Kidney Damage Research Articles

Towards equitable renal care: Strategies for enhancing kidney transplantation in Africa

Chronic kidney disease (CKD) is defined as the presence of kidney damage persisting for 3 months or more. Kidney transplantation stands as a vital intervention for individuals grappling with end-stage renal disease (ESRD) in Africa, offering the promise of extended life and improved quality of life. However, numerous challenges hinder its widespread implementation across the continent. This paper explored kidney transplantation in Africa, aiming to illuminate key strategies for bridging gaps and building pathways to enhanced renal care. There is a disproportionate burden of CKD on the region's population. Therefore, there is a critical need for early diagnosis and intervention. This paper outlines comprehensive strategies for improving kidney transplantation in Africa. Results indicate that financial support systems, infrastructure enhancement, public awareness campaigns, and legal frameworks are essential for addressing renal care barriers. Active measures such as government subsidy programs, international funding collaboration, and engagement with community leaders are highlighted as effective approaches. Drawing from global standards and best practices, the paper shows the importance of tailored approaches that address Africa's unique socio-economic and healthcare landscape. By leveraging collaborative efforts, regulatory frameworks, and public engagement, African nations can overcome barriers to kidney transplantation and pave the way for equitable access to life-saving treatment.

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury.

Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

In Vitro and In Vivo Antiurolithic Effect of Betulinic Acid Obtained from Citharexylum mirianthum.

The study aimed to investigate the potential antiurolithic effects of extracts, fractions, and betulinic acid (BA) from Citharexylum mirianthum. In vitro analysis involved precipitating calcium oxalate (CaOx) crystals in urine. For in vivo studies, rats were divided into four groups: naive; vehicle; potassium citrate (KC); and BA. Urolithiasis was induced using ethylene glycol and ammonium chloride. After seven days, urine, blood, and kidney tissues were evaluated. The results showed that methanolic extract, hexane, dichloromethane, and ethyl acetate fractions, as well as BA, reduced CaOx crystal formation. In vivo, the vehicle-treated group exhibited reduced urinary volume and Na+ excretion, while the BA-treated group showed restored urinary volume and Na+ excretion similar to the naive group. BA also significantly reduced urinary monohydrate and dihydrate crystal formation, comparable to the KC group. Other urinary parameters remained unchanged, but plasma analysis revealed decreased Na+, K+, and Ca2+ in the KC group. Renal tissue analysis indicated reduced lipid hydroperoxides and increased reduced glutathione in all urolithiasis groups, with unchanged nitrite levels. BA treatment also improved renal corpuscle morphology. Overall, our findings demonstrate that treatment with BA effectively prevented kidney damage induced by EG+AC ingestion, thereby improving renal function in the urolithiasis model.

Chronic infusion of the tryptophan metabolite kynurenine increases mean arterial pressure in male Sprague-Dawley rats.

Chronic kidney disease is the loss of renal function that can occur from aging or through a myriad of other disease states. Rising serum concentrations of kynurenine, a tryptophan metabolite, have been shown to correlate with increasing severity of chronic kidney disease. This study used chronic intravenous infusion in conscious male Sprague-Dawley rats to test the hypothesis that kynurenine can induce renal damage and promote alterations in blood pressure, heart rate, and decreased renal function. We found that kynurenine infusion increased mean arterial pressure, increased the maximum and minimum range of heart rate, decreased glomerular filtration rate, and induced kidney damage in a dose-dependent manner. This study shows that kynurenine infusion can promote kidney disease in healthy, young rats, implying that the increase in kynurenine levels associated with chronic kidney disease may establish a feed-forward mechanism that exacerbates the loss of renal function.NEW & NOTEWORTHY In humans, an elevated serum concentration of kynurenine has long been associated with negative outcomes in various disease states as well as in aging. However, it has been unknown whether these increased kynurenine levels are mediating the disorders or simply associated with them. This study shows that chronically infusing kynurenine can contribute to the development of hypertension and kidney impairment. The mechanism of this action remains to be determined in future studies.

Chronic Kidney Disease-associated Lung Injury Is Mediated by Phosphate-induced MAPK/AKT Signaling.

Chronic kidney disease (CKD) is associated with systemic phosphate elevations, called hyperphosphatemia. Translational studies have shown that hyperphosphatemia contributes to CKD-associated inflammation and injury in various tissues, including the kidney, heart, liver, and parathyroid gland. Mechanisms underlying pathologic actions of elevated phosphate on cells are not well understood but seem to involve uptake of phosphate through sodium-phosphate cotransporters and phosphate-induced signaling via fibroblast growth factor receptor (FGFR) 1. Clinical studies indicate CKD patients are more likely to develop inflammatory and restrictive lung diseases, such as fibrotic interstitial lung diseases, and here we aimed to determine whether hyperphosphatemia can cause lung injury. We found that a mouse model of CKD and hyperphosphatemia, induced by an adenine-rich diet, develops lung fibrosis and inflammation. Elevation of systemic phosphate levels by administration of a high-phosphate diet in a mouse model of primary lung inflammation and fibrosis, induced by bleomycin, exacerbated lung injury in the absence of kidney damage. Our in vitro studies identified increases of proinflammatory cytokines in human lung fibroblasts exposed to phosphate elevations. Phosphate activated extracellular signal related kinase (ERK) 1/2 and protein kinase B (PKB/AKT) signaling, and pharmacological inhibition of ERK, AKT, FGFR1, or sodium-phosphate cotransporters prevented phosphate-induced proinflammatory cytokine upregulation. Additionally, inhibition of FGFR1 or sodium-phosphate cotransporters decreased the phosphate-induced activation of ERK and AKT. Our study suggests that phosphate can directly target lung fibroblasts and induce an inflammatory response and that hyperphosphatemia in CKD and non-CKD models contributes to lung injury. Phosphate-lowering strategies might protect from CKD-associated lung injury.

SENP1 reduces oxidative stress and apoptosis in renal ischaemia-reperfusion injury by deSUMOylation of HIF-1α.

Renal ischaemia-reperfusion injury (RIRI) is a primary cause of acute kidney damage, occurring frequently insituations like renal transplantation, yet the underlying mechanisms were not fully understood. Sentrin-specific protease 1 (SENP1) is an important member of the SENP family, which is widely involved in various diseases. However, the role of SENP1 in RIRI has been unclear. In our study, we discovered that SENP1 was involved in RIRI and reduced renal cell apoptosis and oxidative stress at elevated levels. Further mechanistic studies showed that hypoxia-inducible factor-1α (HIF-1α) was identified as a substrate of SENP1. Furthermore, SENP1 deSUMOylated HIF-1α, which reduced the degradation of HIF-1α, and exerted a renoprotective function. In addition, the protective function was lost after application of the HIF-1α specific inhibitor KC7F2. Briefly, our results fully demonstrated that SENP1 reduced the degradation of HIF-1α and attenuated oxidative stress and apoptosis in RIRI by regulating the deSUMOylation of HIF-1α, suggesting that SENP1 may serve as a potential therapeutic target for the treatment of RIRI.

Primary Care Considerations for the Adolescent Wrestler.

Adolescent wrestlers undergo intense physical combat. While guidelines are effective in keeping the sport safer, concerns specific to the adolescent wrestler may be missed at primary care visits without knowledge of the unique challenges faced by these athletes. The following review highlights important characteristics of the adolescent wrestler which are of interest to primary care providers. Recommendations for concussion management are evolving to gradual return-to-sport after physician clearance rather than total sport removal. Prolonged skin-to-skin contact also places athletes at greater risk of dermatologic infections, which often require removal from competition, treatment, and/or coverage. Finally, adolescent nutritional literature recommends limiting pre-match weight loss to 3-5% body weight due to noted kidney damage that may result from larger deficits. Adolescent wrestlers are more prone to acute injuries than chronic overuse injuries, with most injuries occurring above the trunk. Primary care providers should consider obtaining imaging to rule out severe injuries or referring to specialist providers. Current guidelines for skin infections require frequent pre-match skin checks and mandatory waiting periods when certain infections are identified. However, the primary care provider is well-equipped for more in-depth skin examination, discussion of skin hygiene, and appropriate treatment of skin infections. Athletes attempting to meet lower weight classes may put themselves at risk of acute kidney damage, under-fueling, and eating disorders. Current guidelines attempt to mitigate excessive weight changes in the adolescent wrestler during competition season, but primary care providers should emphasize healthier methods of weight fluctuation and look for indicators of physiological or psychological effects.

Can Apigenin Be an Effective Therapeutic Agent Against Experimental Renal Ischemia-Reperfusion Injury?

Aim: This study aims to reveal the effects of two doses of apigenin (API) against renal ischemia-reperfusion injury (R I/R). Material and Methods: For this purpose, 5 and 10 mg/kg doses of API were preferred in our study, and the groups were designed as sham, R I/R, 5 mg/kg API, and 10 mg/kg API groups for the implementation of the experimental protocol. In the R I/R model, 1-hour ischemia and 24-hour reperfusion periods were preferred. Oxidative and inflammatory markers were measured biochemically in samples taken at the end of the experiment. Results: Biochemical results showed that oxidative and inflammatory markers increased significantly in the R I/R group, but antioxidant activities decreased significantly. In the 5 and 10 mg/kg API groups, R I/R damage was alleviated considerably, with these markers approaching the sham group values. Conclusion: As a result, the study's results determined that two different doses of API were effective against R I/R-induced kidney damage.

Possibilities of Azilsartan Medoxomil for Preparation for Planned Percutaneous Coronary Intervention in Patients With Type 2 Diabetes Mellitus.

To evaluate the efficacy and safety of azilsartan medoxomil for preoperative preparation and improving the long-term prognosis of elective percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD), arterial hypertension (AH), and type 2 diabetes mellitus (DM). The study sample included patients with type 2 DM referred for elective PCI who had poor blood pressure (BP) control according to 24-hour BP monitoring (24-BPM) (mean daily systolic BP ≥130 mmHg, mean daily diastolic BP ≥80 mmHg). The data were collected from 2018 through 2020. A total of 75 patients was included and distributed by simple randomization into two groups: group 1 (main, n=37) received azilsartan medoxomil as an antihypertensive drug at a dose of 40 mg/day (previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARB) were discontinued); group 2 (control, n=38) continued on their previous antihypertensive therapy. The follow-up period was 6 months. During each of 5 consecutive follow-up visits, the patient was examined, 24-BPM was recorded, and urinary markers of renal dysfunction (glomerular filtration rate, GFR; neutrophil gelatinase-associated lipocalin, NGAL; urine albumin-creatinine ratio, UACR; kidney injury molecule, KIM-1; and interleukin-18, IL-18) were measured. During the azilsartan treatment, GFR decreased by 7.4%, while in the control group, it decreased by 18.9% (p<0.001). For 6 months of follow-up, no changes in the NGAL concentration were found in the main group, while the NGAL concentration in the control group increased by 12.9%. With azilsartan, there was a decrease in the urinary concentration of IL-18 (16.9%), while in patients of the control group, IL-18 increased (7.14%). Proteinuria progressed in both groups, which was expectable given the presence of DM; however, in patients receiving azilsartan, the UACR value increased by 37.5%, while in patients of the control group, it increased by 96.15%. These differences were statistically significant. No statistically significant differences were found in the concentrations of cystatin C and KIM-1. This study demonstrated two important facts: the possibility for diagnosing contrast-induced acute kidney injury (CI-AKI) using new, more sensitive markers of kidney damage, which is important for assessing the effectiveness of prevention, and the possibility of using ARBs, in particular azilsartan, for the prevention of CI-AKI in patients with IHD in combination with AH and DM.

Systemic Lupus Erythematosus: Causes, Symptoms and Treatment Options

Systemic lupus erythematosus is a chronic autoimmune disease where the body's immune system mistakenly attacks its own tissues and organs. Common symptoms include fatigue, joint pain and swelling, skin rashes (especially the butterfly rash on the face), fever, chest pain, and sensitivity to sunlight. Diagnosis typically involves a combination of medical history, physical examination, laboratory tests (such as blood tests for antibodies like ANA), and imaging studies. Treatment for systemic lupus erythematosus involves a combination of medications to control symptoms and minimize organ damage, alongside lifestyle changes like sun protection and exercise. SLE can lead to various complications, including kidney damage (lupus nephritis), cardiovascular problems, neurological disorders, osteoporosis, and increased susceptibility to infections.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats

BackgroundChronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH.MethodsThis study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile.ResultsAt 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group.ConclusionsOur findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.Graphical

Hypotensive and Cardioprotective Potential of Yellow Bedstraw Extract-Based Oral Liquid in Spontaneously Hypertensive Rats.

This study aimed to prepare, characterize and assess the antioxidant activity of yellow bedstraw extracts (YBEs), focusing on identifying extracts with high antioxidant capacity. The selected extract was loaded into an oral liquid formulation and further investigated for its therapeutic potential in reducing blood pressure and associated complications in spontaneously hypertensive Wistar kyoto rats (SHR). Rats were divided into untreated SHR and SHR treated with a YBE-based oral formulation over four weeks. After treatment, blood pressure was measured, and cardiac function was assessed using the Langendorff technique to simulate ex vivo ischemic conditions. Prooxidant levels were assessed in plasma while antioxidant activity was evaluated in red blood cells. Histological analyses of heart, kidney, and liver samples were conducted to assess pathological changes induced by hypertension. Our results showed that the oral formulation loaded with ethanol YBE effectively reduced blood pressure, preserved myocardial function under ischemic stress, and decreased oxidative stress markers in blood. Importantly, our formulation with YBE demonstrated potential in attenuating structural kidney damage associated with hypertension. Overall, these findings suggest a cardioprotective effect of orally administered YBE formulation, highlighting its potential as an herbal supplement. However, clinical studies are warranted to validate these findings and explore the extract's suitability for clinical use.

Prevalence and metabolic risk factors of chronic kidney disease among a Mexican adult population: a cross-sectional study in primary healthcare medical units.

The intricate relationship between obesity and chronic kidney disease (CKD) progression underscores a significant public health challenge. Obesity is strongly linked to the onset of several health conditions, including arterial hypertension (AHTN), metabolic syndrome, diabetes, dyslipidemia, and hyperuricemia. Understanding the connection between CKD and obesity is crucial for addressing their complex interplay in public health strategies. This research aimed to determine the prevalence of CKD in a population with high obesity rates and evaluate the associated metabolic risk factors. In this cross-sectional study conducted from January 2017 to December 2019 we included 3,901 participants of both sexes aged ≥20 years who were selected from primary healthcare medical units of the Mexican Social Security Institute (IMSS) in Michoacan, Mexico. We measured the participants' weight, height, systolic and diastolic blood pressure, glucose, creatinine, total cholesterol, triglycerides, HDL-c, LDL-c, and uric acid. We estimated the glomerular filtration rate using the Collaborative Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Among the population studied, 50.6% were women and 49.4% were men, with a mean age of 49 years (range: 23-90). The prevalence of CKD was 21.9%. Factors significantly associated with an increased risk of CKD included age ≥60 years (OR = 11.70, 95% CI [9.83-15.93]), overweight (OR = 4.19, 95% CI [2.88-6.11]), obesity (OR = 13.31, 95% CI [11.12-15.93]), abdominal obesity (OR = 9.25, 95% CI [7.13-11.99]), AHTN (OR = 20.63, 95% CI [17.02-25.02]), impaired fasting glucose (IFG) (OR = 2.73, 95% CI [2.31-3.23]), type 2 diabetes (T2D) (OR = 14.30, 95% CI [11.14-18.37]), total cholesterol (TC) ≥200 mg/dL (OR = 6.04, 95% CI [5.11-7.14]), triglycerides (TG) ≥150 mg/dL (OR = 5.63, 95% CI 4.76-6.66), HDL-c <40 mg/dL (OR = 4.458, 95% CI [3.74-5.31]), LDL-c ≥130 mg/dL (OR = 6.06, 95% CI [5.12-7.18]), and serum uric acid levels ≥6 mg/dL in women and ≥7 mg/dL in men (OR = 8.18, 95% CI [6.92-9.68]), (p<0.0001). These factors independently contribute to the development of CKD. This study underscores the intricate relationship between obesity and CKD, revealing a high prevalence of CKD. Obesity, including overweight, abdominal obesity, AHTN, IFG, T2D, dyslipidemia, and hyperuricemia emerged as significant metabolic risk factors for CKD. Early identification of these risk factors is crucial for effective intervention strategies. Public health policies should integrate both pharmacological and non-pharmacological approaches to address obesity-related conditions and prevent kidney damage directly.

Mitigating Acetaminophen-Induced Kidney Injury: The Protective Role of Grape Seed and Peanut Skin Extracts through the iNOS/CYP2E1 Pathway.

The rising number of acute kidney injury cases worldwide due to acetaminophen (APAP) emphasizes the critical need for effective prevention strategies to counteract APAP's detrimental effects. This study examined the kidney-protective capabilities of ethanolic extracts from grape seeds and peanut skins (GSEE and PSEE, respectively) in comparison with silymarin in rats that experienced an APAP overdose. The phenolic compounds in these extracts were measured by using high-performance liquid chromatography (HPLC). In the experiment, Sixty adult male albino rats were divided into five groups of 12. The Control group received 0.5 mL of saline via a gastric tube. Group II received acetaminophen (APAP, 640 mg/kg per day via a gastric tube) to induce renal injury, following Ucar et al. and Islam et al. Groups III, IV, and V received silymarin (50 mg/kg), grape seed extract (200 mg/kg), and peanut skin extract (200 mg/kg), respectively, along with 640 mg of APAP/kg per day for 21 days. Post APAP treatment, significant increases in serum urea and creatinine levels were noted, along with notable decreases in the percentage of body weight gain. Furthermore, there were increases in oxidative stress and inflammatory markers in the kidney tissues, including heightened mRNA expressions of renal iNOS and CYP2E1, which were confirmed through histological studies. The administration of GSEE, PSEE, and silymarin mitigated these adverse effects, likely due to their high phenolic content, which is recognized for its antioxidant and anti-inflammatory effects. GSEE, in particular, showed efficacy comparable to that of silymarin. Molecular docking studies revealed that APAP impeded critical enzymes essential for cellular antioxidant defense, whereas the bioactive compounds in the grape seed and peanut skin extracts effectively inhibited key enzymes and receptors involved in inflammation and oxidative stress. These findings suggest that GSEE and PSEE could serve as viable alternative treatments for kidney damage induced by APAP. Further research to isolate and identify these effective compounds is recommended.

COVID-19 and kidney involvement: pathophysiological approach

Introduction: Due to the great threat posed by COVID-19, the scientific community must have evidence of kidney damage in patients affected by this disease, which would make it possible to carry out actions aimed at its prevention and early detection. Objectives: deepen knowledge about COVID-19 and its impact on the kidney. Methods: a bibliographic review on COVID-19 and kidney was carried out, in research published in Spanish and English, in the PubMed, Scielo, and Dialnet databases. All documents published in the last five years (2019-2023) were selected, which included the keywords: COVID-19, kidney, kidney disease. Conclusions: within the systemic involvement caused by COVID-19, the kidney plays a predominant role in its pathophysiology and as a target organ. Kidney disease is in itself a risk factor for morbidity and mortality and acute kidney failure worsens the prognosis; Hence, it is necessary to delve deeper into these topics every day to direct novel diagnostic and therapeutic strategies

Agricultural Pesticide-Induced Physiological Stresses in Freshwater Fishes of Bangladesh

In Bangladesh, most croplands are situated in floodplains, enriched by numerous rivers and extensive freshwater wetlands. These areas also support productive open-water fisheries, crucial for supplying protein, generating income, creating jobs, and boosting the GDP. However, the widespread use of pesticides in these floodplains to protect crops and enhance food production leads to significant environmental issues. Agricultural pesticide residues enter water bodies through runoff, rainwater, drainage, seepage, and spray drift, contaminating natural water bodies and exerting continuous stress on aquatic life, including fish. Previous studies have detected pesticide residues in surface waters, sediments, and fish in Bangladesh, posing a major threat to wetland ecosystems. Research on freshwater fish species in Bangladesh has highlighted toxic effects on fish gonads, such as adhesion, inter-follicular space degeneration, ovigerous lamellae degeneration, necrosis, degenerated perinucleolar oocytes, cytoplasmic retraction in ovaries, and damage to sertoli cells. Additional observed effects include irregularly shaped seminiferous tubules, breakage of seminiferous tubules, and empty lumens in testes. Pesticides also inflict harm on other internal organs of fish, with gill effects like clubbing, reduction of gill filaments, telangiectasia of gill lamellae, hemorrhage, and damage to gill rakers. Kidney and liver damage include necrosis, cellular tissue degradation, acute cellular swelling, and irregular renal corpuscles, along with autolysis, vacuolation, and fatty changes in the liver. Developing embryos and larvae of freshwater fish are particularly vulnerable to the toxic effects of agro-pesticides. Studies reveal acute toxicity during early life stages, evidenced by deformities like edema, notochord deformity, caudal fin damage, yolk sac damage, posterior region damage, tissue fragmentation, black pigmentation on the yolk, body curvature, and lordosis in larvae. Exposed embryos exhibit deformities such as dark brown yolk sacs, notochord deformities, and broken eggshells. Mortality rates of fish embryos and larvae escalate with higher pesticide concentrations in water. Haemato-biochemical parameters serve as crucial indicators of pesticide exposure in fish studies, showing alterations in blood hemoglobin, glucose, RBC, WBC counts, and various erythrocytic abnormalities like twin cells, fusion, echinocyte formation, spindle-shaped, tear-drop, and elongated cells. Nuclear abnormalities include binucleated cells, nuclear buds, nuclear bridges, karyopyknosis, and notched nuclei. Research suggests that even at low concentrations, agro-pesticides disrupt physiological functions and life history traits of fish, adversely impacting the natural productivity and biodiversity of freshwater fish in Bangladesh.

Alleviation of High-Fat Diet-Induced Hyperlipidemia in Mice by Stachys sieboldii Miq. Huangjiu via the Modulation of Gut Microbiota Composition and Metabolic Function.

Hyperlipidemia is a chronic disease that is difficult to cure, and long-term pharmacotherapy may have negative consequences. Dietary therapy is a very promising strategy, and Chinese rice wine (Huangjiu) will play an important role because of its many biologically active components. In this work, the alleviating effect of Stachys sieboldii Miq. Huangjiu (CSCHJ) on high-fat diet-induced hyperlipidemia in mice was investigated, which is brewed from the wheat Qu with the addition of Stachys sieboldii Miq. and contains 15.54 g/L of polysaccharides. The experimental results showed that CSCHJ inhibited appetite, reduced body weight and blood sugar levels, and downregulated the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) while concurrently upregulating high-density lipoprotein cholesterol (HDL-C) in the high-fat diet-induced hyperlipidemia mice. At the same time, it was discovered that alcohol worsens hyperlipidemia symptoms and related physiological markers, implying that CSCHJ polysaccharides may play a role in hyperlipidemia treatment. Through the assessment of organ indices, liver and kidney function, and tissue staining, CSCHJ demonstrated efficacy in repairing liver, kidney, and colon mucosal damage in hyperlipidemic mice. Furthermore, 16S rDNA sequencing and gas chromatography studies revealed that CSCHJ effectively restored the intestinal microbial structure and enhanced the quantity of fecal short-chain fatty acids (SCFAs) in hyperlipidemic mice. Therefore, the alleviating effect of CSCHJ on hyperlipidemia in mice may be attributed to its regulation of energy metabolism by repairing liver, kidney, and colon mucosal damage and restoring the gut microbiota structure, among other mechanisms. Overall, our findings provide evidence that CSCHJ contains active ingredients capable of alleviating hyperlipidemia, thereby laying a theoretical foundation for the extraction of bioactive substances from Huangjiu for future medical or dietary use.

CD11b suppresses TLR7-driven inflammatory signaling to protect against lupus nephritis.

Lupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role of CD11b, a protein encoded by the ITGAM gene, in the development of LN and its functional activation as a therapeutic strategy. Genetic coding variants of ITGAM significantly increase the risk for SLE and LN by producing a less active CD11b and leading to elevated levels of type I interferon (IFN I). However, a molecular mechanism for how these variants increase LN risk has been unclear. Here, we determined that these variants also significantly associate with elevations in soluble urokinase plasminogen activator receptor (suPAR), a known biomarker linked to kidney disease, suggesting a novel molecular connection. Pharmacologic activation of CD11b with a novel, clinical-stage agonist ONT01 significantly suppressed suPAR production in myeloid cells and reduced systemic inflammation and kidney damage in multiple experimental models of LN. Importantly, delaying treatment with ONT01 until after disease onset also significantly reduced serum suPAR and inflammatory cytokines, and decreased immune complex deposition in the glomerulus, glomerulonephritis and albuminuria, suggesting that CD11b activation is therapeutic for LN. Genetic activation of CD11b via a gain-of-function CD11b mutation also showed complete protection from LN, whereas genetic deletion of CD11b worsened the disease in mice, providing further evidence of the role of CD11b activation in regulating LN. Finally, transfer of human LN PBMCs generated human LN like disease in mice that was significantly reduced by ONT01. Together, these data provide strong evidence that ONT01 mediated CD11b activation can therapeutically modulate TLR7-driven inflammation and protect against LN. These findings support clinical development of CD11b agonists as novel therapeutics for treating lupus nephritis in human patients.

Hyperkalemia Incidence in Patients With Non-Dialysis Chronic Kidney Disease: A Large Retrospective Cohort Study From United States Clinical Care

Estimates of the incidence of hyperkalemia in patients with chronic kidney disease (CKD) vary widely. Our objective was to estimate hyperkalemia incidence in patients with CKD from routine clinical care, including by level of kidney damage or function and among important patient subgroups. Retrospective cohort study. 1,771,900 patients with stage 1-4 CKD identified from the US Optum De-Identified electronic health records database. Impaired kidney damage or function level at baseline based on urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), respectively, and selected patient subgroups. Hyperkalemia: 2 elevated serum potassium values (≥5.5mmol/L) from the inpatient setting (2-24 hours apart) or outpatient setting (maximum 7 days apart), or 1 elevated serum potassium value plus pharmacotherapy initiation or hyperkalemia diagnosis (maximum 3 days apart). Incidence rates of hyperkalemia were calculated. Estimates were stratified by UACR and eGFR level at baseline and patient subgroups. Over a mean follow-up of 3.9 years, the incidence of hyperkalemia was 3.37 events/100 person-years (95% confidence intervals, 3.36-3.38). Higher incidence rates were observed with increased UACR and lower eGFR. Highest rates were observed with UACR≥3,500 (up to 19.1/100 person-years) irrespective of decreased eGFR level. High rates also occurred in patients with type 2 diabetes mellitus (T2DM, 5.43/100 person-years), heart failure (8.7/100 person-years), and those prescribed steroidal mineralocorticoid receptor antagonists (sMRAs, 7.7/100 person-years). Potential misclassification of variables from possible medical coding errors; potential data incompleteness issues if patients received care at institutions not included in Optum. Hyperkalemia is a frequent occurrence in CKD, particularly in patients with T2DM, heart failure, or prescribed sMRAs, indicating the need for regular serum potassium and UACR monitoring in this patient population to help mitigate risk.

Artificial intelligence in chronic kidney diseases: methodology and potential applications.

Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions.