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The purpose of this study was to test the protective effect of Withania somnifera (WS) against the harmful effects of mercuric chloride (HgCl2)‐induced kidney failure at the histological, biochemical, and immune levels in Wistar rats. The study assessed the biochemical and immunological changes in five groups (n = 6): Group 1 (G1) was the negative control, and the other rats received a single subcutaneous dose of HgCl2 (2.5 mg/kg in 0.5 mL of 0.9% saline solution) and randomly divided into 4 groups. Group 2 (G2) was the positive control and left without treatment. Groups 3, 4, and 5 (G3, G4, and G5) were treated with different doses of WS root powder for 30 days. The HgCl2‐positive group showed significant signs of renal toxicity as reflected by increased levels of kidney function parameters (blood urea nitrogen, urea, and creatinine), inflammatory biomarkers, immunological indices (SDF‐1, IL‐6, NGAL, and KIM‐1), and oxidative stress (SOD, TAC, CAT, GSH, and MDA). The positive group rats also showed drastic pathological changes in renal tissues. Different doses of WS treatment significantly reduced the levels of all biochemical markers and decreased pathological damage to the kidney tissues. The antioxidant, phenolic, and flavonoid constituents of WS root powder helped protect rats' kidneys against HgCl2‐induced kidney toxicity in male rats. [ABSTRACT FROM AUTHOR]

Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid‐lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK‐52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM‐1 and caspase‐3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2‐mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP‐binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin‐treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO‐1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN. [ABSTRACT FROM AUTHOR]

Purpose: Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear. Methods: We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180 min of moderate-intensity work (200 W/m2) in temperate (wet-bulb globe temperature [WBGT] 16 °C) and hot (32 °C) environments in healthy young (n = 13, 22 years) and older men (n = 12, 59 years), and older men with type 2 diabetes (T2D; n = 9, 60 years) or hypertension (HTN; n = 9, 60 years). Results: There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82 ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22 pg/mL higher in the older relative to young group, increasing by ~ 10 pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40 min) and HTN (108 ± 42 min), elevations in NGAL and KIM1 were similar to their healthy counterparts. Conclusion: Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged. [ABSTRACT FROM AUTHOR]

Background: Polymyxins have been revived as a last-line therapeutic option for multi-drug resistant bacteria and continue to account for a significant proportion of global antibiotic usage. However, kidney injury is often a treatment limiting event with kidney failure rates ranging from 5 to 13%. The mechanisms underlying polymyxin-induced nephrotoxicity are currently unclear. Researches of polymyxin-associated acute kidney injury (AKI) models need to be more standardized, which is crucial for obtaining consistent and robust mechanistic results. Methods: In this study, male C57BL/6 mice received different doses of polymyxin B (PB) and polymyxin E (PE, also known as colistin) by different routes once daily (QD), twice daily (BID), and thrice daily (TID) for 3 days. We continuously monitored the glomerular filtration rate (GFR) and the AKI biomarkers, including serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). We also performed histopathological examinations to assess the extent of kidney injury. Results: Mice receiving PB (35 mg/kg/day subcutaneously) once daily exhibited a significant decrease in GFR and a notable increase in KIM-1 two hours after the first dose. Changes in GFR and KIM-1 at 24, 48 and 72 h were consistent and demonstrated the occurrence of kidney injury. Histopathological assessments showed a positive correlation between the severity of kidney injury and the changes in GFR and KIM-1 (Spearman's rho = 0.3167, P = 0.0264). The other groups of mice injected with PB and PE did not show significant changes in GFR and AKI biomarkers compared to the control group. Conclusion: The group receiving PB (35 mg/kg/day subcutaneously) once daily consistently developed AKI at 2 h after the first dose. Establishing an early and stable AKI model facilitates researches into the mechanisms of early-stage kidney injury. In addition, our results indicated that PE had less toxicity than PB and mice receiving the same dose of PB in the QD group exhibited more severe kidney injury than the BID and TID groups. [ABSTRACT FROM AUTHOR]

Abstract Background Polymyxins have been revived as a last-line therapeutic option for multi-drug resistant bacteria and continue to account for a significant proportion of global antibiotic usage. However, kidney injury is often a treatment limiting event with kidney failure rates ranging from 5 to 13%. The mechanisms underlying polymyxin-induced nephrotoxicity are currently unclear. Researches of polymyxin-associated acute kidney injury (AKI) models need to be more standardized, which is crucial for obtaining consistent and robust mechanistic results. Methods In this study, male C57BL/6 mice received different doses of polymyxin B (PB) and polymyxin E (PE, also known as colistin) by different routes once daily (QD), twice daily (BID), and thrice daily (TID) for 3 days. We continuously monitored the glomerular filtration rate (GFR) and the AKI biomarkers, including serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). We also performed histopathological examinations to assess the extent of kidney injury. Results Mice receiving PB (35 mg/kg/day subcutaneously) once daily exhibited a significant decrease in GFR and a notable increase in KIM-1 two hours after the first dose. Changes in GFR and KIM-1 at 24, 48 and 72 h were consistent and demonstrated the occurrence of kidney injury. Histopathological assessments showed a positive correlation between the severity of kidney injury and the changes in GFR and KIM-1 (Spearman’s rho = 0.3167, P = 0.0264). The other groups of mice injected with PB and PE did not show significant changes in GFR and AKI biomarkers compared to the control group. Conclusion The group receiving PB (35 mg/kg/day subcutaneously) once daily consistently developed AKI at 2 h after the first dose. Establishing an early and stable AKI model facilitates researches into the mechanisms of early-stage kidney injury. In addition, our results indicated that PE had less toxicity than PB and mice receiving the same dose of PB in the QD group exhibited more severe kidney injury than the BID and TID groups.

Psoriasis is a common systemic inflammatory disease and the literature has reported varying results regarding the renal involvement of psoriasis. Although many studies have investigated the presence of chronic renal damage in patients with psoriasis, there are few studies demonstrating subclinical renal damage. The aim of this study was to prospectively evaluate the presence of clinical and subclinical renal damage in patients with psoriasis vulgaris (PV). The study prospectively enrolled 44 PV patients and 44 healthy controls. Serum urea (BUN), creatinine levels, glomerular filtration rate (GFR), complete urinalysis, urine microscopy and subclinical renal damage markers albuminuria, proteinuria, urinary kidney injury molecule-1 (uKIM-1)/creatinine, urinary neutrophil gelatinase-associated lipocalin (uNGAL)/creatinine and urinary podocalyxin/creatinine levels were measured and compared in both groups.Proteinuria levels were found to be statistically significantly higher in patients with PV (p = 0.021). A positive correlation was observed between proteinuria levels and uKIM-1/creatinine, uNGAL/creatinine and albuminuria levels in the patient group (p = 0.013, r = 0.373; p = 0.017, r = 0.358; p = 0.017, r = 0.358, respectively). This study concluded that PV does not cause clinical kidney injury. Increased proteinuria in PV patients supports the presence of subclinical renal damage. Regular monitoring of proteinuria and uKIM-1/creatinine, uNGAL/creatinine and albuminuria levels, which are positively correlated with proteinuria, may allow early detection of renal damage in PV patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION. The determination of nephrotoxicity markers is a useful and necessary step in the detection of renal injury in animal experiments; these markers help accurately localise organ damage. With multiple damaging agents, known nephrotoxicity mechanisms, and laboratory animal species, there is currently no widely accepted renal injury marker that meets all the prerequisites.AIM. This study aimed to collate literature data on nephrotoxicity markers, evaluate their prognostic significance, and formulate general recommendations for assessing urinary system function in preclinical studies.DISCUSSION. This article describes a comparative analysis of the nephrotoxicity markers recommended by regulatory authorities for monitoring drug-induced kidney injury. According to the results, the most commonly used and prognostically significant markers of acute kidney injury in preclinical studies are cystatin C, albumin, total protein, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin-2 (NGAL), and clusterin. Chronic kidney injury markers include the above, plus the glomerular filtration rate, creatinine, urea, and osteopontin. An electrolyte panel can be used for the differential diagnosis of pre-renal azotaemia and acute kidney injury. Potential limitations for the routine use of kidney injury markers in preclinical research include the high cost of their quantitative determination and the lack of information on the applicability of data obtained from different species of laboratory animals.CONCLUSIONS. Having compared the prognostic significance of common biomarkers, the authors provided general recommendations for a comprehensive preclinical assessment of urinary system function, including laboratory investigations, instrument-based tests, and necropsy. A preclinical study design should be based on the study aims, the species and number of animals used, and special considerations for the test article.

Abstract Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity.

Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. Material and methods: This case–control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). Results: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. Conclusions: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients. [ABSTRACT FROM AUTHOR]

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice. [ABSTRACT FROM AUTHOR]

Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity. [ABSTRACT FROM AUTHOR]

Abstract Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p

Background & objective: chronic kidney disease (CKD) is a long-term condition in which the kidney function is gradually lost over time, which includes filtration of waste products and excess fluids from the bloodstream, maintaining electrolytes balance and produce hormones that regulate blood pressure and stimulate red blood cell production. The target of management for CRF (CRF) is to restrict the injury to the kidneys, usually by detection of its underlying cause. The current study aimed to detect and relate biomarker levels, such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and Kidney Injury Molecule type 1 (KIM-1) in patients with CKD. Methodology: Ninety participants took part in the study between Sep 2023 and Jan 2024 through random sampling. They were divided into two groups; Group-1 included 45 healthy volunteers, and Group-2 included 45 individuals with CKD, stage 1 to end stage renal failure and were on dialysis. The ELISA method was used to measure the serum levels of NGAL and KIM-1 in each person. Colorimetric techniques were used to measure creatinine, potassium, calcium, serum urea, and random blood sugar (RBS). Version 25 of IBM's statistical software for the social sciences (SPSS) on a Windows platform was used to conduct the statistical study. Using the analysis of variance student t test, patients with CKD were compared to a healthy group; a P ≤ 0. 05 indicated statistical significance. Results: Between individuals with chronic kidney disease and the healthy group, there was a statistically significant variance in NGAL and KIM_1, serum creatinine, urea, potassium, calcium, and RBS. Conclusion: Patients with CRF had considerably higher levels of Neutrophil Gelatinase Associated Lipocalin (NGAL) and Kidney Injury Molecule type 1 (KIM-1), which are diagnostic markers. [ABSTRACT FROM AUTHOR]

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hyperglycemia-induced oxidative stress plays a crucial role in the development of diabetic nephropathy (DN). Moreover, adverse extracellular matrix (ECM) accumulation elevates renal resistive index leading to progressive worsening of the pathology in DN. Nimbidiol is an alphaglucosidase inhibitor, isolated from the medicinal plant, ‘neem’ (Azadirachta indica) and reported as a promising anti-diabetic compound. Previously, a myriad of studies demonstrated an anti-oxidative property of a broadspectrum neem-extracts in various diseases including diabetes. Our recent study has shown that Nimbidiol protects diabetic mice from fibrotic renal dysfunction in part by mitigating adverse ECM accumulation. However, the precise mechanism remains poorly understood. Methods: The present study aimed to investigate whether Nimbidiol ameliorates renal injury by reducing oxidative stress in type-1 diabetes. To test the hypothesis, wild-type (C57BL/6J) and diabetic Akita (C57BL/6-Ins2Akita/J) mice aged 10–14 weeks were used to treat with saline or Nimbidiol (400 μg kg−1 day−1 ) for 8 weeks. Results: Diabetic mice showed elevated blood pressure, increased renal resistive index, and decreased renal vasculature compared to wild-type control. In diabetic kidney, reactive oxygen species and the expression levels of 4HNE, p22phox, Nox4, and ROMO1 were increased while GSH: GSSG, and the expression levels of SOD-1, SOD-2, and catalase were decreased. Further, eNOS, ACE2, Sirt1 and IL-10 were found to be downregulated while iNOS and IL-17 were upregulated in diabetic kidney. The changes were accompanied by elevated expression of the renal injury markers viz., lipocalin-2 and KIM-1 in diabetic kidney. Moreover, an upregulation of p-NF-κB and a downregulation of IkBα were observed in diabetic kidney compared to the control. Nimbidiol ameliorated these pathological changes in diabetic mice. Conclusion: Altogether, the data of our study suggest that oxidative stress largely contributes to the diabetic renal injury, and Nimbidiol mitigates redox imbalance and thereby protects kidney in part by inhibiting NF-κB signaling pathway in type1 diabetes. [ABSTRACT FROM AUTHOR]

In this study, we assessed the impact of commercially available polymyxin B against VRP-034 (novel formulation of polymyxin B) using a validated in vitro human renal model, aProximateTM. Freshly isolated primary proximal tubule cells (PTCs) were cultured in Transwell plates and treated with various concentrations of the formulations for up to 48 h. The functional expression of megalin–cubilin receptors in PTC monolayers was validated using FITC-conjugated albumin uptake assays. Polymyxin B and VRP-034 were evaluated at six concentrations (0.3, 1, 3, 10, 30, and 60 µM), and nephrotoxicity was assessed through measurements of transepithelial electrical resistance (TEER), intracellular adenosine triphosphate (ATP) levels, lactate dehydrogenase (LDH) release, and novel injury biomarkers [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and clusterin]. Additionally, histological analysis using annexin V apoptosis staining was performed. Our results indicated a significant decrease in TEER with polymyxin B at concentrations ≥10 μM compared to VRP-034. Toxic effects were observed from ATP and LDH release only at concentrations ≥30 μM for both formulations. Furthermore, injury biomarker release was higher with polymyxin B compared to VRP-034, particularly at concentrations ≥10 µM. Histologically, polymyxin B-treated PTCs showed increased apoptosis compared to VRP-034-treated cells. Overall, VRP-034 demonstrated improved tolerance in the aProximateTM model compared to polymyxin B, suggesting its potential as a safer alternative for renal protection. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effects of the antioxidant thymoquinone on treated and untreated kidneys on histological and oxidative parameters as well as Kidney Injury Molecule (KIM-1) levels in an experimental unilateral ureteropelvic junction obstruction (UPJO) with resultant hydronephrosis (HN) model. In adherence to the Animal research: reporting of in vivo exepriments guidelines, 34 male Wistar rats were randomly divided into four groups which were named accordingly: "CO" (corn oil), "TQ" (thymoquinone and corn oil), "HNCO" (UPJO-HN and corn oil), "HNTQ" (UPJO-HN, thymoquinone and corn oil). Histologically, pelvic epithelial damage, glomerular shrinkage and sclerosis, tubular damage, interstitial edema-inflammation-fibrosis (IEIF), and vascular congestion were assessed. Biochemically, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GR) and KIM-1 levels were assessed. Macroscopic HN developed in all obstructed kidneys. Ipsilateral obstructed kidneys deteriorated in all histological parameters. Thymoquinone attenuated glomerular shrinkage and sclerosis alterations but increased vascular congestion. Contralateral non-obstructed kidneys also showed histological deterioration. Thymoquinone had beneficial effects in terms of IEIF presence in contralateral kidneys but it increased vascular congestion. MDA and SOD results were inconclusive. UPJO caused decreased GR levels in the ipsilateral kidneys but not in the contralateral ones. This effect was not ameliorated by thymoquinone treatment. KIM-1 levels were increased in ipsilateral obstructed kidneys with a lower level in HNTQ group than in HNCO. KIM-1 level of the ipsilateral HNTQ group was higher than in both non-obstructed ipsilateral kidney groups. The effect of thymoquinone in ameliorating bilaterally observed histological alterations was limited and controversial. Oxidative damage detected by GR measurements was not prevented by thymoquinone. Thymoquinone partially decreased the damage as evidenced by reduced KIM-1 levels in thymoquinone-treated obstructed kidneys. [ABSTRACT FROM AUTHOR]

Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Simple Summary: The concept of the cardio–renal axis is based on the assumption that kidney dysfunction is a secondary consequence of heart disease, a mechanism observed in dilated cardiomyopathy (DCM). Traditional serum markers are not always effective, especially in the early stages of kidney disease. Thus, there is a need to find more sensitive measures of renal impairment during heart failure. The selected biomarkers, cystatin C, KIM-1 (kidney injury molecule-1), and NGAL (neutrophil gelatinase-associated lipocalin), were evaluated in a study for their efficacy as indicators of early kidney damage in dogs with dilated cardiomyopathy. The serum concentrations of these biomarkers and their creatinine ratio were measured and analyzed to determine their diagnostic values. This study's findings suggest that during the asymptomatic phase of dilated cardiomyopathy, only NGAL concentration and the NGAL/creatinine ratio may serve as diagnostic markers for early-stage kidney injury. The above markers can, therefore, be used in the early diagnosis of kidney diseases in dogs with asymptomatic DCM. Heart and kidney diseases are among the most frequent medical conditions diagnosed in small animals. Due to the functional interconnection between these organs, the concept of the cardio–renal axis has been developed. In this context, renal disease or dysfunction often occurs secondary to heart diseases, such as dilated cardiomyopathy (DCM). DCM is the most common cardiomyopathy and a leading cause of mortality in large-breed dogs. Traditional biomarkers like creatinine or symmetric dimethylarginine concentration are not always effective, especially in the early stages of the disease, underscoring the need for more sensitive markers of renal impairment during heart failure (HF). This study aimed to evaluate the efficacy of selected biomarkers as indicators for early kidney damage in dogs with stage B2 DCM. We measured serum concentrations of cystatin C, KIM-1 (kidney injury molecule-1), and NGAL (neutrophil gelatinase-associated lipocalin) and their ratios to creatinine, analyzing their diagnostic values. Cystatin C was quantified using a sandwich enzyme immunoassay, while KIM-1 and NGAL were measured with enzyme-linked immunosorbent assay kits designed for canine diagnostics. The concentrations were indexed against serum creatinine. The study included 26 dogs: 9 with HF and 17 healthy controls. The mean ± standard deviation for healthy dogs for cystatin C, cystatin C/creatinine ratio, KIM-1, KIM-1/creatinine ratio, NGAL, and NGAL/creatinine ratio were 0.24 ± 0.04, 0.26 ± 0.07, 0.61 ± 0.07, 0.67 ± 0.13, 2.76 ± 1.8, and 2.79 ± 1.81, respectively. For DCM dogs, these values were 0.27 ± 0.1, 0.32 ± 0.12, 0.61 ± 0.08, 0.69 ± 0.17, 6.46 ± 5.22 (p = 0.02), and 7.99 ± 6.53 (p = 0.04). This study's findings suggest that during the asymptomatic phase of DCM, only NGAL concentration and the NGAL/creatinine ratio may serve as diagnostic markers for early-stage kidney injury. [ABSTRACT FROM AUTHOR]

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m². We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m²). We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants. [ABSTRACT FROM AUTHOR]

Furan (FU) is a common food contaminant and environmental pollutant. While cadmium (Cd) is a prevalent environmental contaminant that poses a risk to the health of humans and animals. The goal of the current study was to assess the combined effects of FU and Cd on the kidney of male albino rats. Five groups of rats were designed: Cr-water, Cr-oil, FU (16 mg/kg b.w), Cd (2 mg/kg b.w), and FU+Cd, rats were co-treated with both FU and Cd. All treatments were given orally for 30 days. Renal function testing revealed severe biochemical changes in the rats, indicating substantial tissue injury. In addition, there was a notable rise in malondialdehyde (MDA) levels and a fall in reduced glutathione (GSH) concentration as well as the activity of superoxide dismutase (SOD) and catalase (CAT). Also, prominent histopathological alterations in renal tissues were noticed. Additionally, FU and/or Cd significantly up-regulated the expression profile of Kim-1, and inflammatory markers (TNF-α and iNOS). Meanwhile, Aqp1, and Aqp2 m-RNA genes expression were significantly downregulated along with significant upregulation of apoptotic proteins (PCNA). Intriguingly, the concurrent FU and Cd intoxication elicited additional extensive renal injury than their individual exposure. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have shown that hypohydration can increase renal injury. However, the contribution of hypohydration to the extent of renal injury is often confounded by exercise induced muscle damage. Therefore, the aim of the present study was to investigate the effect of manipulating hydration status during moderate-intensity cycling in the heat on biomarkers of renal injury. Methods: Following familiarisation, fourteen active males (age: 21 [20–22] y; BMI: 22.1 ± 1.9 kg/m2; V ˙ O2peak: 55 ± 9 mL/kg/min) completed two experimental trials, in a randomised cross-over design. Experimental trials consisted of up to 120 min of intermittent cycling (~ 50% Wpeak) in the heat (~ 35 °C, ~ 50% relative humidity). During exercise, subjects consumed either a water volume equal to 100% body mass losses (EU) or minimal water (HYP; 75–100 mL) to induce ~ 3% body mass loss. Blood and urine samples were collected at baseline, 30 min post-exercise and 24 h post-baseline, with an additional urine sample collected immediately post-exercise. Results: Thirty minutes post-exercise, body mass and plasma volume were lower in HYP than EU (P < 0.001), whereas serum and urine osmolality (P < 0.001), osmolality-corrected urinary kidney injury molecule-1 concentrations (HYP: 2.74 [1.87–5.44] ng/mOsm, EU: 1.15 [0.84–2.37] ng/mOsm; P = 0.024), and percentage change in osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (HYP: 61 [17–141] %, EU: 7.1 [– 4 to 24] %; P = 0.033) were greater in HYP than EU. Conclusion: Hypohydration produced by cycling in the heat increased renal tubular injury, compared to maintaining euhydration with water ingestion. [ABSTRACT FROM AUTHOR]

With an increasing number of marginal donors, additional methods for the evaluation of cadaveric kidney quality are required. This study aimed to evaluate pretransplant deceased donor serum (s) and urine (u) biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18, and C-X-C motif chemokine 10 (CXCL10) for predicting early and late graft function. In total, 43 deceased kidney donors and 76 corresponding recipients were enrolled. Delayed graft function (DGF) occurred in 27.6% of cases. sIL-18, sKIM-1, uNGAL, and uKIM-1 were predictors of DGF. A model incorporating sIL-18, uKIM-1, and clinical factors was developed to predict DGF (AUROC 0.863). Univariate analysis showed a negative association between uKIM and graft eGFR at 6, 12, 24, and 36 months, but this was not confirmed in the multivariate analysis. In conclusion, we report a superior performance of donor biomarkers for predicting DGF and later graft function over serum creatinine. Higher levels of donor sIL-18 and uKIM in conjunction with expanded-criteria donors and longer cold ischemia times predicted DGF. With no renal tubular damage in zero-time donor biopsies, higher pretransplant urine and serum NGAL levels were associated with better allograft function one year after transplantation, and sNGAL with graft function three years after transplantation. [ABSTRACT FROM AUTHOR]

Advanced age, called geriatrics, negatively affects the aging–related physiological changes on bodysystems. non–steroidal anti–inflammatory drugs (NSAIDs) used in geriatric pets or humans have negative effects on the kidneys. For this purpose, , the effects of Meloxicam and Flunixin Meglumine, which are NSAIDs frequently used in Veterinary Medicine, on the liver and kidney structure and function in geriatric male rats were evaluated. Twenty–four male geriatric rats (30–36 month old) and twenty–four 3–month–old young male Wistar albino rats were used in the study. Six groups were created, with eight rats in each group: young control (YC), young Meloxicam (YM), young Flunixin Meglubine (YFM), geriatric control (GC), geriatric meloxicam (GM), geriatric Flunixin Meglubine (GFM). Control groups (YC and GC) received an intraperitoneal injection of saline using the same volume as in the othergroups. Meloxicam was administered at 5.8 mg·kg-1 to the YM and GM groups, and Flunixin Meglumine at 2.5 mg·kg-1 intraperitoneally to the YFM and GFM groups once a day for 5 days. Neutrophil Gelatinase–Associated Lipocalin (NGAL), Cystatin C (Cyc–c), Kidney Injury Molecule–1 (KIM–1), Interleukin–18 (IL–18), Urea, Creatinine (Crea), Albumin (Alb), and Total Protein (TP) levels, were determined in sera and urine samples. Serum NGAL, Cys–C, and KIM–1 levels in the GC group were found to be significantly higher than those in the YC group (P

Rishabh Singh,1 James C Watchorn,2 Alexander Zarbock,3 Lui G Forni4,5 1Department of Surgery, Royal Surrey Hospital, Guildford, Surrey, UK; 2Intensive Care Unit, Royal Berkshire NHS Foundation Trust, Reading, Berkshire, UK; 3Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany; 4Critical Care Unit, Royal Surrey Hospital, Guildford, Surrey, UK; 5School of Medicine, Kate Granger Building, University of Surrey, Guildford, UKCorrespondence: Lui G Forni, Email luiforni@nhs.netAbstract: Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed “novel” biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients’ postoperative care.Plain Language Summary: Kidney damage is common after major surgery with a recent study showing almost 1 in 5 patients suffer kidney damage. The usual tests for measuring kidney function are excellent in the outpatient but not so good in acute scenario’s. Therefore, there has been a lot of interest in new markers of kidney damage (so-called novel biomarkers) which perform well acutely and allow earlier detection of damage allowing treatment to be started earlier. This article summarises the currently available biomarkers for use post-operatively and points out the different information that can be achieved by using them routinely.Keywords: acute kidney injury, biomarkers, DKK-3, dickkopf-3, suPAR, soluble urokinase plasminogen activator receptor, IGFBP-7, insulin growth factor binding protein-7 and TIMP-2, tissue inhibitor of metalloproteinases-2, PENK, proenkephalin A 119-159, NGAL, neutrophil gelatinase-associated lipocalin, KIM-1, kidney injury molecule-1, CCL14, chemokine 14

Introduction: Cyclosporin A (CsA) is a drug used to suppress the immune system thus treating rejection of transplantation and autoimmune diseases. However, adverse effects limit its use in clinical practice. PRP is an autologous growth factor-rich product that appeared useful as a product allowing regeneration of tissues by releasing growth factors that alleviate destruction of tissues. Material and Methods: Forty adult male albino rats were involved in this work. They were classified into four equal groups; control, sham control, CsA-treated, Cyclosporine A-PRP treated. Histological (H & E and Masson's trichrome), immunohistochemical (caspase-3 and TGFβ-1), biochemical assessment (serum urea, create, tissue level of Glutathione reductase, SOD and MDA, and tissue expression of KIM-1 and NAG) were performed. Results: In CsA treated group, renal cortex revealed shrunken segmented glomerulus with darkly stained nuclei, widened urinary space, interstitial hemorrhage, and intraluminal casts. Other sections showed hypercellular glomerulus with extremely narrow urinary space, intraglomerular hemorrhage, tubular vacuolations and karyolysis. Also, there existed too much accumulation of collagen fibers around and within glomeruli in addition to around the tubules in group III. Immunohistochemically, Sections from group III showed strong positive reaction of caspase-3 and TGFβ-1. Biochemically there was elevated serum urea, creatinine, and tissue MDA level together with decreased tissue level SOD and Glutathione reductase in group III. PRP could ameliorate histopathological nephrotoxic effects induced by CsA. As well as improving biochemical markers and gene expression values. Conclusion: PRP appeared to be a safe product and could be used to reverse the adverse effects induced by CsA administration. [ABSTRACT FROM AUTHOR]

Thalassemia is a genetic disease identified by a defect in the production of one or more globin chains. This study was aimed at determining the possibility of using "serum kidney injury molecule-1 (KIM-1)" and "N-acetyl-β-D-glucosaminidase (NAG)" in the diagnosis of early renal damage in thalassemia patients. Serum biomarkers (CBC, urea, creatinine, KIM-1, and NAG) were determined in 45 patients with major thalassemia with an age range of 4-45 years who attended Baquba General Hospital. A significant increase in S.KIM-1 and S.NAG levels in patients compared with controls. The level of KIM was positively correlated with that of urea and creatinine in comparison with control. Also, the level of NAG was strongly positively correlated with the level of KIM-1 (p = 0.000) and had a moderately positive correlation with urea and creatinine (p = 0.000). According to ROC, KIM-1 had a sensitivity of 95.56% and a specificity of 88.89%, while NAG had a sensitivity of 100% and a specificity of 75.6%. This study concluded that S.KIM-1 and S.NAG are highly promising biomarkers for the detection of "acute kidney injury" in an early stage before elevated urea and creatinine in thalassemia patients. [ABSTRACT FROM AUTHOR]

Vinpocetine (VIN) is a synthetic drug derived from the natural alkaloid vincamine. The antioxidation and anti‐inflammation effects of VIN allow it to be used for multiple therapeutic purposes. So, the research aims to discover the possibility of using VIN to improve the nephrotoxicity of acrylamide (ACR). Twenty‐four male albino rats were used in the trial: rats in the control group received 0.5 mL of oral saline, rats in the VIN group received an oral dose of VIN (5 mg/kg), rats in the ACR group received an oral dose of ACR (38.27 mg/kg), and rats in the VIN + ACR group received VIN and then ACR 1 h later. Rat blood and kidneys were collected 10 days after the experiment began to assess biochemical parameters and to examine both renal histopathological and immunohistochemistry. The ACR‐treated rats showed high levels of serum kidney function biomarkers (creatinine, urea, and uric acid), serum protein biomarkers (total protein, albumin, and globulin), renal kidney injury molecule (KIM)−1, renal malondialdehyde (MDA), and renal caspase‐3 immunoexpression. Moreover, ACR lowed both renal superoxide dismutase (SOD) activity and renal glutathione (GSH) level and caused renal histological alterations. While administration of VIN improved serum kidney function biomarkers, serum protein biomarkers, renal KIM‐1, renal oxidative stress biomarkers (MDA, SOD, and GSH), renal caspase‐3 immunoexpression, and renal histological alterations induced by ACR. The study confirmed the ability of VIN to reduce the nephrotoxic effects of ACR, which was evident through the results of biochemical parameters and histological and immunohistochemical examinations of the kidney tissues. Highlights: Vinpocetine (VIN) improved acrylamide (ACR)‐induced nephrotoxicity.VIN ameliorated serum kidney function and protein biomarkers in ACR‐treated rats.VIN improved renal KIM‐1, oxidative stress, histopathological alterations and caspase‐3 immunoexpression induced by ACR. [ABSTRACT FROM AUTHOR]

Normalization of urinary biomarkers of kidney injury is a common practice in clinical and research settings to account for variations in urine concentration, and urinary creatinine is often used as a reference. However, to date, there is no consensus on the adjustment of urinary biomarkers with creatinine, and both absolute and creatinine-adjusted biomarker levels are adopted for making interpretations of kidney health. Hence, the present study aimed to investigate the associations of urinary creatinine with three widely used kidney injury biomarkers, KIM-1, NGAL, and cystatin C, to validate the applicability of urinary creatinine as a reference for normalization. A cross-sectional study was performed with 2100 students, 10–18 years of age in the Children's Kidney Environmental Exposure Study (C-KidnEES) cohort established in Sri Lanka. As identified in linear regression analyses, normalization of urinary KIM-1, NGAL, and Cys-C to urinary creatinine did not result in significant under-adjustment or over-adjustment to the absolute urinary concentrations, giving no specific rationale for creatinine adjustment. Hence, absolute urinary concentrations of the above biomarkers can be adopted for the characterization of subclinical kidney injury in adolescents in community studies where early morning urine sampling is practiced. However, for spot urine samples, consideration of both absolute and creatinine-adjusted biomarker levels would be a better approach. [ABSTRACT FROM AUTHOR]

IntroductionChronic hyperglycemia-induced oxidative stress plays a crucial role in the development of diabetic nephropathy (DN). Moreover, adverse extracellular matrix (ECM) accumulation elevates renal resistive index leading to progressive worsening of the pathology in DN. Nimbidiol is an alpha-glucosidase inhibitor, isolated from the medicinal plant, ‘neem’ (Azadirachta indica) and reported as a promising anti-diabetic compound. Previously, a myriad of studies demonstrated an anti-oxidative property of a broad-spectrum neem-extracts in various diseases including diabetes. Our recent study has shown that Nimbidiol protects diabetic mice from fibrotic renal dysfunction in part by mitigating adverse ECM accumulation. However, the precise mechanism remains poorly understood.MethodsThe present study aimed to investigate whether Nimbidiol ameliorates renal injury by reducing oxidative stress in type-1 diabetes. To test the hypothesis, wild-type (C57BL/6J) and diabetic Akita (C57BL/6‐Ins2Akita/J) mice aged 10–14 weeks were used to treat with saline or Nimbidiol (400 μg kg−1 day−1) for 8 weeks.ResultsDiabetic mice showed elevated blood pressure, increased renal resistive index, and decreased renal vasculature compared to wild-type control. In diabetic kidney, reactive oxygen species and the expression levels of 4HNE, p22phox, Nox4, and ROMO1 were increased while GSH: GSSG, and the expression levels of SOD-1, SOD-2, and catalase were decreased. Further, eNOS, ACE2, Sirt1 and IL-10 were found to be downregulated while iNOS and IL-17 were upregulated in diabetic kidney. The changes were accompanied by elevated expression of the renal injury markers viz., lipocalin-2 and KIM-1 in diabetic kidney. Moreover, an upregulation of p-NF-κB and a downregulation of IkBα were observed in diabetic kidney compared to the control. Nimbidiol ameliorated these pathological changes in diabetic mice.ConclusionAltogether, the data of our study suggest that oxidative stress largely contributes to the diabetic renal injury, and Nimbidiol mitigates redox imbalance and thereby protects kidney in part by inhibiting NF-κB signaling pathway in type-1 diabetes.

Objective(s): Neuropathy, retinopathy, and nephropathy, known as the triopathy of diabetes, are the consequences of microvascular complications of diabetes. The present study aimed to investigate the potential protective effects of oleanolic acid (OA) administration against diabetic nephropathy considering biochemical and histopathological parameters.Materials and Methods: The rats with fasting blood glucose levels of 200 mg/dl and above were considered diabetic after induction of diabetes via injecting STZ. The other half of the rats were not injected with STZ (healthy rats). Both healthy and diabetic rats were then divided randomly into two subgroups to be administered with either OA (5 mg/kg) with 1 ml tap water by oral gavage or 1 ml tap water in the same route for 21 days. Serum urea-N, Ca, P, and Mg as well as renal tissue MDA, SOD, NF-κB, IL-6, IL-18, AMPK, YKL-40, and KIM-1 levels were measured.Results: OA administration partially decreased levels of serum urea-N and P, as well as levels of renal tissue MDA and inflammation markers (NF-κB, IL-6, IL-18, YKL-40, and KIM-1) in the diabetic rats. It also partially increased serum Ca and renal tissue AMPK levels in diabetic rats. These positive effects were also seen in renal tissue histopathology.Conclusion: OA treatment partially alleviated renal damage inflammatory and oxidative profiles in diabetic rats.

Background: Acromegaly is a rare disorder caused by excessive growth hormone (GH) secreted from a pituitary tumor. High levels of GH and insulin growth factor-1 can lead to renal hypertrophy, as well as to diabetes mellitus and hypertension, which negatively impact kidney function. It is believed that high GH may also be involved in the onset of diabetic nephropathy, the main cause of end-stage kidney disease in developed countries. Material and methods: This case–control study was conducted on 23 acromegalic patients and on a control group represented by 21 healthy subjects. The following parameters were determined for all the subjects: serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), nephrin and kidney injury molecule 1 (KIM-1). Results: Patients with acromegaly showed higher levels of UACR and lower levels of eGFR as compared to healthy subjects. No significant correlations were found between clinical or biochemical parameters associated with acromegaly and nephrin or KIM-1. Conclusions: There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients.

Background: Chronic kidney disease (CKD) affects more than 800 million people worldwide and is one of the leading non-communicable causes of death. Despite being a latent issue, once renal damage has started, the disease can rapidly progress to an advanced stage. Aims and Objectives: Currently, the most commonly used markers for the diagnosis of renal disease are non-specific and insensitive. As a result, the goal of the current study is to investigate whether KIM-1 could be a precise and sensitive biomarker for identifying early kidney injury in CKD patients. Materials and Methods: This case–control study recruited 155 participants from the Index Medical College Hospital v Research Centre, Indore, Madhya Pradesh, based on inclusion and exclusion criteria. 150 non-CKD subjects matched for age and sex were also taken from the hospital. The levels of KIM-1 were compared between CKD and non-CKD participants. Serum creatinine, urea, and creatinine clearance were also measured. Results: The levels of KIM-1 were substantially higher in CKD patients than in non-CKD participants. In addition, a negative relationship between KIM-1 and creatinine clearance was observed with a P

Background: Diabetic kidney disease (DKD) stands as a primary contributor to end-stage renal disease, associated with heightened mortality in cardiovascular diseases. This study aimed to explore the impact of an eight-week high-intensity interval training (HIIT) on renal injury in diabetic rats. Methods: Twenty-eight male Wistar rats were randomly allocated into four groups: healthy control (CTL), diabetic control (DC), exercise (EX), and diabetes-exercise (D + EX). Induction of diabetes in the DC and D + EX groups occurred through a two-month high-fat diet followed by a single dose of 35 mg/kg streptozotocin (STZ). Rats in the EX and D + EX groups underwent 4–10 intervals of HIIT (80–100% Vmax) over 8 weeks. Subsequently, pathological and biochemical parameters were assessed in the serum and kidney tissue of the experimental groups. Results: In the DC group, diabetes led to elevated kidney damage, glomerulosclerosis, fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index, animal weight, kidney dysfunction, albuminuria, and glomerular filtration rate. Additionally, serum and kidney levels of fetuin-A increased, along with kidney levels of KIM-1. Mechanistically, diabetes induction resulted in kidney inflammation by elevating levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-β), and interleukin 6 (IL-6), while reducing IL-10 levels and increasing the IL-6/IL-10 ratio. Furthermore, diabetes triggered renal oxidative stress, evidenced by increased Malondialdehyde (MDA) levels and decreased levels of glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). HIIT mitigated the adverse effects of diabetes in the D + EX group compared to the DC group. Conclusion: Our findings suggest that HIIT ameliorates type 2 diabetes (T2D)-induced kidney damage by mitigating inflammation, lowering serum levels of fetuin-A, and bolstering antioxidant defenses. This study highlights the potential of HIIT as a time-efficient intervention for diabetic nephropathy.

Herein, we measured the antidiabetic and nephroprotective effects of the sodium–glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Numerous studies have evaluated the beneficial effects of omega-3 fatty acids on inflammatory, autoimmune and renal diseases. However, data about the effects of omega-3 fatty acids on diabetic kidney disease in type 1 diabetes mellitus (T1DM) are lacking. This randomized-controlled trial assessed the effect of oral omega-3 supplementation on glycemic control, lipid profile, albuminuria level, kidney injury molecule-1 (KIM-1) and carotid intima media thickness (CIMT) in pediatric patients with T1DM and diabetic nephropathy. Seventy T1DM patients and diabetic nephropathy were enrolled with a mean age 15.2 ± 1.96 years and median disease duration 7 years. Patients were randomly assigned into two groups; intervention group which received oral omega-3 fatty acids capsules (1 g daily). The other group received a matching placebo and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c, fasting lipids, urinary albumin creatinine ratio (UACR), KIM-1 and CIMT. After 6 months, omega-3 fatty acids adjuvant therapy for the intervention group resulted in a significant decrease in FBG, HbA1c, triglycerides, total cholesterol, LDL-cholesterol, UACR, KIM-1 and CIMT, whereas, HDL-cholesterol was significantly higher post-therapy compared with baseline levels and compared with the control group (p < 0.05). Baseline KIM-1 levels were positively correlated to HbA1c, UACR and CIMT. Supplementation with omega-3 fatty acids was safe and well-tolerated. Omega-3 fatty acids as an adjuvant therapy in pediatric T1DM patients with diabetic nephropathy improved glycemic control, dyslipidemia and delayed disease progression and subclinical atherosclerosis among those patients. This trial was registered under ClinicalTrials.gov Identifier no. NCT05980026. • We assessed the role of omega-3 fatty acids in pediatric T1DM patients with nephropathy. • Omega-3 fatty acids improved glycemic control in T1DM patients. • Omega-3 fatty acids decreased microalbuminuria and kidney injury molecule-1 levels in T1DM. • CIMT was decreased after 6 months of omega-3 fatty acids supplementation. • Omega-3 fatty acids are safe effective adjuvant therapy for pediatric diabetic nephropathy. [ABSTRACT FROM AUTHOR]

In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries. [ABSTRACT FROM AUTHOR]

Objective(s): Neuropathy, retinopathy, and nephropathy, known as the triopathy of diabetes, are the consequences of microvascular complications of diabetes. The present study aimed to investigate the potential protective effects of oleanolic acid (OA) administration against diabetic nephropathy considering biochemical and histopathological parameters. Materials and Methods: The rats with fasting blood glucose levels of 200 mg/dl and above were considered diabetic after induction of diabetes via injecting STZ. The other half of the rats were not injected with STZ (healthy rats). Both healthy and diabetic rats were then divided randomly into two subgroups to be administered with either OA (5 mg/kg) with 1 ml tap water by oral gavage or 1 ml tap water in the same route for 21 days. Serum urea-N, Ca, P, and Mg as well as renal tissue MDA, SOD, NF-κB, IL-6, IL-18, AMPK, YKL-40, and KIM-1 levels were measured. Results: OA administration partially decreased levels of serum urea-N and P, as well as levels of renal tissue MDA and inflammation markers (NF-κB, IL-6, IL-18, YKL-40, and KIM-1) in the diabetic rats. It also partially increased serum Ca and renal tissue AMPK levels in diabetic rats. These positive effects were also seen in renal tissue histopathology. Conclusion: OA treatment partially alleviated renal damage inflammatory and oxidative profiles in diabetic rats. [ABSTRACT FROM AUTHOR]

Comorbidities associated with obesity, including diabetes and kidney diseases, greatly increase mortality rates and healthcare costs in obese patients. Studies in animal models and clinical trials have demonstrated that L-serine supplementation is a safe and effective therapeutic approach that ameliorates the consequences of obesity. However, little is known about the effects of L-Serine supplementation following high-fat diet (HFD) consumption and its role in the mRNA expression of markers of kidney injury. We provide a descriptive action by which L-serine administration ameliorated the consequences of HFD consumption in relation to weight loss, glucose homeostasis as well as renal mRNA expression of markers of kidney injury. Our results indicated that L-Serine supplementation in drinking water (1%, ad libitum for 12 weeks) in male C57BL/6J mice promoted a significant reduction in body weight, visceral adipose mass (epididymal and retroperitoneal fat pads) as well as blood glucose levels in mice consuming a HFD. In addition, the amino acid significantly reduced the mRNA expression of the Kidney Injury Marker 1 (KIM-1), P2Y purinoceptor 1 (P2RY1), as well as pro-inflammatory cytokines (IL-6 and TNFα). L-serine administration had no effect on mice consuming a standard chow diet. Collectively, our findings suggest that L-serine is an effective compound for long-term use in animal models and that it ameliorates the metabolic consequences of HFD consumption and reduces the elevated levels of renal pro-inflammatory cytokines occurring in obesity.

In this study, we assessed the impact of commercially available polymyxin B against VRP-034 (novel formulation of polymyxin B) using a validated in vitro human renal model, aProximateTM. Freshly isolated primary proximal tubule cells (PTCs) were cultured in Transwell plates and treated with various concentrations of the formulations for up to 48 h. The functional expression of megalin–cubilin receptors in PTC monolayers was validated using FITC-conjugated albumin uptake assays. Polymyxin B and VRP-034 were evaluated at six concentrations (0.3, 1, 3, 10, 30, and 60 µM), and nephrotoxicity was assessed through measurements of transepithelial electrical resistance (TEER), intracellular adenosine triphosphate (ATP) levels, lactate dehydrogenase (LDH) release, and novel injury biomarkers [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and clusterin]. Additionally, histological analysis using annexin V apoptosis staining was performed. Our results indicated a significant decrease in TEER with polymyxin B at concentrations ≥10 μM compared to VRP-034. Toxic effects were observed from ATP and LDH release only at concentrations ≥30 μM for both formulations. Furthermore, injury biomarker release was higher with polymyxin B compared to VRP-034, particularly at concentrations ≥10 µM. Histologically, polymyxin B-treated PTCs showed increased apoptosis compared to VRP-034-treated cells. Overall, VRP-034 demonstrated improved tolerance in the aProximateTM model compared to polymyxin B, suggesting its potential as a safer alternative for renal protection.

The article discusses the findings of the Statin Therapy In Cardiac Surgery (STICS) trial, which investigated the effects of perioperative rosuvastatin on postoperative atrial fibrillation and cardiac injury in patients undergoing cardiac surgery. While rosuvastatin did not significantly affect these outcomes, it was unexpectedly associated with a higher incidence of acute kidney injury (AKI). Further analysis of the STICS samples revealed that rosuvastatin increased the risk of AKI and exacerbated renal proximal tubular injury. The study suggests that temporary perioperative statin cessation in patients undergoing cardiac surgery may be a reasonable option to consider. [Extracted from the article]

Rationale & Objective: Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established. Study Design: Prospective observational cohort. Setting & Participants: In the Atherosclerosis Risk in Communities) study, 948 participants were studied. Exposures: The baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998. Outcome: Incident CKD after 15 years of follow-up defined as ≥40% estimated glomerular filtration rate decline to

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and other symptoms which ultimately cause various other complications like retinopathy, micro angioplasty and nephropathy. piperine shows antidiabetic activity by improving insulin level, signifying its usage in the management of hyperglycemia. IGF-1 is the insulin-like growth factor receptor. KIM-1 has proved to be an outstanding early indicator of kidney injury in the rats. Induction of type 2 diabetes to male wistar albino rats, they were divided into four groups, one group were treated with piperine, fasting blood glucose was analysed. Biochemical analysis and mRNA expression analysis of KIM-1 and IGF-1 by RT-PCR is done. Fasting blood glucose and the serum insulin was elevated in diabetes induced rats. piperine-treated animals exhibited a significant decrease in the level of FBG and serum insulin from the above study, it could show that piperine possesses antidiabetic activity. [ABSTRACT FROM AUTHOR]