Indices Of Renal Function Research Articles

The influence of intermittent venovenous hemodiafiltration on the course of acute kidney injury in multiple trauma victims

Background. Acute kidney injury (AKI) is a common complication of polytrauma that requires renal replacement therapy (RRT) in 10 to 28 % of cases. RRT methods can be divided into discrete, or intermittent, and continuous. There are currently no clear recommendations regarding the choice of the RRT method. The purpose was to study the effect of intermittent venovenous hemodiafiltration (HDF) on indicators of renal function, hemodynamics, homeostasis and inflammation in multiple trauma victims with rhabdomyolysis and AKI. Materials and methods. Fifty victims with multiple trauma complicated by rhabdomyolysis and AKI were examined. We investigated the levels of total creatine kinase and myoglobin, indicators of kidney function, frequency of vasopressor support, indicators of general blood analysis, liver complex, coagulogram, acid-base and gas composition of blood. The study was conducted upon admission, before the start and after the end of each HDF session and on the last day of treatment. Results. Multiple trauma with massive rhabdomyolysis led to AKI, manifested by oliguria and hyperazotemia (and from the 3rd day, by hyperkalemia), as well as cardiovascular failure, anemia, liver dysfunction, and inflammatory response. AKI progression to renal failure despite conservative therapy led to the beginning of HDF on 3.6 ± 0.8 days of hospital stay. HDF allowed to effectively reduce indicators of the renal complex and normalize the potassium level, and at the same time did not have a negative effect on hemostasis or other indicators of homeostasis. 72.9 % of victims needed two HDF sessions, 47.9 % — three, 31.3 % — four or more. The most pronounced reduction of hyperazotemia was observed after the second session. Among the survivors, restoration of adequate diuresis by the day 14 was observed in 39.3 % of cases. The mortality rate was 34.0 %. Laboratory markers of renal function were not significantly different between survivors and deceased; the difference was in markers of liver function, coagulogram and acid-base balance, as well as the need for vasopressor support. That is, the mortality was due to the progression not so much of kidney failure, but of the failure of other organs and systems. It should also be noted that the injury severity score among survivors was 23.5 ± 4.0 points, and among non-survivors — 40.5 ± 6.8 points (p < 0.001). Conclusions. Multiple trauma with massive rhabdomyolysis leads to the development of multiple organ failure. Intermittent HDF allows to quickly and effectively reduce azotemia and normalize potassium levels without adversely affecting coagulation or other indicators of homeostasis. Most multiple trauma victims need 2 or more sessions of HDF. Mortality remains high and primarily depends on the severity of anatomical injuries and the addition of other organs and systems failure.

PM2.5 Exposure Induces Glomerular Hyperfiltration in Mice in a Gender-Dependent Manner

As one of the most common air pollutants, fine particulate matter (PM2.5) increases the risk of diseases in various systems, including the urinary system. In the present study, we exposed male and female C57BL/6J mice to PM2.5 for 8 weeks. Examination of renal function indices, including creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), and urinary microalbumin, indicated that the kidneys of female mice, not male mice, underwent early renal injury, exhibiting glomerular hyperfiltration. Meanwhile, pathological staining showed that the kidneys of female mice exhibited enlarged glomerulus that filled the entire Bowman’s capsule in the female mice. Afterward, we explored the potential causes and mechanisms of glomerular hyperfiltration. Variations in mRNA levels of key genes involved in the renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) demonstrated that PM2.5 led to elevated glomerular capillary hydrostatic pressure in female mice by disturbing the balance between the RAS and KKS, which in turn increased the glomerular filtration rate (GFR). In addition, we found that PM2.5 increased blood glucose levels in the females, which enhanced tubular reabsorption of glucose, attenuated macular dense sensory signaling, induced renal hypoxia, and affected adenosine triphosphate (ATP) synthesis, thus attenuating tubuloglomerular feedback (TGF)-induced afferent arteriolar constriction and leading to glomerular hyperfiltration. In conclusion, this study indicated that PM2.5 induced glomerular hyperfiltration in female mice by affecting RAS/KKS imbalances, as well as the regulation of TGF; innovatively unveiled the association between PM2.5 subchronic exposure and early kidney injury and its gender dependence; enriched the toxicological evidence of PM2.5 and confirmed the importance of reducing ambient PM2.5 concentrations.

Evaluation of renal oxygenation and perfusion in patients with chronic kidney disease: a preliminary prospective study based on functional magnetic resonance

Background Renal hypoxia and ischemia significantly contribute to chronic kidney disease (CKD) progression, underscoring the need for noninvasive quantitative assessments. This study employs blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) and arterial spin labeling (ASL) MRI to comprehensively evaluate renal oxygenation and blood flow in CKD patients. Methods Forty-two CKD patients across stages 1–5 and ten healthy volunteers underwent simultaneous BOLD-MRI and ASL-MRI. We measured oxygenation (T2* values) and renal blood flow (RBF) in both the renal cortex and medulla, assessing their correlations with estimated glomerular filtration rate (eGFR) and other renal function indicators. Results BOLD and ASL revealed higher oxygenation and RBF in the renal cortex than in the medulla. Across CKD stages 2–5, both cortical and medullary oxygenation levels, as well as RBF, were lower than those in the control group and progressively decreased with CKD advancement. Additionally, renal oxygenation and blood flow levels positively correlated with serum creatinine (SCr), cystatin C (Cys C), and blood urea nitrogen (BUN), and negatively correlated with estimated glomerular filtration rate (eGFR) (p < 0.001). However, no significant correlation was observed with uric acid (UA) (p > 0.05). Notably, patients with CKD stages 1–3 exhibited strong correlations between renal oxygenation levels, RBF, and eGFR, while those with CKD stages 4–5 displayed weak correlations. Conclusion BOLD-MRI and ASL-MRI effectively measure renal oxygenation and perfusion noninvasively, confirming their utility in tracking CKD progression. These modalities provide accurate assessments of renal function and hypoxic-ischemic injuries across CKD stages, particularly in the early stages.

Association between serum neurofilament light chain levels and chronic kidney disease: a cross-sectional population-based study from the National Health and Nutrition Examination Survey (2013–2014 cycle)

Background The relationships of serum neurofilament light chain (NfL) levels with chronic kidney disease (CKD) and renal function indicators remain controversial, and comprehensive studies with large sample sizes are lacking. Methods In total, 2,051 participants aged 20 to 75 years were identified from the National Health and Nutrition Examination Survey (2013-2014 cycle). Logistic regression models were used to assess the associations between serum NfL levels and CKD, whereas multivariate linear models were used to investigate the relationships between serum NfL levels and two kidney function indicators, namely, estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR). Adjustments were made to account for potential confounding variables in the analysis. Subgroup analyses stratified by age and sex were conducted. When sNfL is incorporated into the model as continuous variables, a log transformation is applied. Results The present study included a cohort of 2,051 individuals ranging in age from 20 to 75 years. After covariate adjustment, multivariable logistic regression revealed a significant association between high serum NfL levels and an increased prevalence of CKD (OR 1.60; 95% CI 1.40–1.82; p < 0.0001), which remained significant when analyzed by quartiles (p for trend <0.0001). There was a statistically significant inverse correlation between the serum NfL level and the eGFR (β=-6.34; 95% CI −8.32 to −4.37; p < 0.0001), as well as a positive correlation between the serum NfL level and the UACR (β = 84.67; 95% CI 19.52-149.83; p < 0.0001). Furthermore, when stratified by age, there were significant interactions of serum NfL levels with CKD, the eGFR, and the UACR (p for interaction = 0.008, 0.016, and 0.020, respectively). Conclusion Serum NfL levels are positively associated with the prevalence of CKD and the UACR but negatively correlated with the eGFR, particularly in older patients.

Rhabdomyolysis After Prolonged Tourniquet Application Is Associated with Reversible Acute Kidney Injury (AKI) in Rats.

Extremity trauma, including ischemia (e.g., prolonged tourniquet application or crush), is common among battlefield injuries. Injured muscle releases toxins leading to rhabdomyolysis and, potentially, acute kidney injury (AKI). The goal of this study was to characterize sequelae of ischemic extremity injury over 72 h, focusing on time courses of rhabdomyolysis and AKI. Male Sprague Dawley rats were placed into two groups. Ischemic injury was produced in anesthetized rats using bilateral tourniquets (TK; n = 10) for 5 h; control (CON; n = 9) rats were treated identically without TK application. Indicators of rhabdomyolysis and renal function were measured in conscious rats 1 day preinjury (baseline, BL) and then at 1.5, 24, 48, and 72 h post-TK release. Prolonged TK application produced necrosis in both muscle and bone marrow but not in kidney. The wet/dry weights indicated edema in injured limbs at 72 h (4.1 (0.5) (TK) vs. 2.9 (0.1) (CON); p < 0.001). TK rats exhibited a 100-fold increase in creatine kinase activity compared to CON at 1.5 h (20,040 (7265) U/L vs. 195 (86) U/L (mean (SD); p < 0.0001). TK decreased the mean glomerular filtration rate (GFR; p < 0.001) at 1.5 h, but these values recovered by 24 h in concert with elevated urinary flow and alkalinization. Prolonged ischemic extremity injury therefore produced severe rhabdomyolysis without irreversible renal damage.

Abstract 4137913: Role of serial evaluation of myocardial inflammatory activity and oxidative stress in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis

Background: Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis. Hypothesis: We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy. Aims: We identified prognostic markers for MACE in patients with CS after steroid therapy. Methods: This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of 18 F-FDG in heart were treated with steroids with standard guideline-recommended protocol. 18 F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation. Results: Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG &lt;11.6 ng/mg Cr and SUV max &lt;4.64 after steroid therapy indicate the good responses to the immunosuppressive therapy and better prognosis (Fig.3). Conclusion: U-8-OHdG and SUV max may be useful markers in determining the therapeutic efficacy and clinical outcome in patients with CS.

Vancomycin-induced acute kidney injury in rats: beneficial effects deriving from the co-administration of tadalafil or vitamin C

Background: Vancomycin (VAN) is widely employed in clinical settings for the treatment of severe infections attributable to multi-resistant bacteria, with a notable emphasis on Gram-positive strains. However, its therapeutic usage is significantly hampered by the potential for acute kidney injury (AKI); specifically, the nephrotoxic effects it can exert. In controlled experimental studies, the intraperitoneal (i.p.) administration of VAN at a dose of 400 mg/kg/day over a consecutive seven-day period has been shown to induce considerable AKI in rats. In addressing this concern, vitamin C (VC), recognized traditionally for its antioxidant properties, has been utilized to mitigate various forms of organ damage and inflammatory responses, primarily by diminishing oxidative stress and attenuating inflammation. Concurrently, tadalafil (TAD), a phosphodiesterase type-5 inhibitor commonly associated with the treatment of erectile dysfunction, is also noted for its beneficial anti-inflammatory and antioxidant effects, alongside vasodilatory properties. Aim: This study was designed in order to investigate the protective capabilities of TAD or VC against the VAN-induced nephrotoxic effects in a rat model of AKI. Methodology: A total of 24 male albino Wistar rats were allocated into four distinct groups for the purpose of comparative analysis. Following treatment, both kidney and blood samples were obtained for further evaluation. The study randomized the rats into four categories: group 1 served as the control group, group 2 received VAN at a dosage of 400 mg/kg (via an i.p. injection on a daily basis), group 3 was administered VAN (400 mg/kg; i.p., daily) in conjunction with TAD at a dose of 5 mg/kg daily, and group 4 was given VAN (400 mg/kg; i.p., daily) alongside VC at a dosage of 200 mg/kg daily. Results: Evaluations included the measurement of renal function indicators such as the serum levels of urea, of creatinine, and the creatinine clearance. Additionally, the analysis involved the assessment of antioxidant markers in renal tissue homogenates, including malondialdehyde (MDA), glutathione, and superoxide dismutase. To further elucidate the inflammatory response, indices such as the levels of the tumor necrosis factor-alpha, the interleukins (IL)-1β and IL-6, and the nuclear factor-κB were evaluated within the renal tissue homogenate samples of the studied rats. The administration of VAN resulted in a marked elevation of renal biomarkers and inflammatory indices, alongside a significant reduction in antioxidant levels, with an exception for MDA (which exhibited increased levels); these changes reached statistical significance (p&lt;0.05) when measured against the control group. In contrast, the supplementation with TAD or VC was effective in significantly lowering the serum levels of both renal and inflammatory indicators when compared to the group treated solely with VAN. Furthermore, antioxidant measurements improved, alongside a reduction in MDA levels, thereby demonstrating significant differences (p&lt;0.05). Conclusion: The findings of this study reveal that both TAD and VC provide a degree of renal protection against the VAN-induced damage by enhancing kidney function markers and, concurrently, lessening oxidative stress and inflammatory responses associated with nephrotoxicity.

Correlation between Fundus Damage and Renal Function Deterioration in Chronic Kidney Disease Patients.

This study aimed to explore the correlation between the extent of fundus damage and the severity strategies for chronic kidney disease (CKD). We collected data from 118 CKD patients, including general information, renal function indicators, and fundoscopic examination results. The stages of CKD and degrees of fundus lesions were graded. SPSS 25.0 software facilitated the analysis of correlations using Kendall's tau-b correlation analysis and ordinal regression analysis. Statistically significant differences were observed among multiple CKD stages in the distribution of age, systolic blood pressure, diastolic blood pressure, hemoglobin, total cholesterol, homocysteine, cystatin C, serum creatinine, blood urea, eGFR, 24-hour urine protein, urine microalbumin, urine microalbumin/urine creatinine, and blood β2 microglobulin, complement C3. Notably, the levels of cytokeratin 19 fragment and transforming growth factor β significantly increased in all CKD stages. Kendall's tau-b correlation analysis revealed a significant positive correlation between CKD stage and fundus lesion grade. Ordinal regression analysis indicated that sex differences, total cholesterol levels, and hemoglobin levels were significant predictors of fundus lesion risk. Compared with patients at stage 5 CKD, the risk of fundus damage significantly lower in patients in stage 2 and stage 3, further demonstrating a positive correlation between renal function deterioration and increased risk of fundus damage. Routine fundus screening and early intervention for fundus lesions are vital for assessing CKD deterioration, providing new directions for future related research.

Siling decoction ameliorates adenine-induced renal fibrosis in rats by the AKT/IKKβ/NFκB signaling pathway

ObjectiveInvestigating how Siling decoction (SLD) mitigates fibrosis in rats with chronic kidney disease CKD (chronic kidney disease) through network pharmacology analysis and experimental verification. MethodsInitially, the primary active components and their target actions of SLD (Fuling, Zhuling, Zexie, and Baizhu) were identified by the TCMSP database and liquid chromatography mass spectrometry (LC-MS). Treatment targets for renal fibrosis were screened through databases such as GeneCard, OMIM, PharmGkb, and GEO. Subsequently, a drug-disease-target network was constructed and subjected to PPI analysis. Intersecting targets underwent GO and KEGG pathway enrichment analyses. Renal fibrosis model was induced by adenine gavage, then treat with SLD. Masson, Sirius red, immunohistochemistry, and Western blot were used to detect renal function and fibrosis-related indicators. The mechanism was further validated in vitro experiments. ResultsNetwork pharmacology analysis identified 100 common targets associated with the active components of SLD, including core genes such as AKT1 and CCND1. GO enrichment analysis revealed that the top three biological processes impacted include response to xenobiotic stimulus, response to nutrient levels and response to oxidative stress. These processes involved cellular components such as membrane raft, membrane microdomain and synaptic membrane, with molecular functions predominantly associated with ubiquitin-like protein ligase binding, ubiquitin protein ligase binding, DNA-binding transcription factor binding, and RNA polymerase II-specific DNA binding transcription factor binding. KEGG pathway enrichment analysis indicated potential involvement of pathways like Lipid and atherosclerosis, PI3K-AKT signaling pathway, and prostate cancer are likely involved in the anti-fibrotic effect of SLD. Notably, the highlighted was the AKT/IKKβ/NFκB signaling pathway as a key mechanism. These findings were further confirmed in vivo and in vitro. ConclusionThe SLD effectively ameliorates adenine-induced chronic kidney disease fibrosis in rats, potentially by inhibiting the AKT/IKKβ/NFκB signaling pathway.

Correlation Between Renal Dimensions and Anthropometric Indices Using Computed Tomography in Adults Without Known Renal Disease: A Cross-Sectional Prospective Study

Background: Assessing renal volume as a potential indicator of renal function and related disorders is valuable for clinical decision-making. Computed tomography (CT) can accurately estimate actual kidney size. Objectives: This study aimed to evaluate the relationship between anthropometric parameters and renal dimensions measured by CT. Methods: Renal CT scan evaluations were performed on 634 individuals (308 males and 326 females) who had undergone abdominopelvic CT scans for indications unrelated to renal disease. Renal parameters, including length, width, depth, volume, and cortex length, were measured. Results: The mean age of participants was 53.5 ± 13.7 years (range: 18 - 86 years). Renal dimensions in males were larger than those in females. Additionally, the left kidney showed larger dimensions than the right kidney in both genders. Renal dimensions increased with age initially, but began to decrease after the sixth decade of life. A significant negative correlation was found between age and renal length, cortex, and left renal volume. In contrast, a significant positive correlation was observed between weight and both renal depth, length, volume, and left renal cortex, as well as between height and both renal length and volume on both sides. All dimensions except renal length were greater with increasing Body Mass Index (BMI). Conclusions: The results indicate a significant correlation between kidney dimensions and various anthropometric factors such as age, weight, height, and BMI. These findings provide valuable insights into kidney dimensions measured on CT scans, potentially aiding in the diagnosis and treatment of kidney diseases.

The relationship between serum uric acid and homocysteine is influenced by kidney function

Background and AimPrior research has established a relationship between homocysteine (Hcy) and serum uric acid (SUA) levels; however, the precise mechanisms underlying this association remain unclear. The objective of this research was to explore the correlation between SUA and Hcy and to evaluate the possible role of kidney function as a mediator in the connection between SUA and Hcy. Methods and ResultsConsecutive enrollment of 16870 participants aged 20-60 years was conducted at the Third Xiangya Hospital of Central South University. Self-reported health questionnaires were used to gather information on health behaviors and medical backgrounds. Trained personnel performed laboratory examinations using standard methods. A mediation analysis was performed to explore the possible effect of renal function on the association between SUA and Hcy levels. Estimated glomerular filtration rate (eGFR) was used to assess kidney function. Logistic regression analysis showed that SUA levels were positively correlated with Hcy levels and hyperhomocysteinemia (HHcy) risk (p<0.01). Subgroup analysis showed the robustness of the results. Significant mediation effects of eGFR were found in the relationship between SUA and Hcy, as demonstrated by the subsequent mediation analysis. In the overall study group, the percentage of eGFR mediated in the association between SUA and Hcy was 63.36%, with 41.59% and 57.59% in women and men, respectively. ConclusionsSUA was positively correlated with Hcy and HHcy risks, and the effects of SUA on Hcy may be mediated by renal function indicators (eGFR).

Establishment and validation of a population pharmacokinetic model for apatinib in patients with tumors

ObjectiveThis study aimed to develop a population pharmacokinetic (PPK) model for oral apatinib in Chinese oncology patients and investigate the factors influencing the pharmacokinetics of apatinib.MethodsWe gathered 199 blood concentration monitoring data points from 91 inpatient oncology participants receiving oral apatinib at the Third Affiliated Hospital of Soochow University. Covariates, such as age, gender, body weight, and indices of liver and renal function, were examined to assess their influence on the pharmacokinetic parameters of apatinib. The PPK model was developed using the nonlinear mixed-effects modeling procedure (NONMEM), and model validation was conducted using the bootstrap method and normalized prediction distribution error (NPDE) method.ResultsThe structural model adopted a one-compartment structure with first-order elimination. Notably, aspartate aminotransferase (AST) and the co-administered drug type emerged as primary covariates affecting apatinib clearance (CL/F). The finalized model was expressed as CL/F (L/h) = 56.7 × (AST/26.6)−0.298 × θ, when apatinib was combined with monoclonal antibodies, θ was 1; when combined with paclitaxel, θ was 0.58; when combined with other drugs (e.g., platinum, capecitabine, or the combination of tegafur, gimeracil, and oteracil potassium), θ was 1.60; When used as monotherapy, θ was 1.38. V/F = 674 L, and the absorption rate constant (Ka) was fixed at 0.08 h−1. Bootstrap results affirmed the model’s reliability and stability, while NPDE outcomes attested to the model’s fit.ConclusionOur study successfully established a PPK model for apatinib in oncology patients, revealing that liver function status and co-administered drug types significantly impacted apatinib CL/F. This finding underscored the potential necessity for dose adjustments to optimize efficacy, particularly in patients undergoing different chemotherapy regimens involving apatinib.

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- &amp; non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV &amp; non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV &amp; non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Elevation of circulating FGF23 in chronic kidney disease promotes atrial fibrosis through the AKT pathway

Abstract Background The relationship between chronic kidney disease (CKD) and atrial fibrillation (AF) remains unclear. Elevated level of fibroblast growth factor 23 (FGF23) is highly associated with increased cardiovascular disease and mortality in patients suffering from CKD. In recent years, studies have shown that FGF23 promotes cardiac hypertrophy through FGFR4, suggesting that FGF23 may be an important bridge between the heart and kidney. Purpose In this study, we sought to use a well-established rat model of CKD to further characterize the effects of CKD on AF and to identify potential drivers of CKD-induced AF. Methods 14 SD rats were randomly selected to undergo 5/6 nephrectomy and fed for 15 weeks to establish a CKD model, while the SHAM group (8 rats) underwent the same surgery without removing kidney tissue. Body weight, blood pressure, renal function, cardiac ultrasound, epicardial electrocardiography, and pathological indices were monitored in both groups. Gene sequencing was performed on the left atria to search for differentially expressed genes. Rat atrial fibroblasts were selected for further mechanism exploration. We chose TGF-β to stimulate fibroblasts to mimic the process of fibrosis in vivo, and then administered FGFR inhibitors to explore the downstream molecular mechanisms. Results Systolic blood pressure and creatinine were elevated in the CKD group. Compared with the SHAM group, the incidence of AF was significantly higher, left atrial diameter was significantly larger, and epicardial electrical markers showed that left atrial electrical conduction velocity was significantly slower and conduction heterogeneity was significantly increased in the CKD group. Pathologic staining of the left atrium showed significant fibrosis in the CKD group. Consistent with previous findings, FGF23 was significantly elevated in CKD rats. Transcriptomic sequencing revealed that FGFR4 expression was significantly upregulated in the left atrium of CKD rats, The results in rat atrial fibroblasts showed that blocking FGFR4 expression inhibited TGF-β-induced fibrosis and was mediated by the AKT pathway. Conclusions The mechanism of CKD-induced AF is that CKD promotes both structural and electrical remodeling of the atria. Further investigation of its possible downstream molecules revealed that elevated FGF23 in the CKD circulation promotes the development of atrial fibrosis by binding to FGFR4 through the AKT pathway.

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

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

Hypoglycemia and Hypolipidemia Assisted Nephroprotective Potential of Hygrophila auriculata (K. Schum) Heine in Streptozotocin/Nicotinamide Rodent Model of Type 2 Diabetes

The investigation was aimed at testing the nephroprotective potential of methanol extract (MEHA) from Hygrophila auriculata (K. Schum) Heine against hyperglycemia and dyslipidemia in adult Wistar albino rats with streptozotocin (STZ)/ nicotinamide (NA)-induced diabetic kidney disease (DKD). Adult male albino Wistar rats with fasting blood glucose (FBG) levels greater than 250 mg/dL were selected and randomly assigned to six groups after the induction of diabetes. The normoglycemic group (Group I) received oral saline, while diabetic groups (II-VI) received saline, MEHA at doses of 100, 200, and 400 mg/kg, and metformin (MET) at 180 mg/kg, respectively. MEHA and MET were administered orally as a 1% carboxymethyl cellulose (CMC) suspension from the 5th to the 8th week after diabetes induction. At week 8, comprehensive assessments were conducted to evaluate renal function, glycemic control, dyslipidemia, oxidative stress markers, and kidney histoarchitecture. MEHA treatment at 200 and 400 mg/kg and metformin demonstrated significant reductions in hyperglycemia, dyslipidemia, and oxidative stress. Furthermore, improved renal function indices and reduced vacuolar degeneration in renal tubules was seen in diabetic rats following MEHA and MET administration. The present study provides compelling evidence for the renoprotective efficacy of MEHA against STZ/NA-induced DKD in rats. This effect is likely attributed to MEHA's hypoglycemic, hypolipidemic, and antioxidant properties.

Value of Maternal Renal Function Indicators in Predicting Small for Gestational Age Infants in Patient with Severe Preeclampsia

Background: Severe preeclampsia poses significant health risks to both pregnant patients and their newborns. Our goal was to explore the association between serum renal function related indicators in pregnant patients with severe preeclampsia and the occurrence of small for gestational age (SGA) infants, as well as to further identify independent risk factors for SGA based on these indicators. Methods: This was a retrospective case-control study. We evaluated the renal function indicators of 127 severe preeclampsia pregnant patients and 127 normal pregnant patients antenatally who delivered in Shijiazhuang Fourth Hospital from January 2022 to December 2022. Mann-Whitney U test and Chi-square test were used to compare the differences in clinical data between two groups. Spearman correlation analysis was used to determine the correlation between renal function indicators and newborn weight in severe preeclampsia pregnant patients. Receiver operating characteristic (ROC) curve was used to determine the optimal critical values of the above indicators, and multivariate logistic regression analysis was used to determine the independent risk factors for severe preeclampsia combined with SGA. Results: Blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA) in severe preeclampsia patients with SGA were higher than severe preeclampsia without SGA (p &lt; 0.05 vs. all groups). In the severe preeclampsia group, these indicators were significantly negatively correlated with birth weight (p &lt; 0.001 vs. all groups), whereas no correlation was observed in the control group. In the severe preeclampsia group, a ROC analysis was performed based on whether the infants were small for gestational age, and the indicators were divided into two groups according to the optimal cut-off value. After adjusting for confounding factors, elevated BUN (≥4.9 mmol/L) served as an independent risk factor for severe preeclampsia patients with SGA (odds ratio (OR) = 4.336, 95% confidence interval (95% CI): 1.781–10.552, p = 0.001), and the corresponding area under the curve was 0.661 (0.572, 0.743). Conclusions: Serum renal function indicators in pregnant patients with severe preeclampsia were significantly associated with the occurrence of small for gestational age (SGA) infants. Moreover, elevated maternal BUN levels (≥4.9 mmol/L) prior to delivery may indicate the occurrence of SGA. However, we also acknowledge that the predictive power of this single marker is limited.

Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy.

To explore PTEN-induced putative kinase 1 (PINK1) expression and its clinical value in diabetic nephropathy. Ninety patients with diabetic nephropathy were recruited and divided into metformin hydrochloride monotherapy group, telmisartan monotherapy group and combination therapy (metformin and telmisartan) group. Renal function indices and PINK1 expression, inflammatory factors, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels were detected. The correlation between PINK1 and inflammatory factors, renal function indicators including estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and serum creatinine (SCr)] were analyzed by Pearson correlation. Following treatments, the combination therapy group exhibited increased PINK1 expression levels and decreased ROS levels compared to the groups receiving metformin hydrochloride or telmisartan monotherapy. The combination therapy group showed significant improvements in renal function indices and inflammatory markers. Additionally, the MMP ratio in the combination therapy group was higher compared to the two monotherapy groups. Furthermore, PINK1 was negatively correlated with UACR, SCr, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), while positively correlated with eGFR and interleukin-2 (IL-2). PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study.

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0-4), PCS Group 2 (PCS 5-19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.