Renal Function Damage Research Articles

T-2 Toxin Nephrotoxicity: Toxic Effects, Mechanisms, Mitigations, and Future Perspectives.

T-2 toxin is a highly toxic fungal toxin that threatens humans and animals' health. As a major detoxifying and metabolic organ, the kidney is also a target of T-2 toxin. This article reviews T-2 toxin nephrotoxicity research progress, covering renal structure and function damage, nephrotoxicity mechanisms, and detoxification methods to future research directions. T-2 toxin damages kidney structure, causing renal dysfunction. The nephrotoxicity mechanism of T-2 toxin involves multiple factors including oxidative stress, endoplasmic reticulum stress, mitophagy, inflammatory responses, and apoptosis, which are intertwined and interdependent. Current detoxification strategies mainly involve reducing T-2 toxin in feedstuff and using antioxidant substances, but both have limits. Future research should focus on renal cells sensitivity to T-2 toxin, exploring key molecules in T-2 toxin's nephrotoxicity, renal injury's impact on other organs, and better detoxification methods. This review aims to guide future research and underpin T-2 toxin-induced nephrotoxicity prevention and treatment.

Effectiveness of a Novel PLA2R1 Knock-In Rat Model in Repairing Renal Function Damage.

Phospholipase A2 receptor 1 (PLA2R1) exists in many animals and plays an important role in membranous nephropathy. In this study, we aimed to evaluate a PLA2R1 knock-in rat model with repaired kidney function to study the molecular mechanisms of membranous nephropathy. We constructed the PLA2R1 knockout [PLA2R1(-)] model and PLA2R1 knock in [PLA2R1(+)] model in rats. Consistent complement C3 and IgA expression was confirmed through colocalization studies. Urinary biochemical indicators were performed using Automatic Biochemistry Analyzer. The complement C3, IgG, and Nephrin were detected by immunofluorescence assay. The expression levels of complement C3, IgA, and PLA2R1 were detected by western blot. The differential expression proteins (DEPs) between control and PLA2R1(+) models were detected by liquid chromatography with tandem mass spectrometry. The PLA2R1(-) model showed proteinuria, complement C3 aggregation, and IgA and IgG deposition in the glomerulus. Comparing with the PLA2R1(-) model, the PLA2R1(+) model, the deposition of complement C3 and IgA in the glomerulus did not completely disappear, and IgG expression weakened. Moreover, the absolute value of urinary protein was much lower in the PLA2R1(+) model than in the PLA2R1(-) model, and some of the humanized PLA2R1 gene fragments repaired some of the kidney functions. Humanized PLA2R1-insertion in rats can repair part of the renal function and reduce proteinuria, which will help in studying the molecular mechanisms of membranous nephropathy, as well as the entire membranous nephropathy-related system and complement activation signaling pathway.

Astragaloside IV attenuates podocyte apoptosis via regulating TXNIP/NLRP3/GSDMD signaling pathway in diabetic nephropathy

ObjectivesAmong all the diabetes complications brought on by persistent inflammation is diabetic kidney disease (DKD). One essential method of the inflammatory response's programmed cell death is anthrax. One of the main causes of diabetic renal disease progression in a high-glycemic environment is the lysis of renal resident cells.MethodThis investigation sought to determine whether Astragaloside IV (AS-IV)'s anti-pyroptosis action provides a protective function for the kidneys. For 12 weeks, db/db mice received 40 mg/kg of AS-IV by transgastric gavage. To validate the possible in vitro mechanism, mouse podocytes were cultivated for additional experiments.ResultsIn vitro, AS-IV led to a significant reduction in blood urea nitrogen (BUN), urine albumen-to-creatinine ratio (UACR), serum creatinine (CREA), and hyperglycemia in db/db mice and lessen the pathological alterations in the kidney. Moreover, pyrin structural domain of the NLR family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, gasdermin D (GSDMD), IL-18, and IL-1β were down-expressed and podocyte markers podocin and nphs1 were up-regulated following AS-IV intervention. By silencing GSDMD, we demonstrated in vitro that HG-stimulated podocytes undergo pyroptosis. We also discovered that AS-IV can mitigate this pyroptosis. To confirm that AS-IV prevented the NLRP3 inflammasome from activating, the NLRP3 inhibitor CY-09 was employed. It was also discovered that AS-IV prevents the expression of TXNIP and NLRP3 as well as their interaction. GSDMD expression was significantly downregulated following TXNIP-siRNA treatment, whereas GSDMD expression was upregulated in TXNIP overexpression cells; this upregulation could be undone with AS-IV.ConclusionsThe anti-pyroptosis effect of AS-IV via the TXNIP-NLRP3-GSDMD axis improves the renal function and podocyte damage of db/db mice and delays the onset of DKD, according to in vivo and in vitro experimental data.

Comparative Study of Safety and Efficacy of α-n-Butyl-2-cyanoacrylate Glue versus Traditional Embolization Materials in the Treatment of Acute Renal Hemorrhage.

Aims/Background This study aims to evaluate the safety and efficacy of α-n-butyl-2-cyanoacrylate (NBCA) glue in comparison with traditional embolization materials for the treatment of acute renal hemorrhage. Methods A total of 105 patients with the acute renal hemorrhage who underwent superselective renal artery embolization were enrolled. The patients were divided into two groups based on the embolization materials used: the traditional group (43 cases, control group) and the medical glue group (62 cases, observation group). Demographic characteristics, medical history, preoperative and postoperative 24-hour blood counts, renal function, and other clinical data were collected. The safety and efficacy of the two treatment methods were then compared between the groups. Results No significant difference in efficacy was observed between the traditional group and the medical glue group (p > 0.05). However, significant differences were found between the two groups in terms of embolization vessel grade, systemic immune-inflammation index (SII) difference, estimated glomerular filtration rate (eGFR) difference, and combined eGFR difference (p < 0.05). The traditional group exhibited a higher postoperative inflammatory response and greater renal function damage compared to the medical glue group. The degree of vascular embolization also influenced the extent of postoperative inflammatory response and renal function damage in patients with acute renal hemorrhage. Conclusion Compared to traditional embolization materials, NBCA glue demonstrates a clear hemostatic effect in the treatment of patients with acute renal hemorrhage, while also leading to reduced postoperative inflammatory response and renal function damage. NBCA adhesive is both safe and effective for treating acute renal hemorrhage.

Nephrotoxicity in locally advanced head and neck cancer: when the end justifies the means to preserve nutritional status during chemoradiation.

Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100mg/m2 given once every 3weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer. The treatment dramatically influenced every clinical and laboratory parameter, especially regarding nutritional status despite a high protein intake. In terms of medium eGFR decay, chemoradiotherapy reduced the renal function of about 8ml/min/1.73m2 in 6weeks, harboring some cases of mild acute kidney injury and acute kidney disease. Furthermore, patients with eGFR < 60mL/min/1.73m2 pre-treatment were just 3 (5%), becoming 5 (8.3%) at the end despite the high-protein diet implemented following ESPEN guidelines. The drop in eGFR did not correlate with weight loss during treatment or with anthropometric parameters pre and post. Nutritional counselling pre-, during, post-treatments plays a crucial role in preventing malnutrition and sarcopenia, leading to better oncological and nephrological outcomes too.

Effectiveness of a Novel PLA2R1 Knock-in Middle Age Rat Model in Repairing Renal Function Damage.

Phospholipase A2 receptor 1 (PLA2R1) exists important role in membranous nephropathy. In this study, we evaluate a PLA2R1 in a middle-aged rat model of renal function repair to further investigate the molecular mechanisms of membranous nephropathy. We analyzed the PLA2R1 knockout (KO) model and PLA2R1 knock in (KI) model in rats, extending the time to 85 weeks of age. Urinary biochemical indicators were detected using a fully automated biochemical analyzer. The complement C3, IgG, and Nephrin were detected using the immunofluorescence method. Western blot was used to detect the expression levels of complement C3, IgA and PLA2R1 in middle-aged models. The KO model continues to display glomerular proteinuria, complement C3 aggregation, and IgA and IgG deposition. Comparing with the KO model, the deposition of complement C3 and IgA in the glomerulus of the KI chimeric model still exists and IgG expression weakened. Inserting humanized PLA2R1 into rats can continuously repair partial renal function and reduce proteinuria, which will help investigate the pathogenesis of membranous nephropathy and complement activation signaling pathways.

Mincle Maintains M1 Polarization of Macrophages and Contributes to Renal Aging Through the Syk/NF-κB Pathway.

Kidney is a classic organ undergoing senescence, and chronic inflammation has an important effect in cellular senescence. Mincle has been shown to be vital for maintaining the M1 phenotype of macrophages, but its role in regulating renal aging has yet to be explored. Young (2 months of age) and old (24 months of age) mice were used to analyze the changes of kidney damage during natural aging. Mice were subcutaneously injected with D-galactose (D-gal) to establish a renal aging model, and miR-6948-3p mimic and Mincle siRNA were administered via the tail vein every 3 days. Aged kidney and experimental aging kidney were characterized by decreased renal function and structural damage, and upregulated expression of senescence-related proteins and SPAP components. The ratio of M1 macrophages was increased in the aged kidney, and Mincle accumulated in the aged kidney macrophages. Administration of miR-6948-3p mimic or Mincle siRNA alleviated D-gal-induced renal senescence. LPS was used to induce M1 polarization of bone marrow-derived macrophages, and a coculture system of M1 macrophages and mouse renal tubular epithelial cells (TCMK-1) was established. Mincle was upregulated in LPS-induced M1 macrophages in vitro, and silencing Mincle in M1 macrophages attenuated M1 macrophage-induced TCMK-1 cell senescence. Mechanistically, Mincle was regulated by miR-6948-3p and maintained the M1 phenotype of macrophages through the Syk/NF-κB pathway. In conclusion, Mincle, posttranscriptionally suppressed by miR-6948-3p, modulated renal senescence by maintaining the phenotype of M1 macrophages through the Syk/NF-κB pathway.

TLR4 Inhibitor TAK-242 Protected Henoch-Schonlein Purpura Nephritis in Rats by Regulating Inflammatory Response and Immune Competence via NF- κB/NLRP3 Signalling.

This study aimed to explore the effect of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signalling on Henoch-Schonlein purpura nephritis (HSPN). We established a HSPN rat model in a high-altitude hypoxic (HH) environment. Renal tissue lesions were observed by haematoxylin and Eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL), CD20-postive B cells and CD68-postive macrophage cells were detected by immunohistochemistry, T-cell activation was detected by flow cytometry and toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signalling was detected by western blot. TAK-242 inhibited the expression of TLR4/NF-κB/NLRP3 signalling related-proteins, decreased the levels of 24 h urinary protein, serum creatinine, circular immune complex (CIC) and kidney immunoglobulin A (IgA), and improved renal histopathological damage in HH-HSPN rats. Furthermore, TAK-242 attenuated the infiltration of CD20 and CD68 into the kidney and increased the percentage of CD3+, CD4+ and CD4+/CD8+ cells in the blood of HH-HSPN rats. The study revealed that suppressing TLR4/NF-κB/NLRP3 signalling improved renal function and histopathological damage, and this improvement was related to inhibiting the inflammatory response and enhancing immune competence.

Intramuscular injection of Bothrops jararaca venom provoked acute kidney injury (AKI): Underpinned by impaired renal filtration, Na+ handling, and tissue damage

Globally, about 2.5 million people are victims of snakebites annually. In Brazil, the most clinically relevant snake is the Bothrops jararaca. The symptoms of envenomation are acute inflammation at the bite site and bleeding disorders. Despite kidney failure being the main cause of death after envenomation, kidney damage is not completely understood, and there are no clinically representative in vivo models. This work aimed to characterize the acute kidney injury (AKI) induced by intramuscular injection (IM) of Bothrops jararaca (Bjc) venom in male Wistar rats. The control group received 0.9% saline solution. Three doses of venom (3.5, 6.0, and 8.0 mg/kg) were administered IM into the posterior region of the right knee. After the injection, the rats were kept in metabolic cages. The following parameters were analyzed after 24 h: the extent of muscle damage and kidney damage (urinary creatinine, proteinuria, plasma creatinine, and renal tissue histology). All rats presented a hemorrhagic lesion at the injection site in a dose-dependent manner. Biochemical parameters indicated kidney damage: plasma creatinine accumulation, decreased glomerular filtration rate, albuminuria and proteinuria, and disturbance in Na+ homeostasis. Histological analyses showed glomerular injury, tissue discontinuity more evident in the cortex and tubular dilatation, and collagen deposition. The decline in renal function and tissue damage indicated the occurrence of AKI. Therefore, a Bjc venom-induced in vivo model of renal injury has been established for future studies.

Efficacy of atorvastatin on renal function in patients with contrast-induced nephropathy after percutaneous coronary intervention

BackgroundAt present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI).MethodsIn this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups.ResultsAfter surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P < 0.05). Meanwhile, the incidences of ARs during hospitalization between patients in the Exp and Ctrl groups were all 8%, showing no observable difference (P > 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization.ConclusionTaken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety.

Influence of preoperative HbA1c levels on the occurrence of postoperative complications in patients undergoing coronary artery bypass grafting.

To explore the impact of preoperative HbA1c levels on postoperative complications in coronary heart disease patients undergoing coronary artery bypass grafting (CABG). From September 2020 to November 2022, 98 patients with coronary heart disease who were preparing to receive CABG treatment in a cardiac surgery department of a certain hospital were included in the study using the retrospective analysis. According to the preoperative serum hemoglobin A1C (HbA1c) test results, patients were divided into a low-level group (HbA1c < 5.7%, 20 cases), a medium level group (HbA1c: 5.7% ~ 7.0%, 59 cases), and a high level group (> 7%, 19 cases). The surgical outcomes and postoperative complications among the three groups were compared. There was no statistically significant difference in the number of bypass grafts, mechanical ventilation time, and hospitalization time among the three groups of patients (P > 0.05). The high-level group stayed in the ICU longer than the other two groups, while the middle level group had a longer stay than the low-level group (P < 0.05). Within one year of postoperative follow-up, the occurrence of postoperative complications was 20.00%, 32.20%, and 47.37%, respectively, with no statistically significant difference (P > 0.05). Among them, the incidence of acute kidney injury in the high-level group was higher than that in the other groups (P < 0.05), but the correlation difference between the middle and low level groups is P > 0.05. The incidence of infection in the middle level group was higher than that in the low level group (P < 0.05), but the incidence of infection in the high and low level groups was P > 0.05 compared to the medium level group. For patients with coronary heart disease undergoing CABG, the higher the preoperative HbA1c level, the longer their postoperative stay in the ICU, and the higher the risk of acute renal function damage.

Cisplatin induces kidney damage through the down-regulation of Prx I by autophagic degradation

In this study, we investigated the potential role of PrxI in cis-diamminedichloroplatinum (cisplatin)-induced renal damage in mice. The anticancer drug cisplatin is a chemotherapeutic agent that is widely used to treat solid tumors. Cisplatin-induced nephrotoxicity is a serious dose-limiting side effect, primarily caused by oxidative stress. The oxidative stress further damages DNA, membranes, and mitochondria, and increases endoplasmic reticulum (ER) stress. Cisplatin produces reactive oxygen species (ROS) through Cytochrome P450 2E1 (CYP2E1) and localizes to the surface of the ER, where CYP2E1 is located.Among the six Prx isoforms, Prx I was selectively degraded in cisplatin-treated kidneys during severe renal function damage. Prx I degradation is blocked in mouse proximal tubular cells treated with 3-methyladenine, an autophagy inhibitor, and in MEF lacking ATG7. Moreover, increased ROS levels on the ER surface due to CYP2E1 overexpression further accelerated Prx I degradation. These results suggest that Prx I degradation is largely mediated through autophagy, which is promoted by cisplatin-induced ER stress. Ablation of Prx I exacerbated cisplatin-induced nephrotoxicity and significantly increased the abundance of oxidative stress, ER stress, and inflammatory markers in the kidney, indicating that Prx I plays a protective role against cisplatin-induced nephrotoxicity.

Correlation between Occupational Noise Exposure and Renal Dysfunction in Male Workers

Objective: This study aimed to explore the relationship between occupational noise exposure and renal dysfunction in male workers. Methods: A total of 160 male workers (the number of people who met the inclusion criteria) who underwent health examinations in Qingdao Municipal Hospital from January 2023 to December 2023 were grouped into a noise group (80 cases) and a control group (80 cases) based on whether they engaged in noise work. We compared the differences in creatinine (CREA), cystatin C (CysC) and blood urea nitrogen (BUN) levels between the two groups. We also compared the differences in the above renal function indicators among workers with different working years in the noise group, as well as observed the relationship between renal dysfunction and noise exposure. Results: The levels of BUN, CREA and CysC in the noise group were significantly higher than those in the control group (P &lt; 0.05). The overall abnormal rate of renal function in the noise group (42.50%) was significantly higher than that in the control group (11.25%, P &lt; 0.05). The levels of BUN, CREA and CysC all significantly increased with the increase in working years (P &lt; 0.05). The noise exposure intensity and cumulative noise exposure (CNE) of the group with renal dysfunction were higher than those of the group with normal renal function (P &lt; 0.05). The area under the curve was 0.811 (95% confidence interval: 0.714–0.908), the optimal cut-off value of CNE was 96.53 dB (A) · year, the sensitivity was 89.29%, the specificity was 83.32% and the Youden index was 72.61%. Conclusion: There may be a correlation between long-term noise exposure and renal function. The intensity of noise exposure and CNE may have a certain correlation with renal function damage in occupational noise-exposed workers.

Quantitative assessment of renal steatosis in patients with type 2 diabetes mellitus using the iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification sequence imaging: repeatability and clinical implications.

Fatty kidney disease is linked to renal function damage, but there is no noninvasive tool for monitoring renal fat accumulation. This study aimed to explore the repeatability of the iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification (IDEAL-IQ) sequence imaging in quantifying renal fat deposition and to assess the differences observed in patients with type 2 diabetes mellitus (T2DM). A total of 26 healthy participants underwent two IDEAL-IQ scans without repositioning, and the repeatability of the imaging technique was assessed with Bland-Altman analysis. Additionally, 96 patients with T2DM underwent a single IDEAL-IQ scan for the examination of renal fat deposition. The patients with T2DM were classified into three groups based on their estimated glomerular filtration rate (eGFR). One-way analysis of variance was used to analyze the differences of renal fat depositions between the groups. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of IDEAL-IQ. Bland-Altman analyses showed narrower limits of agreement and a significant correlation (r=0.81; P<0.05) between the two IDEAL-IQ scans. Statistically significant differences between the healthy volunteers and patients with T2DM, diabetic kidney disease (DKD) I-II, and or DKD III-IV were found in renal parenchymal proton-density fat fraction (PDFF) values (P<0.001). Renal parenchymal PDFF was negatively correlated with eGFR (r=-0.437; P<0.001) and positive correlated with serum creatinine level (µmol/L) (r=0.421; P<0.001). The area under the curve of IDEAL-IQ in discriminating between the healthy volunteers and patients with T2DM was 0.857. For discriminating T2DM from DKD I-II and DKD III-IV, the IDEAL-IQ had an area under the curve of 0.689 and 0.823, respectively. IDEAL-IQ is a promising and reproducible technique for the assessment of renal fat deposition and identification of risk of DKD in patients with T2DM. Moreover, IDEAL-IQ imaging is expected to improve the sensitivity and specificity of early renal function damage and staging assessment of patients with T2DM.

Preparation and biological evaluation of a glucose-responsive block copolymer nanoparticle with the ability to ameliorate diabetic kidney damage

In this study, a p(AAPBA-b-Daidzein) block copolymer was designed and synthesised using glucose-responsive 3-acrylamidophenylboronic acid (AAPBA) and esterified daidzein as structural units; this copolymer possessed anti-diabetic pharmacological activity. After confirming the chemical structure of the copolymer, nanoparticles of the copolymer were prepared using the water-in-oil method. The results of the in vitro experiments showed that nanoparticles swelled when the pH was >7 or when the glucose concentration exceeded 1.0 mg/mL. Particle size measurements showed that the size of the nanoparticles was kept in the range of 100–300 nm before and after the glucose response, which helped avoid their clearance by the liver and kidneys. As the nanoparticles swelled, insulin and esterified daidzein were continuously released. The nanoparticles subcutaneously injected into mice with streptozotocin-induced diabetes were able to quickly and continuously reduce the blood sugar levels; significantly improve renal pathological damage and reduce renal function damage, inflammatory factors and oxidative stress indicators. In summary, the p(AAPBA-b-Daidzein) glucose-responsive nanoparticles prepared in the current study possess good pH value and glucose sensitivity, can achieve a precise and controlled release of insulin and exert the pharmacological activity of esterified daidzein. Therefore, it shows potential clinical application value in the treatment of diabetes and its complications.

SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies

Context: Diabetic nephropathy is the leading cause of end-stage renal disease and also death in the world. Administration of Szeto-Schiller-31 (SS-31) as a potential therapeutic candidate that can decrease the renal function damage progressivity in diabetes needs to be comprehensively analyzed. Aims: To assess the protective effects of SS31 against the progressivity of diabetic nephropathy. Methods: This systematic review follows PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines 2020. Searches of databases (Pubmed, Science Direct, Scopus, ProQuest, and Springer) were done on 17 September 2023 in order to find articles related to the animal diabetic model and SS-31 treatment. Manual searches from medRxiv were also conducted to obtain additional evidence. Renal function, histopathology analysis, reactive oxygen species in vivo, and in vitro analysis were described. Results: There were six in vivo studies, each of which discussed the renal function, histopathology, and reactive oxygen species (ROS), and four in vitro studies that discussed ROS. The available data suggested that SS-31 improves kidney function by lowering urinary albumin excretion, proteinuria, serum creatinine, creatinine clearance, and BUN, supported by histopathological improvements. In addition, SS-31 also has the effect of lowering 8-hydroxy-2-deoxyguanosine (8-OHdG) level, malondialdehyde (MDA) level, and nicotinamide adenine dinucleotide phosphate (NADPH) expression. Conclusions: SS31 had a renoprotective effect that could prevent the worsening of renal function in diabetic mice. In addition, the results of histopathology and ROS analysis also support the positive results of SS-31 treatment. Further studies are required to confirm its findings.

Research on Experimental Hypertension in Prague (1966-2009).

The study of ontogenetic aspects of water and electrolyte metabolism performed in the Institute of Physiology (Czechoslovak Academy of Sciences) led to the research on the increased susceptibility of immature rats to salt-dependent forms of hypertension since 1966. Hemodynamic studies in developing rats paved the way to the evaluation of hemodynamic mechanisms during the development of genetic hypertension in SHR. A particular attention was focused on altered renal function and kidney damage in both salt and genetic hypertension with a special respect to renin-angiotensin system. Renal damage associated with hypertension progression was in the center of interest of several research groups in Prague. The alterations in ion transport, cell calcium handling and membrane structure as well as their relationship to abnormal lipid metabolism were studied in a close cooperation with laboratories in Munich, Glasgow, Montreal and Paris. The role of NO and oxidative stress in various forms of hypertension was a subject of a joint research with our Slovak colleagues focused mainly on NO-deficient hypertension elicited by chronic L-NAME administration. Finally, we adopted a method enabling us to evaluate the balance of vasoconstrictor and vasodilator mechanisms in BP maintenance. Using this method we demonstrated sympathetic hyperactivity and relative NO deficiency in rats with either salt-dependent or genetic hypertension. At the end of the first decennium of this century we were ready to modify our traditional approach towards modern trends in the research of experimental hypertension. Keywords: Salt-dependent hypertension o Genetic hypertension o Body fluids o Hemodynamics o Ion transport o Cell membrane structure and function o Renal function o Renin-angiotensin systems.

Evaluating iron replacement therapies in pediatric CKD: A comparative analysis of oral liposomal iron, iron supported lactoferrin and IV iron Dextran

CKD is defined as longstanding kidney damage and reduction in renal function. The global burden of CKD in the pediatric population is 15 per million, with congenital renal anomalies and hereditary disorders being the primary causes. Of these, 10% of patients require RRT. The development of anemia in chronic disease is a significant concern as the disease progresses. This condition exacerbates the pathological state by increasing the risk of infection, inevitably resulting in mortality. The study aims to establish the comparative analysis of three types of iron replacement therapies including oral liposomal iron, iron supported lactoferrin and IV iron dextran by evaluating their safety and efficacy corresponding to the different stages of CKD in pediatric population. A comparison between all three variants of iron replacement therapy shows oral liposomal iron provides higher bioavailability and tolerance but effective only in lower CKD stages. In IV iron dextran, rapid iron store replenishment has been observed, but with significant side effects, including the risk of severe hypersensitivity reaction. Conversely, oral iron-supported lactoferrin has demonstrated a maximal iron recovery response after six months of therapy, but with frequent gastrointestinal side effects.

Hyperechoic Spots in the Renal Medulla as a Potential Indicator of Early Gouty Nephropathy

Introduction: The aim of the study was to explore the causes and clinical significance of hyperechoic renal medulla observed by ultrasonography in patients with primary gout. Methods: This study included 2,107 patients with primary gout treated in the Gout Clinic of our hospital from 2016 to 2022. The clinical data and biochemical data of these patients were collected and analyzed. According to the presence or absence of punctate hyperechogenicity in the renal medulla on ultrasound examination, the patients were divided into the hyperechoic medulla (HM) and the normal hypoechoic medulla (NM) groups, and the HM group was further divided into the partial HM (P-HM) and fulfilled HM (F-HM) subgroups according to the distribution range of hyperechogenicity. Results: Among the 2,107 patients with primary gout, 380 had hyperechoic renal medulla on renal ultrasound, including 106 patients with F-HM and 274 with P-HM. There were significant differences in the gout duration, urate arthropathy number, serum urate (SU) level, clinical tophi number, blood urea nitrogen, serum creatinine (sCr), and estimated glomerular filtration rate between the HM and NM groups or between the F-HM and P-HM subgroups (p < 0.05). Multivariate regression analysis showed that the presence of HM was positively correlated with gout duration, urate arthropathy number, gout attack frequency, SU, and sCr. The number of clinical tophi and sCr were closely related to F-HM. Conclusion: Ultrasound examination showed that a high medulla echo in patients with gout was often related to renal function damage. P-HM may be a transitory condition between NM and F-HM in patients with gout.

Lycopene alleviates zearalenone-induced oxidative stress, apoptosis, and NLRP3 inflammasome activation in mice kidneys

The aim of this study was to investigate the protective effects of lycopene on renal damage caused by zearalenone (ZEN). Male Kunming mice were treated daily for 4 weeks by intragastric administration with 40 mg/kg ZEN in the presence or absence of lycopene (2.5 or 5 mg/kg). The results showed that lycopene markedly alleviated the damage of renal structure and function in mice induced by ZEN, as indicated by the reduced degree of pathological damage and the decreased levels of urea nitrogen and creatinine. Meanwhile, results of dihydroethidine (DHE) staining and biochemical markers revealed that ZEN exposure notably increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased the level of GSH, and reduced the activities of catalase (CAT) and superoxide dismutase (SOD). Administration of lycopene alleviated the increased oxidative stress induced by ZEN. Moreover, ZEN ingestion notably resulted in apoptosis, increased the protein levels of BCL2 associated X protein (Bax) and cleaved caspase-3, and decreased the protein levels of apoptosis regulator Bcl-2 (Bcl-2), which were reversed by lycopene intervention. Results of immunofluorescence demonstrated that lycopene reversed ZEN-induced the upregulation of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), Caspase-1, and interleukin-1 beta (IL-1β) in mice kidneys. Lycopene supplementation could alleviate ZEN-induced renal toxicity by inhibiting oxidative stress, apoptosis, and NLRP3 inflammasome activation.