatment options are already available to counteract the progression of kidney disease. Despite the implementation of the clinical use of renin-angiotensin aldosterone system (RAAS) inhibitors, gliflozins, endothelin receptor antagonists, and their combination, the kidney damage associated with AH is far from being resolved. Fortunately, recent studies on the molecular mechanisms of AH-induced kidney damage have identified novel potential therapeutic targets. Several pathophysiologic pathways have been shown to play a key role in AH-induced kidney damage, including inappropriate tissue activation of the RAAS and immunity system, leading to oxidative stress and inflammation. Moreover, the intracellular effects of increased uric acid and cell phenotype transition showed their link with changes in kidney structure in the early phase of AH. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for hypertensive nephropathy management in the future. In this review, we would like to focus on the interactions of pathways linking the molecular consequences of AH to kidney damage, suggesting how old and new therapies could aim to protect the kidney.

Effects of non-contact electric fields on kidney and liver histology in tumour-induced rats

Background: A novel modality of cancer treatment based on exposure to non-contact electric fields has been developed to reduce the cancer incidence. However, the safety of this electric field exposure on vital organs has not been fully investigated. Therefore, the purpose of this study was to observe the safety of the electric field exposure on kidney and liver structures. Methods: Female Sprague-Dawley rats were divided into one control group and three treatment groups. Animals were treated with 7,12-dimethylbenz[a]anthracene for mammary tumour induction and exposed to non-contact electric fields individually for 10 hours a day for three weeks. Fresh samples of kidney and liver were collected for observation of structural damage in both organs. Both organs were prepared for histopathological cross-sectioning using the paraffin method and Hematoxylin &amp; Eosin staining followed by histological scoring using the post-examination masking method. Results: Damages found in the kidney were as follows: thickening of Bowman capsule, karyolysis, karyorrexhis, pyknosis, cloudy swelling, epithelial sloughing, inflammation, haemorrhage, and congestion. The thickening of Bowman’s capsule was significant, but other damages to the rest of kidney tissue were not significant. In addition, the number of inflammations and haemorrhages in the kidney structure of the placebo group was the lowest and significantly different compared to the other three groups. All damages to the kidneys were also found in the liver, but each showed a different degree of damage. The damages to the liver caused by exposure to the electric fields were not significant. Conclusions: Together with the effects of DMBA administration, exposure to non-contact electric fields can cause thickening of Bowman's capsule in the glomerulus of the kidney, however, in other kidney tissues and in the liver, exposure to this electric field was safe. It can even decrease the number of inflammations and haemorrhages in the organs.

Magnetic Resonance Imaging to Evaluate Kidney Structure, Function, and Pathology: Moving Toward Clinical Application

Recent advances in multiparametric Magnetic Resonance Imaging (MRI) allow multiple quantitative measures to assess kidney morphology, tissue microstructure, oxygenation, kidney blood flow and perfusion to be collected in a single scan session. Animal and clinical studies have investigated the relationship between the different MRI measures and biological processes, although their interpretation can be complex due to variations in study design and generally small participant numbers. However, emerging themes include the apparent diffusion coefficient (ADC) derived from diffusion weighted imaging, T1 and T2 mapping parameters and cortical perfusion being consistently associated with kidney damage and predicting kidney function decline. Blood Oxygen Level-Dependent (BOLD) MRI has shown inconsistent associations with kidney damage markers but has been predictive of kidney function decline in several studies. Therefore, multiparametric MRI of the kidneys has the potential to address the limitations of existing diagnostic methods to provide a non-invasive, non-contrast and radiation-free method to assess whole kidney structure and function. Barriers to be overcome to facilitate widespread clinical application include improved understanding of biological factors that impact MRI measures, development of a larger evidence base for clinical utility, standardization of MRI protocols, automation of data analysis, determining optimal combination of MRI measures, and health economic evaluation.

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5mL/kg/day for 10days); group B (REM) received REM (17mg/kg/day on the first day, and 8.5mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17mg/kg/day on the first day, and 8.5mg/kg/day on the 2nd-10th days) and DEX (7mg/kg/day, for 10days); group D (DEX) received DEX (7mg/kg/day for 10days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.

Evaluation of Launaea Angustifolia Extract Treatment on Rat Blood Serum Enzymes and Histology of Liver and Kidney

Background: Launaea angustifolia (LAN) is a wild plant grown in several Arabian countries in West Asia and North Africa. Launaea is a polymorphic inter- and intraspecific genus that includes about 54 species and 10 subspecies and is classified into eight sections. This study illustrates the effects of Launaea angustifo LAN (LAn) extract on male and female body weight and blood serum enzymes alanine aminotransferase (LAT) and Alkaline phosphatase LAN, with the histology of liver and kidneys used as an animal model for humans. Methods: A quantity of 100 mg of the extract powder was dissolved in 1 L of DMSO. Experimental rats were divided into five groups with 10 in each group (A, B, C, D, E: 100, 50 and 10 mg/kg and positive control and negative control, respectively). Result: No significant differences were observed between the treated and control-group females. However, the mean male body weight showed some variation within the 5th group (E) given the negative control (DMSO) and all treated groups presented lower body weights than the normal control (C). Analysis of the enzymatic activities of (ALT) alanine aminotransferase showed that the females in treatment group A (100 mg) and B (50 mg) had higher levels of ALT than those of group D females (10 mg) at P less than 0.05 and females in group E at P less than 0.001). The histology section of the liver and kidney and the histological structure of the rat kidney also showed no differences in all groups. Launaea angustifolia extract (LAn) was found to be safe, especially in the histology of the liver and kidney and for ALT and ALP blood parameters.

Up-regulation of the kidney renin angiotensin system contributes to long-term renal dysfunction in severe food restricted-refed female rats

Background: Severe food restriction (sFR) due to various psychological, environmental, and economical reasons can have adverse consequences to cardiovascular functioning and health. Less understood are the long-term risks for developing cardiovascular disease after the sFR period has ended. The renin-angiotensin system (RAS) is responsible for regulating blood pressure and we have found that the RAS is chronically upregulated months after the sFR is over and body weight (BW) recovered due to refeeding (sFR-Refed). AIM: Determine the role of the kidney in the chronic up-regulation of the RAS in sFR-Refed rats. Methods: We investigated the long-term consequences of sFR after refeeding on kidney structure and function in sFR-Refed rats. Female Fischer rats (3-months-old) were maintained on normal chow (Ctrl) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received regular chow ad libitum for 3 months. Kidney function was analyzed by precision ultrasound. ACE expression (qPCR) and activity (fluorescent assay) were measured and renal pathology was assessed by H&amp;E staining. Results: After 2 weeks of sFR, rats lost 15% of their initial BW [DFinal/Initial): Ctrl, 1.50±0.80 vs sFR, -15.4±1.1; p&lt;0.001; n=8]. After 3 months of refeeding, there was no detectable difference in BW, blood pressure and heart rate between Ctrl and sFR-Refed groups. However, the renal artery blood flow was reduced by 13% [(mm/s): Ctrl, 255 ± 12 vs sFR-Refed, 199 ± 7.8; p&lt;0.02; n=4-8 Glomeruli size was reduced [(mm): Ctrl, 399 ± 6.2 vs sFR-Refed, 383 ± 3.8; p&lt;0.05; n=9] and renal AT1R mRNA expression was increased by 1.3-fold [(fold of Ctrl): Ctrl, 1.00 ± 0.060 vs sFR-Refed, 1.29 ± 0.040; p&lt;0.005; n=8]. Conclusion: In summary, AT1Rs in the renal cortex are up-regulated under conditions in which kidney structure and function are impaired months after the sFR period has ended and BW is restored to normal levels. These findings suggest increased renal AT1R activity contributes to the long-term renal dysfunction observed in sFR-Refed rats. Further research is needed to understand how women who are subjected either voluntarily (e.g., crash diets) or involuntarily (e.g., very low food security) to periods of inadequate caloric intake could be at increased risk for developing renal disease later in life. AHA: 940246 (AS); IH 1R01HL119380 (KS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Intestinal mucosal flora of the intestine-kidney remediation process of diarrhea with deficiency kidney-yang syndrome in Sishen Pill treatment: Association with interactions between Lactobacillus johnsonii, Ca2+-Mg2+-ATP-ase, and Na+-K+-ATP-ase

This study aims to investigate the effect of Sishen Pill on the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Fifteen Kunming male mice were randomly divided into Normal control group (C), Model self-healing group (X) and Sishen Pill group (S), with 5 mice/cages. Hematoxylin eosin (HE) staining was used to observe the kidney structure. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA), Analysis of intestinal mucosal flora using third-generation high-throughput sequencing. The relative abundance results in the three groups revealed that the dominant bacterial genera: Lactobacillus, Muribaculum and Candidatus-Arthromitus; bacterial species: Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus murinus, and Lactobacillus intestinalis, and differences in the presence of major microbiota between the X and S groups. A positive correlation between Lactobacillus johnsonii and both Ca2+-Mg2+-ATP-ase and Na+-K+-ATP-ase was found via correlation analysis. Sishen Pill also changed the manufacture of other secondary metabolites, as well as the metabolism of carbohydrates, glycans, energy, lipids, and other amino acids, and xenobiotics biodegradation and metabolism. In conclusion, Sishen Pill improved kidney structure, energy metabolism and the diversity and structure of intestinal mucosal flora. In addition, Lactobacillus johnsonii may be a characteristic species of Sishen Pill in treating diarrhea with kidney-yang deficiency syndrome.

Chronic Kidney Disease among COVID-19 Patients Admitted in the Department of Medicine of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Comorbidities are frequently seen in admitted COVID-19 patients most common being hypertension, diabetes, cardiovascular diseases and chronic kidney disease. Chronic kidney disease is a slowly progressive chronic illness due to the gradual loss of kidney function or structure. The available data regarding the prevalence of chronic kidney disease and COVID-19 comorbidities is still limited. The aim of this study was to find out the prevalence of chronic kidney disease among COVID-19 patients admitted to the Department of Medicine of a tertiary care centre. A descriptive cross-sectional study was done in the Department of Medicine of a tertiary care centre. Data of medical records between 1 August 2020 to 1 December 2022 were reviewed retrospectively. The data was collected from 20 January 2023 to 20 March 2023. Ethical approval was obtained from the Institutional Review Committee (Reference number: 646/2079/80). Data on chronic kidney disease patients among COVID-19 patients were collected from the hospital records. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Among 584 COVID-19 patients admitted, the prevalence of chronic kidney disease was 43 (7.36%) (5.24-9.48, 95% Confidence Interval). A total of 30 (69.77%) were male and 13 (30.23%) were female with a mean age of 55±16.22 years. The prevalence of chronic kidney disease among COVID-19 patients admitted in the department of Medicine of a tertiary care centre was found to be slightly higher than other studies done in similar settings. chronic kidney disease; COVID-19; prevalence; tertiary care centre.

Hederagenin ameliorates renal fibrosis in chronic kidney disease through blocking ISG15 regulated JAK/STAT signaling.

Interstitial fibrosis is the key pathological characteristics of chronic kidney diseases (CKD). In this study, we reported that hederagenin (HDG) can effectively improve the renal interstitial fibrosis and its mechanism. We constructed CKD animal models of ischemia reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) respectively to observe the improvement effect of HDG on CKD. The results showed that HDG can effectively improve the pathological structure of kidney and the renal fibrosis in CKD mice. Meanwhile, HDG can also significantly reduce the expression of α-SMA and FN induced by TGF-β in Transformed C3H Mouse Kidney-1 (TCMK1) cells. Mechanistically, we performed transcriptome sequencing on UUO kidneys treated with HDG. By real time PCR screening of the sequencing results, we determined that ISG15 plays an important role in the intervention of HDG in CKD. Subsequently, we knocked-down ISG15 in TCMK1 and found that ISG15 knock-down significantly inhibited TGF-β-induced fibrotic protein expression and JAK/STAT activation. Finally, we performed electrotransfection and used liposomes to transfect ISG15 overexpression plasmids to up-regulate ISG15 in kidney and cells, respectively. We found that ISG15 can aggravate renal tubular cell fibrosis and abolish the protection of HDG on CKD. These results indicated that HDG significantly improves renal fibrosis in CKD by inhibiting ISG15 and its downstream JAK/STAT signaling pathway, which provides a new drug and research target for the subsequent treatment of CKD.

Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney.

Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRμCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRμCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRμCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals.

Structural and physiological changes of the kidney with age and its impact on chronic conditions and COVID-19

The kidney is an essential organ that removes waste products, balances the body's fluids, releases hormones that regulate blood pressure, produces an active form of vitamin D, promotes healthy bones, and controls the production of red blood cells. Structural and functional abnormalities occur in kidney with age. Alterations in kidney structure are based on physiological functions and environmental pressures. Variations in its structure across vertebrates are primarily due to the nature of alterations in number, complexity, arrangement, and location of the kidney tubules. Globally, individuals aged 65 and older are part of the fastest expanding population demographic, and as a result, a greater number of older patients are receiving a diagnosis of impaired renal function. The purpose of our mini-review is to summarize recent findings of the structural and functional differences between the normal and aging kidney, examine the evolutionary biology of the kidney across species, and demonstrate the role of aging in conditions such as diabetes, chronic kidney disease, and hypertension, along with their impact on SARS-CoV-2. Additional aims include discussing the potential therapeutic strategies to treat aged individuals with kidney health issues and how the impact of a healthy lifestyle, diet, and exercise can improve health conditions with aged kidneys.

Kidney Structure of Pangasianodon hypophthalmus Fed with Fermented Red Ginger and Infection by Aeromonas hydrophila

Red ginger contain antioxidant that can be used to enhance the immune system of fish. A study was conducted from September to December 2021 to understand the kidney structure of Pangasianodon hypophthalmus that fed with red ginger fermented pellets. The fermented red ginger juice was obtained by juicing 500 g of red ginger in 3L water, boiled and mixed with 175 ml molasses, 65 ml yogurt and 50 mg yeast and then was fermented for seven days. The fermented red ginger juice was obtained by juicing 500 g of red ginger in days. The fermented red ginger juice was mixed with fish feed pellets, namely T1 (150 mL/Kg), T2 (175 mL/Kg), T3 (200 mL/Kg), Cn (no red ginger juice and no infection), Cp (no red ginger juice and infection by A. hydrophila). The fish were reared in 30L aquaria. Fish sample was P. hypophthalmus fingerling (10-12 cm and 5-7 g), 10 fishes/aquarium. The fish were fed 3 time a day, adlibitum. In the 30th day, A. hydrophila was injected to the treated fish (0.1.ml of 108 cells/ml, subcutan injection). In the 14th after the infection kidney sample was collected and processed for histological study. Result shown that there were differences in kidney tissue of fish in each treatment. The worst condition was obtain in Cp, while the best was in T2. The renal structure of Cp showed abnormalities such as hemorrhage, cell necrosis, enlarged Bowman's cyst, and tubular degeneration, while the T2 kidney showed mild lesions specifically haemorrhagic. This fact indicates that fermented red ginger can improve fish immunity against A. hydrophila infection

Baseline and oxidatively damaged DNA in end-stage renal disease patients on varied hemodialysis regimens: a comet assay assessment.

Global estimates exhibit that one million people have end-stage renal disease, a disease-state characterized by irreversible loss of kidney structure and function, thus necessitating renal replacement therapy. The disease-state, oxidative stress, inflammatory responses, as well as the treatment procedure can have damaging effects on the genetic material. Therefore, the present study was carried out to investigate DNA damage (basal and oxidative) using the comet assay in peripheral blood leukocytes of patients (n = 200) with stage V Chronic Kidney Disease (on dialysis and those recommended but yet to initiate dialysis) and compare it to that in controls (n = 210). Basal DNA damage was significantly elevated (1.13x, p ≤ 0.001) in patients (46.23 ± 0.58% DNA in tail) compared to controls (40.85 ± 0.61% DNA in tail). Oxidative DNA damage was also significantly (p ≤ 0.001) higher in patients (9.18 ± 0.49 vs. 2.59 ± 0.19% tail DNA) compared to controls. Twice-a-week dialysis regimen patients had significantly elevated % tail DNA and Damage Index compared to the non-dialyzed and to the once-a-week dialysis group implying dialysis- induced mechanical stress and blood-dialyzer membrane interactions as probable contributors to elevated DNA damage. The present study with a statistically significant power implies higher disease-associated as well as maintenance therapy (hemodialysis)-induced basal and oxidatively damaged DNA, which if not repaired has the potential to initiate carcinogenesis. These findings mark the need for improvement and development of interventional therapies for delaying disease progression and associated co-morbidities so as to improve life expectancy of patients with kidney disease.