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Introduction: Pemetrexed is a key therapeutic agent for advanced non‐squamous non‐small cell lung cancer (Nsq‐NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq‐NSCLC treated with pemetrexed. Methods: We conducted a retrospective study including 136 patients with Nsq‐NSCLC treated with pemetrexed. Data on demographics, renal function, progression‐free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log‐rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. Results: The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Conclusion: Renal injury is a considerable complication in patients with Nsq‐NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Women with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments. Methods: Using timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments. Results: HELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival. Conclusion: HELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension. [ABSTRACT FROM AUTHOR]

To investigate the preventive effect of aerobic exercise on renal damage caused by obesity. The mice in the Control (Con) and Control + Exercise (Con + Ex) groups received a standard chow diet for the 21-week duration of the study, while the High-fat diet (HFD) group and High-fat diet + Exercise (HFD + Ex) group were fed an HFD. Mice were acclimated to the laboratory for 1 week, given 12 weeks of being on their respective diets, and then the Con + Ex and HFD + Ex groups were subjected to moderate intensity aerobic treadmill running 45 min/day, 5 days/week for 8 weeks. We found that HFD-induced obesity mainly impacts kidney glycerin phospholipids, glycerides, and fatty acyls, and aerobic exercise mainly impacts kidney glycerides, amino acids and organic acids as well as their derivatives. We identified 18 metabolites with significantly altered levels that appear to be involved in aerobic exercise mediated prevention of HFD-induced obesity and renal damage, half of which were amino acids and organic acids and their derivatives. Aerobic exercise rewires kidney metabolites to reduce high-fat diet-induced obesity and renal injury. [ABSTRACT FROM AUTHOR]

Introduction: The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction. Methods: Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline. Results: The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3–24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period. Conclusions: Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study. [ABSTRACT FROM AUTHOR]

Context: Obesity and pre-diabetes are associated with renal dysfunction via elevated oxidative stress. Peat moss, or Sphagnum cuspidatulum Müll. Hal., Sphagnaceae (SC), are rich in phenolic compounds that enhance antioxidant activity. Objective: SC might show beneficial effects in pre-diabetes-associated renal dysfunction. Materials and methods: Male Wistar rats, after 4 weeks on a high-fat diet, received low-dose streptozotocin to induce pre-diabetes. Then, the pre-diabetic rats were randomly divided into 4 groups: untreated pre-diabetic rats (P-DM), pre-diabetic rats treated with SC 50 or 100 mg/kg/day (P-DM50 or P-DM100), and pre-diabetic rats treated with metformin 100 mg/kg/day (MET). The drugs were fed by gavage for 4 weeks. Results: Treatment with SC100 dramatically lowered serum creatinine (S.Cr.), blood urea nitrogen (BUN), and augmented creatinine clearance in pre-diabetic rats. Additionally, SC100 significantly decreased the malondialdehyde level. Furthermore, pre-diabetic rats treated with SC100 significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream mediators, with downregulated apoptotic markers. Discussion and conclusion: Our findings provide a scientific basis for the clinical application of SC and a new strategy for the prevention of nephrotoxicity and other kidney disease in the future. [ABSTRACT FROM AUTHOR]

Aim: To describe treatment-induced toxicities (TITs) and associated factors in Zimbabwean cancer patients receiving cisplatin. Methods: In total, 252 Zimbabwean women with cervical cancer, receiving cisplatin were followed up over 12 months for TITs and disease status. Results: Peripheral neuropathy (70%) and ototoxicity (53%) were most prevalent. Advanced disease (OR = 1.3; 95% CI = 1.1–1.5; p = 0.02), pain comedications (OR = 1.3; 95% CI = 1.1–1.5; p = 0.03), alcohol (OR = 2.8; 95% CI = 1.1–7.5; p = 0.04) and comorbidities (OR = 1.2; 95% CI = 1.1–1.4; p = 0.04) increased peripheral neuropathy and ototoxicity risk. Older age increased risk of disease progression (OR = 1.9; 95% CI = 1.4–3.0; p = 0.033). Conclusion: High peripheral neuropathy and ototoxicity prevalence were observed, which are not routinely monitored in Zimbabwe. There is a need for capacity building to incorporate comprehensive TIT testing and optimize cancer care in Zimbabwe. Plain Language Summary Cancer treatment has side effects, also known as treatment-induced toxicities (TITs), that can lead to death if not management properly. African populations are more likely to develop TITs, however, not many studies research on TITs in Africans and why they are more prone to TITs. This study followed up 252 Zimbabwean women with cervical cancer, over 12 months for TITs and found that loss of sensation and ear complications most commonly occurred after treatment. Advanced disease, prescribed pain medication, alcohol consumption history and underlying diseases such as diabetes increased likelihood of TITs, while older age increased risk of unresponsive cancer. This study highlights a need to incorporate comprehensive monitoring for TITs for at-risk individuals toward improving cancer care. Article highlights Peripheral neuropathy and ototoxicity are common in Zimbabwean cancer patients, even though they are not routinely monitored in oncology facilities. Clinical factors such as comorbid conditions, pain co-medications and high cisplatin dose increase the risk of developing treatment-induced toxicities (TITs). High BMI was a predictor of peripheral neuropathy development. Lifestyle factors such as history of alcohol consumption can increase the risk of treatment-induced toxicities. In this study, HIV was not a risk factor for any of the TITs and treatment outcomes such as relapse, disease progression and mortality. Older patients are more prone to poor prognosis compared with younger patients highlighting a need for cancer screening even beyond the prescribed age of 40 years. Comprehensive TIT monitoring should be implemented in Zimbabwe primary care for cancer patients, to include peripheral neuropathy and ototoxicity, toward improving patient management. More studies to describe TITs in low-resource settings such as Zimbabwe are required in order to personalize medicine. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion injury (IRI) is unavoidable during kidney transplant and it is responsible for delayed or non-function after kidney transplantation. Cysteamine is the standard drug in the management of nephropathic cystinosis and its extra-renal complications. Thus, we designed this study to investigate its potential against renal reperfusion injury. Results: Significant elevation of H2O2, MDA, and nitrite and reduced GPx, GSH, and protein thiol in the Ischemia-reperfusion injury rats was reversed by cysteamine (50 and 100 mg/kg). Serum MPO, TNF-a, IL-1ß, creatinine, and AOPP were significantly elevated in IRI while rats treated with cysteamine revealed a significant decrease (p < 0.05) in the activities of these proinflammatory and renal injury markers. Conclusion: Based on its activity against inflammation, apoptosis, and free radical-induced stress, cysteamine has great potential to be used as a kidney transplant pre-operative drug to prevent renal reperfusion injury. [ABSTRACT FROM AUTHOR]

Objective(s): Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways. Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group. Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA’s preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism. Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones. [ABSTRACT FROM AUTHOR]

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial–mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Introduction Pemetrexed is a key therapeutic agent for advanced non‐squamous non‐small cell lung cancer (Nsq‐NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq‐NSCLC treated with pemetrexed. Methods We conducted a retrospective study including 136 patients with Nsq‐NSCLC treated with pemetrexed. Data on demographics, renal function, progression‐free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log‐rank test. The creatinine clearance rate (CCr) was calculated, and a CCr

Leptospirosis is caused by pathogenic leptospires, posing a significant public health problem. Host susceptibility to Leptospira infection is a multifactorial trait, and the host's genetic background can influence both the establishment of infection and the severity of the disease. Complement Factor H (FH) plays a crucial role in the interaction between pathogenic bacteria and the host. Genetic variants in the FH gene CFH have previously been associated with non-infectious diseases. Here, we aimed to analyze the effect of CFH variants on individual susceptibility to leptospirosis and disease severity. To accomplish this, we sequenced CFH exons 7, 9, 21, 22, and 23 in a case/control cohort (184/162) from two endemic leptospirosis areas in Brazil and Argentina. We identified twenty-one single nucleotide variants (SNVs). In the Brazilian cohort, the intronic variant rs34815383 exhibited a higher frequency in patients than in controls, resulting in a significant association with leptospirosis (p = 0.032; OR: 0.32; 95% CI 0.1–1) and also renal disorder (p = 0.001; OR: 5.3; 95%CI 1.8–15.57). This SNV is reported to be a splicing variant, negatively impacting CFH expression, and has previously been associated with Complement-driven renal disease. A second synonymous variant, rs61822181, was significantly less frequent in patients than in controls (p = 0.002; OR: 7.33; 95% CI 1.59–33.7), representing a protective factor against the development of leptospirosis. Our study represents the first documentation of the frequency of CFH SNVs in South America and identifies the variant rs34815383 T > C as a risk factor for leptospirosis and leptospirosis-related renal complications. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed. Results High fructose diet fed rats had increased plasma KIM-1, NGAL (p

In this study, Lactobacillus paracasei FP02, a strain isolated from pickled Chinese cabbage, was tested for its capability to reduce uric acid in vitro, and its physiological and biochemical characteristics were characterized. Furthermore, the effect of this strain on the serum uric acid level of a hyperuricemic (HUA) rat model was explored. The in vitro results showed that L. paracasei FP02 degraded uric acid and its precursor substances, inosine and guanosine, by 29.10%, 67.09%, and 70.48%, respectively, and inhibited xanthine oxidase (XOD) activity by 64.20%. Simultaneously, this strain could ferment various sugars (alcohols) and exhibited good tolerance to gastric acid and bile salts. The 14-day continuous intragastric administration of freeze-dried L. paracasei FP02 powder reduced the serum uric acid concentration by 49.96% compared to the hyperuricemia model group (P < 0.001), which was established by intragastric administration of potassium oxonate combined with high dietary uric acid. After the treatment, the serum uric acid concentration approached the levels observed in the blank control group. Additionally, in the FP02 treatment group, uric acid excretion in the urine increased, and serum XOD activity was significantly inhibited (P < 0.001). Renal sections showed that renal injury was partially restored in the FP02 treatment group. This study will lay the foundation for the development of L. paracasei FP02 as a potential drug or functional food for preventing HUA.

Abstract Background Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Abstract Background Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. Case presentation We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. Conclusions This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.

Objective To observe the inhibitory effects of tert-butylhydroquinone (tBHQ) on renal injury and oxidative stress and its regulatory effect on the nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-κB (NF-κB) signaling pathway in renal cortex and nucleus of rats with membranous nephropathy (MN), so as to illustrate the potential therapeutic effect and mechanism of tBHQ on MN. Methods Thirty-two rats were randomly divided into the normal control group, tBHQ control group, model group, and tBHQ intervention group, respectively. Rats in the normal control group were injected intraperitoneally with 3 mL of normal rabbit serum, rats in the tBHQ control group were injected with normal rabbit serum in the same way and then were gavaged with 50 mg/kg tBHQ once a day for a total of 15 injections, rats in the model group were injected intraperitoneally with 3 mL of rabbit Fx1A antiserum to establish passive Heymann nephritis (PHN) models, and rats in the tBHQ intervention group were injected with rabbit Fx1A antiserum in the same way and then were gavaged with 50 mg/kg tBHQ once a day for a total of 15 injections. At the end of the experiment, indicators related to nephrotic syndrome [24 h urinary protein (24 h-UPro) serum albumin (ALB), total cholesterol (T-CHOL), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)], renal function-related indicators [serum creatinine (sCr), urea nitrogen], renal podocyte injury (podocyte foot process fusion, glomerular Podocin/Desmin expression and distribution), renal cortex oxidative stress markers [malondialdehyde (MDA), 8-isoprostaglandin (8- iso-PG), 8-hydroxydeoxyguanosine (8-OHDG)], renal cortex antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), γ-glutamylcysteine synthase (γ-GCS)] activities and the Nrf2/NF-κB signaling pathway in the renal cortex and nucleus of the rats in each group were detected. Results Compared with the normal control group, the 24 h-UPro, T-CHOL, TG, HDL, LDL, sCr, and urea nitrogen increased, and ALB decreased (all P<0. 05); subepithelial electron dense deposits in the glomeruli, diffuse fusion of the podocyte foot processes, and the width of the podocyte foot processes increased; the expression level and abnormal distribution of Podocin decreased, the expression level of Desmin was up-regulated; the MDA, 8-iso-PG, and 8-OHDG levels all increased in the renal cortex (all P<0. 05), and the activities of SOD, CAT, and γ -GCS decreased (all P<0. 05); Nrf2 was down-regulated, whereas NF- κB p65 and p-NF- κB p65 (Ser536) were up-regulated in the renal cortex and nucleus in the model group (all P<0. 05). Compared with the model group, the 24 h-UPro, T-CHOL, TG, HDL, LDL, and sCr levels all decreased, and the ALB increased (all P<0. 05); the diffuse fusion of the podocyte foot processes was relieved, the podocyte foot processes width decreased, and the expression and distribution of Podocin/Desmin tended to be normal; the MDA, 8-iso-PG, and 8-OHDG levels decreased in the renal cortex (all P<0. 05), and the activities of SOD, CAT, and γ-GCS increased (all P<0. 05); Nrf2 was up-regulated, whereas NF-κB p65 and p-NF-κB p65 (Ser536) were down-regulated in the renal cortex and nucleus of the tBHQ intervention group (all P<0. 05). Conclusions The tBHQ inhibits renal injury and oxidative stress of MN rats, and can regulate the Nrf2/NF-κB signaling pathway in the renal cortex and nucleus. The tBHQ may activate Nrf2 and inhibit NF-κB activation, thereby alleviating oxidative stress and renal injury in MN rats. [ABSTRACT FROM AUTHOR]

AbstractCCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL. [ABSTRACT FROM AUTHOR]

Background: Evidence is sparse regarding the incidence or prevalence of renal or genitourinary injuries arising from contact sports. There are currently no World Health Organization or European consensus guidelines relating to the participation in sport for children and young athletes with a solitary (functioning) kidney. Purpose: To review the international literature and to make sport-specific recommendations for children and young athletes with a solitary (functioning) kidney participating in sports, based on the overall likelihood of potential renal or genitourinary injury. Study Design: Narrative review; Level of evidence, 4. Methods: A descriptive epidemiological study was conducted of current literature according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Embase, Google Scholar, Cochrane, and PubMed databases were queried from 1975 to 2023, to assess available evidence regarding the prevalence and risk of renal injury through sports participation and guidelines surrounding the participation in sports for children and young athletes with a solitary (functioning) kidney. Methodological quality and certainty of evidence were assessed according to the International Classification of Urological Disease guidelines. Results: A total of 28 publications were identified after database searches and exclusions, comprising 40,889 patients. The majority of papers providing recommendations arose from the United States. Of the recommendations, 79% permitted an unrestricted return to noncontact sports. A return to contact sports is permitted in most instances after physician consultation. Conclusion: There is a dearth of good-quality published evidence in the literature relating to sports participation with a solitary (functioning) kidney. Overall, the risk of genitourinary injury in sports is low, and after physician assessment, there is currently no strong evidence to exclude children and young athletes with a solitary (functioning) kidney from full participation in contact and collision sports. [ABSTRACT FROM AUTHOR]

chronic obstructive pulmonary disease (COPD), and to explore the mechanisms. METHODS: SPF-grade SD rats were randomly divided into control, COPD, pyrrolidinedithiocarbamate ammonium (PDTC), Bufei-Jianpi formula (BJF), Bu-fei-Yishen formula (BYF), Yiqi-Zishen formula (YZF), BJF combined with PDTC (BJF+PDTC), BYF combined PDTC (BYF+PDTC), and YZF combined PDTC (YZF+PDTC) groups. Cigarette smoke exposure combined with bacterial infection were used to develop a stable-phase rat model of COPD, and kidney-injured rats were screened for subsequent treatment. Pulmonary and renal functions, pathological changes in lung and kidney tissues, 24 h urine volume, urine biochemical indexes, aquaporin (AQP) levels, ratio of inflammatory cells in the bronchoalveolar lavage fluid (BALF), serum inflammatory factor levels, and mRNA and protein expressions of IκB kinase (IKK) and nuclear factor-κB (NF-κB) were observed at the end of the 16th week. RESULTS: Compared with control group, the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity (FVC), forced expiratory volume in 0. 1 second (FEV0.1 ) and FEV0.1/FVC (P<0. 05). The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration. The renal function indexes serum creatinine, blood urea nitrogen and serum cystatin C (Cys-C) were significantly increased (P<0. 01). The renal histopathology showed swollen and disorderly arranged tubular epithelial cells. The 24 h urine volume decreased (P<0. 01). The urinary biochemical indexes 24 h urinary total protein, urinary kidney injury molecule-1 (KIM-1), urinary Cys-C, and urinary N-acetyl-β-D-glucosaminidase significantly increased (P<0. 01). The protein levels of AQP1~4 were significantly incr eased (P<0. 01). The ratio of neutrophils and lymphocytes in the BALF were incr eased (P<0. 01). The ratio of monocytes was decr eased (P<0. 01). The serum levels of tumor necrosis factor-α (TNF-α), interleukin (lL)-6, IL-13, IL-1β, and transforming growth factor-β1 (TGF-β1) were significantly increased (P<0. 01). And the mRNA and protein expression levels of IKK, NF-κB were significantly elevated in the renal tissue (P <0. 05). Compared with COPD group, the above symptoms and indexes of the rats were improved to different degrees after the intervention in treatment groups, among which BJF, BYF and YZF demonstrated similar effects to PDTC, and BJF+ PDTC, BYF+PDTC and YZF+PDTC exhibited better improvements than the corresponding monotherapy. CONCLUSION : The three Tiao-Bu Fei-Shen therapies can reduce the airway and systemic inflammatory response, improve renal function and attenuate renal injury in COPD rats. The mechanism may be related to the inhibition of NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed. Results: High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman's capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function. Conclusions: β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury. [ABSTRACT FROM AUTHOR]

AIM: To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction (UUO), METHODS: Eight-week-old male C57BL/6J mice were divided into four groups randomly: sham group, UUO group, UUO+new dosage form of tadalafil (1 mg/kg) group and UUO+original patented drug of tadalafil (5 mg/kg) group. Surgery was performed to create a mouse UUO model, and therapeutic drugs were administered intragastrically for 7 d after modeling. A fully automated biochemi⁃ cal analyzer was used to detect serum creatinine (SCr) levels of each group. Through renal histopathological staining (HE staining, Masson trichrome staining, and immunohistochemistry staining) and Western blot, we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice, as well as its effect on the expression and distribution of fibronectin (FN) and α-smooth muscle actin (α-SMA), RESULTS: Compared with sham group, the SCr levels were significantly increased in mice with renal fibrosis, and renal tubules were dilated and infiltrated with inflammation. Moreover, the expressions of FN and α-SMA were increased significantly (P<0. 05), New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis, improved the renal tissue structure on the affected side, reduced collagen fiber deposition, and inhibited FN and α-SMA expression (P<0. 05), CONCLUSION: Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral obstruction. New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness. [ABSTRACT FROM AUTHOR]

Aim: Cisplatin is a highly effective anti‐cancer agent, but its clinical use is restricted due to severe renal toxicity. This study aimed to investigate the alleviative effects of juzentaihoto (JTT) in a mouse model of cisplatin‐induced renal injury. Methods: Four groups of seven‐week‐old male C57BL/6J mice (control, JTT, cisplatin, and JTT + cisplatin groups) were used in the study. The JTT and JTT + cisplatin groups received oral JTT (500 mg/kg) once a day for three days. After 24 h, the cisplatin, and JTT + cisplatin groups were intraperitoneally injected with cisplatin (15 mg/kg). The mice in each group were euthanized 72 h after cisplatin administration, and blood and kidney samples were collected. Results: Cisplatin injection decreased body weight and elevated plasma blood urea nitrogen and creatinine levels, while also increasing renal oxidative stress, inflammation, and cell death. These changes were alleviated by JTT administration. We also found that platinum accumulation in the kidneys following cisplatin injection was attenuated by JTT treatment. Furthermore, Mate1 expression levels (a cisplatin efflux transporter) were upregulated by JTT injection. Conclusion: Our results demonstrated that JTT mitigated cisplatin‐induced renal injury in mice by alleviating oxidative stress, inflammation, and cell death, achieved through the upregulation of the cisplatin efflux transporter Mate1. [ABSTRACT FROM AUTHOR]

Drug-induced kidney injury (DIKI) is a frequently reported adverse event, associated with acute kidney injury, chronic kidney disease, and end-stage renal failure. Prospective cohort studies on acute injuries suggest a frequency of around 14%–26% in adult populations and a significant concern in pediatrics with a frequency of 16% being attributed to a drug. In drug discovery and development, renal injury accounts for 8 and 9% of preclinical and clinical failures, respectively, impacting multiple therapeutic areas. Currently, the standard biomarkers for identifying DIKI are serum creatinine and blood urea nitrogen. However, both markers lack the sensitivity and specificity to detect nephrotoxicity prior to a significant loss of renal function. Consequently, there is a pressing need for the development of alternative methods to reliably predict drug-induced kidney injury (DIKI) in early drug discovery. In this article, we discuss various aspects of DIKI and how it is assessed in preclinical models and in the clinical setting, including the challenges posed by translating animal data to humans. We then examine the urinary biomarkers accepted by both the US Food and Drug Administration (FDA) and the European Medicines Agency for monitoring DIKI in preclinical studies and on a case-by-case basis in clinical trials. We also review new approach methodologies (NAMs) and how they may assist in developing novel biomarkers for DIKI that can be used earlier in drug discovery and development. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective: To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods: Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results: All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion: The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. Case presentation: We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient's renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. Conclusions: This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency. [ABSTRACT FROM AUTHOR]

Objective To investigate the serum levels of homocysteine(HCY)and cystatin C(Cys-C)in patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)associated renal injury, and to explore the diagnostic value of combined detection of HCY and Cys-C in ANCA-associated renal injury. Methods We selected 70 ANCA-positive patients with renal injury admitted to the Department of Nephrology in our hospital from January 2016 to January 2019. Another 48 patients with ANCA-positive but not complicated with renal injury were in simple ANCA positive group while 50 patients with physical examination who came to the hospital during the same period were in control group. Healthy patients served as the control group. By comparing the differences in the test results of different groups, the area under the curve(AUC)of each test index for ANCA-positive renal injury was determined, and the correlation and diagnostic value of combined detection of HCY and Cys-C for ANCA-related renal injury were calculated. Results The levels of HCY and Cys-C in the ANCA positive combined with renal injury group, the pure ANCA positive group, and the control group differed significantly(P<0.05). The positive rates of HCY and Cys-C in the two groups were significantly different(P<0.05). The sensitivity and specificity of HCY and Cys-C in combination for the diagnosis of ANCA-positive related renal injury were significantly higher than those of the above indicators alone(P<0.05). ROC curve results showed that HCY combined with Cys-C had a better diagnosis for patients with positive ANCA and associated renal injury and a higher correlation. Conclusion HCY combined with Cys-C is closely correlated to ANCA-related renal injury, and the combined detection has a positive effect on the diagnosis of patients with ANCA-positive related renal injury, and has guiding value for the treatment of patients. [ABSTRACT FROM AUTHOR]

With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless, epidemiological data on the health status of these preterm infants have begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in adulthood, affecting their quality of life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of the hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury. Key Points Premature infants commonly receive supplementary oxygen. Hyperoxia can cause kidney damage via signal pathways. We should reduce the occurrence of late sequelae. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) could lead to renal failure and its morbidity is increasing throughout the world. The activation of AMP-activated protein kinase (AMPK) has been proven to play a protective role in kidneys under diabetic conditions. Objective: The present study aimed to explore the protection of GSK621, an AMPK agonist, on high glucose (HG)-induced renal injury, and to establish the mechanisms underlying these effects. Results: Mouse podocytes (MPC5) were injured by HG stimulation, as revealed by decreased proliferation and increased apoptosis. The intervention of GSK621 significantly protected MPC5 cells from HG-induced damage. Mechanically, GSK621 effectively restored HG-impaired cellular autophagy in MPC5 cells. By using chloroquine (CQ), an autophagy inhibitor, the protection of GSK621 on the cell survival and apoptosis of HG-treated MPC5 cells was blocked. In the streptozotocin-induced DN mice model, GSK621 treatment effectively prevented renal injury as indicated by decreased extracellular matrix deposition and fibrotic lesions in the kidney. GSK621 also decreased urinary protein and albumin, fasting blood glucose, serum creatinine, as well as blood urea nitrogen levels. However, the administration of CQ could curtail these beneficial effects of GSK621. In addition, the autophagy was restored by GSK621 partly via regulating the AMPK/ULK1 pathway in the kidney of the DN mice model. Conclusion: Our findings revealed that GSK621 mitigates HG-induced renal injury by activating autophagy via the AMPK/ULK1 pathway in vitro and in vivo and, therefore, exerts a protective action on DN. GSK621 is a novel potential drug for DN. [ABSTRACT FROM AUTHOR]

This study used skipjack by-products to produce skipjack trypsin hydrolysate (STH), which was then processed through the Maillard reaction to create its Maillard product, STHMS3 (200–1000 Da). We evaluated STHMS3's protective effects against hyperuricemia-induced renal injury in mice. Utilizing in vivo experiments, network pharmacology, and molecular docking, we explored its protective mechanisms. STHMS3 significantly decreased serum uric acid, creatinine, blood urea nitrogen, and xanthine oxidase (XOD) levels, reduced oxidative stress, and enhanced antioxidant protein levels in kidneys. Network pharmacology analysis showed STHMS3's interaction with multiple targets and pathways, including apoptosis, NF-κB, and TNF signaling pathways, suggesting a multi-level interactive network mechanism. Molecular docking confirmed STHMS3's ability to directly inhibit XOD through hydrogen bond formation. This study highlights the therapeutic potential of food-derived peptides in managing hyperuricemia and protecting renal function.

Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.

Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause–effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients’ financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages ‘TwoSampleMR’ and ‘Mendelianrandomization’ to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73–0.96, p = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786–0.957, p = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010–0.437, p = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.

Purpose To investigate the preventive effect of aerobic exercise on renal damage caused by obesity.Methods The mice in the Control (Con) and Control + Exercise (Con + Ex) groups received a standard chow diet for the 21-week duration of the study, while the High-fat diet (HFD) group and High-fat diet + Exercise (HFD + Ex) group were fed an HFD. Mice were acclimated to the laboratory for 1 week, given 12 weeks of being on their respective diets, and then the Con + Ex and HFD + Ex groups were subjected to moderate intensity aerobic treadmill running 45 min/day, 5 days/week for 8 weeks.Results We found that HFD-induced obesity mainly impacts kidney glycerin phospholipids, glycerides, and fatty acyls, and aerobic exercise mainly impacts kidney glycerides, amino acids and organic acids as well as their derivatives. We identified 18 metabolites with significantly altered levels that appear to be involved in aerobic exercise mediated prevention of HFD-induced obesity and renal damage, half of which were amino acids and organic acids and their derivatives.Conclusion Aerobic exercise rewires kidney metabolites to reduce high-fat diet-induced obesity and renal injury.

ContextObesity and pre-diabetes are associated with renal dysfunction via elevated oxidative stress. Peat moss, or Sphagnum cuspidatulum Müll. Hal., Sphagnaceae (SC), are rich in phenolic compounds that enhance antioxidant activity.ObjectiveSC might show beneficial effects in pre-diabetes-associated renal dysfunction.Materials and methodsMale Wistar rats, after 4 weeks on a high-fat diet, received low-dose streptozotocin to induce pre-diabetes. Then, the pre-diabetic rats were randomly divided into 4 groups: untreated pre-diabetic rats (P-DM), pre-diabetic rats treated with SC 50 or 100 mg/kg/day (P-DM50 or P-DM100), and pre-diabetic rats treated with metformin 100 mg/kg/day (MET). The drugs were fed by gavage for 4 weeks.ResultsTreatment with SC100 dramatically lowered serum creatinine (S.Cr.), blood urea nitrogen (BUN), and augmented creatinine clearance in pre-diabetic rats. Additionally, SC100 significantly decreased the malondialdehyde level. Furthermore, pre-diabetic rats treated with SC100 significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream mediators, with downregulated apoptotic markers.Discussion and conclusionOur findings provide a scientific basis for the clinical application of SC and a new strategy for the prevention of nephrotoxicity and other kidney disease in the future.

Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1β, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury.

Background: The onset of obesity-associated renal injury is insidious and asymptomatic. Therefore, finding an early marker will be extremely useful in its detection. Kidney injury molecule-1 (KIM-1) can be evaluated as an early marker for renal injury in obese children. Methods: This case control study involved two groups: a case group of 45 Egyptian overweight/obese children and a control group of 45 non-obese peers. Anthropometry and blood pressure were measured in both groups. Additionally, KIM-1 and serum creatinine levels were assessed. Results: Compared to the control group, the case group showed a significantly higher systolic (P-value 0.000) and diastolic (P-value 0.002) blood pressure. A significantly higher serum creatinine (P=0.007) and KIM-1 (P=0.001) were also found. Conclusion: It is inferred that obesity impacts renal hemodynamics early in childhood. Thus, identifying a screening marker like KIM-1 is useful for the early diagnosis of renal injury.

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorlycontrolled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocytedamage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluatethe nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore theunderlying mechanism.Materials and Methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) toinduce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, andorgan weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levelswere determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the ratswere sacrificed and their renal tissues were removed for histopathological assessment.Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepaticweights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine(Cr) and, albumin. There was a decrease (P

Abstract Background The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. Results A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3−/−) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. Conclusion Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract Graphical Abstract

Congenital solitary functioning kidney (cSFK) is one of the major causes of chronic kidney disease (CKD) in children. Long-term renal hyperfiltration leads to kidney injury with hypertension, proteinuria and lower estimated glomerular filtration rate (eGFR). Early clinical manifestations of cSFK children are generally insignificant. They are more prone to develop kidney injury then progress to end-stage renal disease. Long-term managements and aggressive interventions should be implemented for better outcomes. The pathogenesis, pathophysiological rationales of renal injury, clinical manifestations and proper managements of cSFK were summarized.

BackgroundThe burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. ObjectiveTo preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. MethodsA mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. ResultsThe mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P0.05), but the renal histopathological injury scores were significantly increased (P0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P

We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99 m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease. [ABSTRACT FROM AUTHOR]

Hydronephrosis resulting from unilateral ureteral obstruction (UUO) is a common cause of renal injury, often progressing to late-stage renal fibrosis or even potential renal failure. Renal injury and repair processes are accompanied by changes in cellular senescence phenotypes. However, the mechanism is poorly understood. The purpose of this study is to clarify the changes in senescence phenotype at different time points in renal disease caused by UUO and to further investigate whether eliminating senescent cells using the anti-senescence drug ABT263 could attenuate UUO-induced renal disease. Specifically, renal tissues were collected from established UUO rat models on days 1, 2, 7, and 14. The extent of renal tissue injury and fibrosis in rats was assessed using histological examination, serum creatinine, and blood urea nitrogen levels. The apoptotic and proliferative capacities of renal tissues and phenotypic changes in cellular senescence were evaluated. After the intervention of the anti-senescence drug ABT263, the cellular senescence as well as tissue damage changes were re-assessed. We found that before the drug intervention, the UUO rats showed significantly declined renal function, accompanied by renal tubular injury, increased inflammatory response, and oxidative stress, alongside aggravated cellular senescence. Meanwhile, after the treatment with ABT263, the rats had a significantly lower number of senescent cells, attenuated renal tubular injury and apoptosis, enhanced proliferation, reduced oxidative stress and inflammation, improved renal function, and markedly inhibited fibrosis. This suggests that the use of the anti-senescence drug ABT263 to eliminate senescent cells can effectively attenuate UUO-induced renal injury. This highlights the critical role of cellular senescence in the transformation of acute injury into chronic fibrosis. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds in managing CKD and its complications. By examining the existing research, we highlight their diverse biological activities and potential to combat CKD-related issues. We analyze the nutritional benefits, bioavailability, and safety profile of these compounds. While the clinical evidence is promising, preclinical studies offer valuable insights into underlying mechanisms, optimal dosages, and potential side effects. Further research is crucial to validate the therapeutic efficacy of phenolic compounds for CKD. We advocate for continued exploration of their innovative applications in food, pharmaceuticals, and nutraceuticals. This review aims to catalyze the scientific community's efforts to leverage phenolic compounds against CKD-related challenges. [ABSTRACT FROM AUTHOR]

High-fat diets (HFDs) and sedentary lifestyles are associated with obesity, a significant global health issue that affects over 30% of people in industrialized countries. It is associated with metabolic syndrome, type 2 diabetes, high cholesterol levels, and abnormal lipid metabolism. High-fructose diets can lead to type 2 diabetes, insulin resistance, and inflammation in fat tissue. Statins, particularly hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been used to treat obesity and diabetes, but their impact on kidney damage in obese rats is limited. This research aimed to investigate the impact of atorvastatin on renal damage resulting from a high-fat, high-fructose diet (HF-HFrD) in rats. This study involved 24 adult male Sprague Dawley rats, divided into four groups: the control group, the atorvastatin (Ator) group, the high-fat-high-fructose diet (HF-HFr) group, and the high-fat-high-fructose diet with atorvastatin (HF-HFr + Ator) group. Rats were anesthetized, weighed, and sacrificed, and blood was collected from the abdominal aorta and kidneys. Biochemical studies were performed to detect serum urea, creatinine, glucose, insulin, lipid profile, malondialdehyde (MDA) levels, and reduced glutathione (GSH) activity. The histopathological evaluation included H&E, Sirius red staining, NF-κB, and caspase-3 immunohistochemical staining. The HFHFrD group had elevated levels of serum glucose, insulin, HOMA-IR, creatinine, BUN, cholesterol, and triglycerides while showing a reduction in HDL. The renal tissue exhibited increased levels of MDA, decreased levels of GSH, higher collagen accumulation, and increased expression of NF-κB and caspase-3. Atorvastatin therapy effectively improved these alterations in comparison to the HF-HFrD group. In conclusion, atorvastatin improved HF-HFrD-induced renal injury by modulating lipotoxicity, oxidative stress, inflammation, and apoptosis. Atorvastatin may have therapeutic potential for obesity-related kidney damage. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) is the most commonly used diagnostic modality for blunt abdominal trauma (BAT), significantly influencing management approaches. Deep learning models (DLMs) have shown great promise in enhancing various aspects of clinical practice. There is limited literature available on the use of DLMs specifically for trauma image evaluation. In this study, we developed a DLM aimed at detecting solid organ injuries to assist medical professionals in rapidly identifying life-threatening injuries. The study enrolled patients from a single trauma center who received abdominal CT scans between 2008 and 2017. Patients with spleen, liver, or kidney injury were categorized as the solid organ injury group, while others were considered negative cases. Only images acquired from the trauma center were enrolled. A subset of images acquired in the last year was designated as the test set, and the remaining images were utilized to train and validate the detection models. The performance of each model was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value based on the best Youden index operating point. The study developed the models using 1302 (87%) scans for training and tested them on 194 (13%) scans. The spleen injury model demonstrated an accuracy of 0.938 and a specificity of 0.952. The accuracy and specificity of the liver injury model were reported as 0.820 and 0.847, respectively. The kidney injury model showed an accuracy of 0.959 and a specificity of 0.989. We developed a DLM that can automate the detection of solid organ injuries by abdominal CT scans with acceptable diagnostic accuracy. It cannot replace the role of clinicians, but we can expect it to be a potential tool to accelerate the process of therapeutic decisions for trauma care. [ABSTRACT FROM AUTHOR]