Elevated Serum Creatinine Research Articles

Behavioral, Maternal and Neurological Effects of Monosodium Glutamate on Pregnant Female Rats During Early and Late Gestation

Seventy-five adult Wistar Albino rats were used in this experiment to detect the effect of MSG on fetus morphology, and pregnant rats’ behavioral, biochemecal, and neurological parameters. They were housed under standard laboratory conditions in plastic cages in a quiet environment with free access to food and water. They were randomly assigned into 4 groups of three replicates for each. Group (1) control, received normal saline. Groups (2, 3, and 4) received daily MSG orally at a dose of 1, 3 and 6 mg/kg respectively for a period of 20 days. There was a reduction in the mean number of fetuses /dam, an altered distribution of implantation, reduction in fetuses’ weight & length, besides some fetuses revealed morphological anomalies and skeletal defects at the 19th day of gestation. In addition, there was a decrease in the number of entrance and spontaneous alternations, increase in line crossing and rearing behaviors, elevation in serum ALT, AlP and creatinine, decrease in serum progesterone, increase in dopamine and glutamate levels (ng/mL) in brain tissues of MSG treated pregnant rats. So that, this study suggests that to diminish MSG in foods during pregnancy to to stay away from harmful effects on pregnant females behavior, brain tissue, and safe fetuses from deformity.

Therapeutic potential of black seed oil in treating rheumatoid arthritis: Insights on biochemical and genetic analyses of inflammatory signaling transducer

Nigella sativa (Black seed) has been a longstanding component of traditional medicine. Rheumatoid arthritis, an autoimmune disorder targeting bone, cartilage, and synovial cells, leads to enduring joint damage due to pathological immune responses. This study aims to assess the effectiveness of black seed oil in treating rheumatoid arthritis using a rat model. Fifty male albino rats were randomly assigned to five groups: control, induced arthritis, induced arthritis treated with black seed oil, induced arthritis treated with hydroxychloroquine, and induced arthritis treated with a combination of black seed oil and hydroxychloroquine. Arthritis was induced in the rats using single dose of 0.1 ml of Complete Freunds Adjuvant. Biochemical and genetic analyses of signaling transducers (IFNγ, IL-4, STAT3, and IL-12) were conducted on blood samples and stifle joints. Results indicated that induced arthritis led to elevated serum AST, ALT activities, creatinine, urea, FBS, RF, Anti-CCP, and CRP, along with reduced serum TAC. Additionally, there was an upregulation of IL-12, IFNγ, and STAT3 genes, and a downregulation of IL-4 gene compared to the normal control group. Treatment with black seed oil or hydroxychloroquine individually demonstrated notable improvements in these parameters, although the combined treatment showed less marked improvement. In conclusion, black seed oil demonstrates potential therapeutic benefits in alleviating the negative impacts of rheumatoid arthritis.

Imperatorin ameliorates kidney injury in diabetic mice by regulating the TGF-β/Smad2/3 signaling axis, epithelial-to-mesenchymal transition, and renal inflammation

Diabetic nephropathy (DN) is a serious concern in patients with diabetes mellitus. Prolonged hyperglycemia induces oxidative damage, chronic inflammation, and build-up of extracellular matrix (ECM) components in the renal cells, leading to kidney structural and functional changes. Imperatorin (IMP) is a naturally occurring furanocoumarin derivative with proven antioxidative and anti-inflammatory properties. We investigated whether IMP could improve DN and employed high glucose (HG)-induced HK-2 cells and high-fat diet-fed streptozotocin (HFD/STZ)-generated DN experimental model in C57BL/6 J mice. In vitro, IMP effectively reduced the HG-activated reactive oxygen species generation, disturbance in the mitochondrial membrane potential (MMP) and epithelial-to-mesenchymal transition (EMT)-related markers, and the transforming growth factor (TGF)-β and collagen 1 expression in HK-2 cells. In vivo, we found an elevation of serum creatinine, kidney histology alterations, and collagen build-up in the kidneys of the DN control group. Also, we found that altered expression of EMT-related markers, upregulation of the TGF-β/Smad2/3 axis, and elevated pro-inflammatory molecules, TNF-α, IL-1β, IL-18 and phospho–NF–kB (p65) in the DN control group. IMP treatment did not significantly reduce the blood glucose level compared to the DN control group. However, IMP treatment effectively improved renal damage by ameliorating kidney histological changes and serum renal injury markers. IMP treatment restored renal antioxidants and exhibited anti-inflammatory effects in the kidneys. Moreover, the abnormal manifestation of EMT-related attributes and elevated levels of TGF-β, phospho-Smad2/3, and collagen 1 were also normalized in the IMP treatment group. Our findings highlight that IMP may be a potential candidate for treating DN.

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats.

Disability and mortality rates for renal failure are still increasing. DNA damage and oxidative stress intoxication from body metabolism, high blood glucose, or the environment cause significant kidney damage. Recently, we reported that Box A of HMGB1 (Box A) acts as molecular scissors, producing DNA gaps that prevent DNA damage in kidney cell lines and ultimately reverse aging phenotypes in aging rat models. The present study aimed to demonstrate the potency of Box A in preventing D-galactose (D-gal)-induced kidney injury. A Box A expression plasmid was constructed and administered to a rat model. D-gal was injected subcutaneously for eight weeks. Serum was collected to study renal function, and white blood cells were collected for DNA gap measurement. Kidney tissue was also collected for γ-H2AX and NF-κB immunostaining; Senescence-associated (SA)-beta-gal staining; and analysis of the mRNA expression of p16INK4A, TNF-α, and IL-6. Moreover, histopathology analysis was performed using hematoxylin & eosin and Masson trichome staining. Pretreatment with Box A administration prevented the reduction of DNA gaps and the consequences of the DNA damage response, which include elevated serum creatinine; high serum BUN; an increased positive SA-beta-gal staining area; overexpression of p16INK4A, NF-κB and senescence-associated secretory phenotype molecules, including IL-6, TNF-α; and histological alterations, including tubular dilation and collagen accumulation. Box A effectively prevents DNA gap reduction and all D-gal-induced kidney pathological changes at the molecular, histological, and physiological levels. Therefore, Box A administration is a promising novel therapeutic strategy to prevent DNA-damaging agent-induced kidney failure.

Fractional excretion of total protein in patients with nephrotic syndrome.

The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

The use of intravascular contrast media in patients with impaired kidney function - joint clinical practice position statement of the Polish Society of Nephrology and the Polish Medical Society of Radiology.

Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.

Pathological Characteristics of Ferroptosis in Kidney Tissues in Type 2 Diabetic Patients with Diabetic Kidney Disease.

Diabetes kidney disease (DKD) is a common complication of diabetes and is currently considered the primary cause of end-stage renal disease. Ferroptosis has been found to participate in the development of DKD. However, no ferroptosis-related markers have been evaluated in human DKD samples. This study aimed to examine the ferroptosis-related pathological alterations in DKD samples. This study enrolled patients with DKD at the Third Hospital of Hebei Medical University between January 2018 and December 2022, of whom 30 were diagnosed with DKD and 10 with non-DKD (CON). Clinical data of patients were collected, and hematoxylin-eosinstaining (H&E), PASM, and immunohistochemical staining were performed to evaluate pathological changes and the expression of ferroptosis-related proteins, including GPX4, ACSL4, Nrf2, TfR1, FTH, and FTL. Compared with the CON group, patients with DKD exhibited significantly elevated serum creatinine levels and reduced eGFR (P < 0.05). Iron content and the expression of the ferroptosis-related protein ACSL4 were significantly increased, while the expression of Nrf2 was significantly decreased in the renal tissues of patients with DKD (P all < 0.05). There were no differences in the expression of GPX4, TfR1, FTH, or FTL between the two groups. Nrf2 and ACSL4 expression were influential factors in the occurrence of DKD and both exhibited diagnostic value for DKD. Nrf2 was a protective factor (OR, < 1), whereas ACSL4 was a risk factor (OR, > 1). Ferroptosis-promoting gene profile was identified in DKD renal samples, indicating that ferroptosis may participate in the pathogenesis of DKD. The expression levels of Nrf2 and ASCL4 in the kidneys are related to the severity and progression of DKD.

Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.

TGF-β/Smad3 signaling plays a critical role in type 2 diabetes (T2D) and type 2 diabetic nephropathy (T2DN), but treatment by specifically targeting Smad3 remains unexplored. To develop a new Smad3-targeted therapy for T2D and T2DN, we treated db/db mice at the pre-diabetic or established diabetic stage with a pharmacological Smad3 inhibitor SIS3. The therapeutic effect and mechanisms of anti-Smad3 treatment on T2D and T2DN were investigated. We found that anti-Smad3 treatment on pre-diabetic db/db mice largely attenuated both T2D and T2DN by markedly reducing blood glucose levels, and inhibiting the elevated serum creatinine, microalbuminuria, and renal fibrosis and inflammation. Unexpectedly, although SIS3 treatment on the established diabetic db/db mice inhibited T2DN but did not significantly improve T2D. Mechanistically, we uncovered that inhibition of T2DN in SIS3-treated db/db mice was associated with effectively restoring the balance of TGF-β/Smad signaling by inhibiting Smad3 while increasing Smad7, thereby suppressing Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation via lncRNA Erbb4-IR and LRN9884-dependent mechanisms. We also revealed that inhibition of islet β cell injury by preventing the loss of islet Pax 6 could be the mechanism through which the pre-diabetic treatment, rather than the late SIS3 treatment on db/db mice significantly improved the T2D phenotype.

Prophylactic Effects of Coriander Aqueous Extract on

A broad spectrum carbamate fungicide called carbendazim (Carb) that is very crucial for preventing plant diseases. and is one of the most pervasive environmental pollutants with serious implications for both human and animal health. In the current study, the role of Coriandrum sativum seeds extract (CSE) on carbendazim induced rats renal toxicity. Carb induced significant elevation in serum creatinine, urea, potassium, kidney malondialdehyde (MDA), nitric oxide (NO), renal injury, PCNA and significant depletion in serum sodium, calcium, renal glutathione (GSH). Treatments of Carb with CSE (CSE+Carb and/or Carb+CSE) improved these parameters and reduced renal toxicity with best results for Carb+CSE than CSE+Carb. Serum phosphorus revealed no significant changes between different groups. The above findings support the hypothesis that the antioxidant characteristics of one or more of CSE constituents can reduce the testicular toxicity of Carb.

THE CHALLENGE OF KIDNEY DAMAGE DURING INTERVENTIONAL CARDIOLOGY PROCEDURES

Introduction: Contrast nephropat(CN) is a frequent cause of acute renal failure (ARF). The diagnosis is based on an elevation of serum creatinine of 0.5 mg/dl (= 44.2 µmol/l) and/or ? 25% of baseline creatinine. In 90% of patients developing AKI on PC, it classically occurs between 24 and 72 hours after the examination. Diuresis is generally preserved, proteinuria is minimal, and urine sediment shows only granular cylinders and few cells. The differential diagnosis is that of ARF caused by cholesterol emboli from invasive procedures in the suprarenal aorta. In the short term, AKI following coronary angiography is associated with procedural complications, a longer hospital stay (8.1 days versus 4.7 days p &lt; 0.001), and higher one-year mortality (12.1% versus 3.7%). Patients at risk of developing PC-related nephropathy, particularly those with chronic renal failure or concomitant hypovolemia, have the need for extrarenal purification in some cases, in addition to the risk of cardiovascular mortality. This makes contrast media nephropathy a serious event for which clinicians must be prepared. Objective:the aim of this work was to determine the incidence of NIPC in patients undergoing primary angioplasty and/or coronary angiography procedures and generate hypotheses about risk factors. Materials and methods In collaboration with the cardiology department, we conducted a longitudinal descriptive study between January 2019 and January 2021. It included a cohort of 180 patients undergoing emergency or cold angiocoronary angiography for diagnostic or therapeutic purposes. Clinical and biological follow-up was 3 months for all patients. Patients with a blood test including creatininelevels before the examination and creatinine levels at 3 days, 15 days, 1 month, and 3 months after the procedure were included. Those who had undergone PCI for anexamination other than coronary Results Characteristics of the overall population All patients hadnormal creatinine levels and were predominantly male (70.0%) with an average age of 60.8 years. Of these patients, 20.6% had diabetes, 18.2% hypertension and 6.4% heart failure (HF). The rate of IR was 20.8%. Descriptive study Comparison of patient characteristics with and without NCI: The multivariate logistic regression study demonstrated that diabetes mellitus (Odds Ratio (OR)=2.26 95% confidence interval (CI95%): 1.29-3.98, p=0.005), a left ventricular ejection fraction (LVEF) &lt; 45% (OR=2. 03 IC95% :1.22-3.39, p=0.007) and a quantity of iodinated contrast medium (ICP) &gt; 90ml (1.72 IC95%:.of iodinated contrast medium (ICP) &gt; 90ml (1.72 IC95%: 0.99-2.99, p=0.05) were predictive of the occurrence of NCI. It should be noted that age was linked to creatinine clearance, and it was through a reduction in renal function that advanced age was responsible for a higher incidence of CIN. Furthermore, the search for correlations between these five independent factors 2 by 2 showed a significant relationship between diabetes and reduced renal function in the co-presence of these two factors, their effects are reciprocally potentiated and are responsible for an increased risk. Preventive measures showed? their efficacý only in the diabetic group, where prior hydration with saline significantly reduced the incidence of CIN: 16% versus 50% in diabetics who did not receive saline infusion Conclusion: Despite current management, this pathology affects the cardiovascular prognosis of patients, even though normalization of renal function is usually achieved within a month of exploration. In addition to identifying factors predictive of NIPC with a view to implementing appropriate preventive measures in patients at risk, we stress the importance of ensuring a good hemodynamic state intra-procedurally27.

Development, optimization, and assessment of losartan nano-bilosomes to mitigate diabetes-induced microvascular complications in Sprague Dawley rats

Losartan has a significant renal protection effect in type 2 diabetic patients. It was loaded into bilosomes to overcome its low oral bioavailability and improve its renal protective effects. The bilosomes were optimized using a 23 factorial design. Bile salt type and concentration and phospholipid concentration influenced the vesicles percent drug entrapment efficiency (%EE), vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP). The %EE varied from 71.73 ± 0.91 % to 92.34 ± 0.75 %. VS varied from 146.87 ± 3.56 to 286.29 ± 1.72 nm while PDI ranged from 0.28 ± 0.02 to 0.46 ± 0.03. ZP was high enough (−28.34 ± 0.61 to −35.64 ± 1.38 mV) to afford colloidal stability to the bilosomes. The bilosomes had the ability to prolong the release of the drug, with the percentage of losartan released after 12 h ranging from 64.31 ± 1.03 % to 88.48 ± 0.93 %. An optimized formulation was selected and used orally in an in vivo diabetic nephropathy rats model to study its ability to improve losartan nephroprotective effects. The diabetic group exhibited elevated serum creatinine, blood urea nitrogen (BUN), urine albumin, and inflammatory cytokines. Losartan bilosomes demonstrated reduced BUN and proteinuria compared to the free drug. Additionally, they outperformed the free drug in enhancing kidney function, preserving renal cellular structure, and mitigating diabetic renal inflammation and fibrosis. This was evidenced by significantly lower levels of tumor necrosis factor-alpha, interleukin-6, nuclear factor kappa, and macrophage markers. These findings conclusively demonstrate the promising potential of losartan bilosomes as an effective oral formulation to mitigate diabetic nephropathy.

A Machine Learning Algorithm Predicting Acute Kidney Injury in Intensive Care Unit Patients (NAVOY Acute Kidney Injury): Proof-of-Concept Study.

Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short- and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with previously published prediction algorithms designed to predict AKI onset in accordance with Kidney Disease: Improving Global Outcomes diagnosis criteria, with an impressive area under the receiver operating characteristics curve (AUROC) of 0.91 and an area under the precision-recall curve (AUPRC) of 0.75. The algorithm's predictive performance was externally validated on an independent hold-out test data set, confirming its ability to predict AKI with exceptional accuracy. NAVOY Acute Kidney Injury is an important development in the field of critical care medicine. It offers the ability to predict the onset of AKI with high accuracy using only 4 hours of data routinely collected in ICU electronic health records. This early detection capability has the potential to strengthen patient monitoring and management, ultimately leading to improved patient outcomes. Furthermore, NAVOY Acute Kidney Injury has been granted Conformite Europeenne (CE)-marking, marking a significant milestone as the first CE-marked AKI prediction algorithm for commercial use in European ICUs.

Association between fasting stress hyperglycemia ratio and contrast-induced acute kidney injury in coronary angiography patients: a cross-sectional study.

Stress hyperglycemia ratio (SHR), an emerging indicator of critical illness, exhibits a significant association with adverse cardiovascular outcomes. The primary aim of this research endeavor is to evaluate the association between fasting SHR and contrast-induced acute kidney injury (CI-AKI). This cross-sectional study comprised 3,137 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI). The calculation of fasting SHR involved dividing the admission fasting blood glucose by the estimated mean glucose obtained from glycosylated hemoglobin. CI-AKI was assessed based on elevated serum creatinine (Scr) levels. To investigate the relationship between fasting SHR and the proportion of SCr elevation, piecewise linear regression analysis was conducted. Modified Poisson's regression analysis was implemented to evaluate the correlation between fasting SHR and CI-AKI. Subgroup analysis and sensitivity analysis were conducted to explore result stability. Among the total population, 482 (15.4%) patients experienced CI-AKI. Piecewise linear regression analysis revealed significant associations between the proportion of SCr elevation and fasting SHR on both sides (≤ 0.8 and > 0.8) [β = -12.651, 95% CI (-23.281 to -2.022), P = 0.020; β = 8.274, 95% CI (4.176 to 12.372), P < 0.001]. The Modified Poisson's regression analysis demonstrated a statistically significant correlation between both the lowest and highest levels of fasting SHR and an increased incidence of CI-AKI [(SHR < 0.7 vs. 0.7 ≤ SHR < 0.9) β = 1.828, 95% CI (1.345 to 2.486), P < 0.001; (SHR ≥ 1.3 vs. 0.7 ≤ SHR < 0.9) β = 2.896, 95% CI (2.087 to 4.019), P < 0.001], which was further validated through subgroup and sensitivity analyses. In populations undergoing CAG or PCI, both lowest and highest levels of fasting SHR were significantly associated with an increased occurrence of CI-AKI.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

Early and minimal changes in serum creatinine can predict prognosis in elderly patients receiving invasive mechanical ventilation: A retrospective observational study

BackgroundEmerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of <26.5 µmol/L within 48 h after invasive mechanical ventilation (MV) on the short-term mortality of critically ill patients in the geriatric population. MethodsWe conducted a retrospective, observational, multicenter cohort study enrolling consecutive elderly patients (≥75 years) who received invasive MV from January 2008 to December 2020. Recursive partitioning was used to calculate the ratio of SCr rise from baseline within 48 h after MV and divided into six groups, (1) <10%, (2) 10%–<20%, (3) 20%–<30%, (4) 30%–<40%, (5) 40%–<50%, and (6) ≥50%, where the reference interval was defined as the ratio <10% based on an analysis, which confirmed that the lowest mortality risk was found in this range. Clinical data and laboratory data were noted. Their general conditions and clinical characteristics were compared between the six groups. Prognostic survival factors were identified using Cox regression analysis. Kaplan–Meier survival analysis was employed for the accumulative survival rate. ResultsA total of 1292 patients (1171 men) with a median age of 89 (interquartile range: 85–92) with MV were suitable for further analysis. In all, 376 patients had any stage of early AKI, and 916 patients had no AKI. Among 916 non-AKI patients, 349 patients were in the ratio <10%, 291 in the 10%–<20% group, 169 in the 20%–<30% group, 68 in the 30%–<40% group, 25 in the 40%–<50% group, and 14 in the ≥50% group. The 28-day mortality rates in the six groups from the lowest (<10%) to the highest (≥50%) were 8.0%, 16.8%, 28.4%, 54.4%, 80.0%, and 85.7%, respectively. In the multivariable-adjusted analysis, patients with a ratio of 10%–<20% (hazard ratio [HR]=2.244; 95% confidence interval [CI]: 1.410 to 3.572; P=0.001), 20%–<30% (HR=3.822; 95% CI: 2.433 to 6.194; P <0.001), 30%–<40% (HR=10.472; 95% CI: 6.379 to 17.190; P <0.001), 40%–<50% (HR=13.887; 95% CI: 7.624 to 25.292; P <0.001), and ≥50% (HR=13.618; 95% CI: 6.832 to 27.144; P <0.001) had relatively higher 28-day mortality rates. The 90-day mortality rates in the six strata were 30.1%, 35.1%, 45.0%, 60.3%, 80.0%, and 85.7%, respectively. Significant interactions were also observed between the ratio and 90-day mortality: patients with a ratio of 10%–<20% (HR=1.322; 95% CI: 1.006 to 1.738; P=0.045), 20%–<30% (HR=1.823; 95% CI: 1.356 to 2.452; P <0.001), 30%–<40% (HR=3.751; 95% CI: 2.601 to 5.410; P <0.001), 40%–<50% (HR=5.735; 95% CI: 3.447 to 9.541; P <0.001), and ≥50% (HR=6.305; 95% CI: 3.430 to 11.588; P <0.001) had relatively higher 90-day mortality rates. ConclusionsOur study suggests that a ≥ 10% SCr rise from baseline within 48 h after MV was independently associated with short-term all-cause mortality in mechanically ventilated elderly patients.

Preventive effect and mechanism of compound Danshen dripping pills on contrast-induced nephropathy after percutaneous coronary interventional.

Contrast-induced nephropathy (CIN) is one of the most common complications after coronary stent implantation due to the extensive development of coronary catheterization technology. Compound Danshen dripping pills (CDDP) are clinically used as cardiovascular drugs, relieving systemic inflammatory response. Previous studies have observed that CDDP can decrease CIN incidence after coronary stent implantation with uncertain effectiveness. We conducted a prospective, randomized, single-center, single-blind, controlled trial. We enrolled patients 18 years and older with unstable angina pectoris and NSTEMI who underwent PCI at the Tianjin Chest Hospital between November 1, 2021, and November 31, 2022, and followed for 30 days. Patients were randomized to CDDP and hydration therapy (10 capsules three times/day; N = 411) or hydration only (N = 411). The primary outcome was the contrast nephropathy incidence, defined as an elevation in serum creatinine by more than 25% or 44 μmol/L from baseline within 48-72 h of contrast exposure. Secondary outcomes included major adverse cardiovascular events post-surgery and during follow-up. After 48 h of operation, the two groups had statistical significance in Scr and BUN values (80.0 ± 12.59 vs. 84.43 ± 13.49, P < 0.05; 6.22 ± 1.01 vs. 6.40 ± 0.93, P < 0.05). The difference in Scr in 72 h between the two groups was statistically significant (76.42 ± 10.92 vs. 79.06 ± 11.58, P < 0.05). The CIN incidence was significantly lower in the CDDP group than in the hydration group. The CIN risk was significantly elevated in patients with LVEF <50%, contrast volume ≥160 ml, and hypertension, after 48 and 72 h of operation. The serum inflammation index levels NGAL, TNF-α, oxidative stress indexes SOD, and MDA significantly differed between the two groups. However, there was no significant difference in serum apoptosis indexes Bax, Bcl-2, and Casepase-9. CDDP pre-treatment could prevent contrast-induced nephropathy. Inflammatory response and oxidative stress could be significant in the CDDP mechanism.

Clinical and Laboratory Characteristics and Associated Factors to Mortality in Neonates with Birth Asphyxia: A Prospective Observational Study

Aims: To describe the clinical and laboratory characteristics and to investigate associated factors with mortality of birth asphyxia. Methods: This was a prospective observational study conducted on a total of 120 asphyxiated neonates admitted to the Neonatal Intensive Care Unit (NICU). Results: Severe asphyxia was observed in 33.3%, and moderate asphyxia in 66.7% of the cases. The mortality rate was 19.2%. The common clinical features: apnea/gasping (45.8%), hypothermia (37.5%), lethargy (33.0%). The serious clinical signs: abnormal heart rate (15.8%), gastrointestinal bleeding (13.3%), oliguria and anuria (17.5%). The laboratory findings showed hypoglycemia (30.8%), elevated SGOT (45.0%), serum creatinine &gt; 133 µmol/l (31.7%), hyponatremia (35.0%), hypocalcemia (65.8%), elevated lactate &gt; 5mmol/l (53.6%). The factors that increased the risk of mortality in neonatal asphyxia were Apgar score at 5 min ≤ 5, seizure/coma, need for mechanical ventilation, serum creatinine &gt; 133 µmol/l, liver injury, and lactate ≥ 5 mmol/l. Conclusion: The mortality rate is still high, and elevated serum creatinine, elevated liver enzymes, elevated lactate, and low 5-minute Apgar scores increase the risk of death in asphyxiated neonates. Key words: birth asphyxia, mortality, risk factors, neonates.

Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.

Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy. Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks. STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities. The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock

BackgroundAcute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI). Here, we prospectively assess sRAI performance in a separate cohort.MethodsA secondary analysis of a prospective, multicenter, observational study of children with septic shock admitted to the pediatric intensive care unit from 1/2019 to 12/2022. The primary outcome was severe AKI (≥ KDIGO Stage 2) on Day 3 (D3 severe AKI), and we compared predictive performance of the sRAI (calculated on Day 1) to the original RAI and serum creatinine elevation above baseline (D1 SCr > Baseline +). Original renal angina fulfillment (RAI +) was defined as RAI ≥ 8; sepsis renal angina fulfillment (sRAI +) was defined as RAI ≥ 20 or RAI 8 to < 20 with platelets < 150 × 103/µL.ResultsAmong 363 patients, 79 (22%) developed D3 severe AKI. One hundred forty (39%) were sRAI + , 195 (54%) RAI + , and 253 (70%) D1 SCr > Baseline + . Compared to sRAI-, sRAI + had higher risk of D3 severe AKI (RR 8.9, 95%CI 5–16, p < 0.001), kidney replacement therapy (KRT) (RR 18, 95%CI 6.6–49, p < 0.001), and mortality (RR 2.5, 95%CI 1.2–5.5, p = 0.013). sRAI predicted D3 severe AKI with an AUROC of 0.86 (95%CI 0.82–0.90), with greater specificity (74%) than D1 SCr > Baseline (36%) and RAI + (58%). On multivariable regression, sRAI + retained associations with D3 severe AKI (aOR 4.5, 95%CI 2.0–10.2, p < 0.001) and need for KRT (aOR 5.6, 95%CI 1.5–21.5, p = 0.01).ConclusionsPrediction of severe AKI in pediatric septic shock is important to improve outcomes, allocate resources, and inform enrollment in clinical trials examining potential disease-modifying therapies. The sRAI affords more accurate and specific prediction than context-free SCr elevation or the original RAI in this population.

Brentuximab Vedotin in Combination with Methotrexate, L-Asparaginase, and Dexamethasone (B-MAD) As Frontline Treatment for Patients with Extranodal NK/T-Cell Lymphoma

Introduction Extranodal natural killer/T-cell lymphoma (ENKTL) is a unique lymphoma associated with Epstein-Barr virus infection. It is more common in Asia than in the Western. The prognosis is usually poor, especially in advanced disease, and no standard treatment exists. Brentuximab vedotin (BV) is a drug-conjugated monoclonal antibody which targets the cell-membrane protein CD30 linked to the potent anti-tubulin agent. Due to frequent expression of CD30 in ENKTL, we investigated the safety and efficacy of BV in combination with methotrexate, L-asparaginase, and dexamethasone (B-MAD) as frontline treatment in Thai patients with ENKTL. Methods The Thai Lymphoma Study Group conducted a prospective, multicenter phase I/II study and enrolled patients aged 18-60 years with newly diagnosed ENKTL between December 2018 and December 2021 from 9 hospitals in Thailand. Patients with localized ENKTL (stage I/II) received concurrent weekly cisplatin and involved-field radiation (IFRT) 40-50 Gy, followed by 3 cycles of B-MAD. Patients with advanced ENKTL (stage III/IV) received only B-MAD for 6 cycles. BV in combination with standard dose MAD chemotherapy was given every 21 days. The primary objective was to determine the safety and optimal dose of BV in B-MAD regimen using a 3+3 dose escalation design. The secondary objective was to evaluate the overall response rate (ORR) at the end of B-MAD treatment, safety, progression-free survival and overall survival. An analysis was performed at the data cutoff date of June 30, 2023. Results Thirty-four patients (pts.) were enrolled; 23 had localized and 11 had advanced diseases. The median age was 42 years (range, 18-59). Four pts. in the localized group did not receive B-MAD due to disease progression during concurrent cisplatin and IFRT (n=3) and consent withdrawal (n=1). Six pts. received B-MAD in phase I study (3 pts. at 1.2 mg/kg and 3 pts. at 1.8 mg/kg of BV). No dose-limiting toxicity was observed among six patients, therefore the recommended dose of BV in phase II study was 1.8 mg/kg. Of 30 evaluable pts., 20 (66.7%) achieved complete response (CR), 5 (16.7%) had partial response, and 5 (16.7%) progressed after treatment. The response rates (ORR/CR rate) in localized and advanced diseases were 89.5%/78.9% and 72.7%/45.5%, respectively. A total of 190 adverse events (AEs) were reported. The most common AEs were anemia 19/190 (10%), leukopenia 9/190 (4.7%), neutropenia 9/190 (4.7%), hypoalbuminemia 9/190 (4.7%), peripheral neuropathy 7/190 (3.7%), elevated ALT 7/190 (3.7%), and elevated serum creatinine level 5/190 (2.6%), respectively. Twenty-four events were classified as grade ≥ 3 including anemia (4/24), leukopenia (7/24), neutropenia (7/24), and elevated ALT (1/24), respectively. A total of 21 serious adverse events (SAEs) were reported. The causes of SAE were varied as follows: acute kidney injury 2/21, pneumonia 2/21, leukopenia 1/21, neutropenia 1/21, and thrombocytopenia 1/21. Most of the SAEs were suspected to be related to the treatment. Two cases of acute kidney injury related to methotrexate and one case of hypersensitivity reactions to L-asparaginase were reported as SAEs. They were manageable and completely resolved upon follow-up. There were no treatment-related deaths. At the data cutoff date, after the median follow up of 11.6 months, 25 pts. were alive, 7 experienced progressions, and 5 had died. Two pts. had progression in the central nervous system. Conclusion Treatment with standard-dose of BV in combination with MAD chemotherapy was well tolerated and showed encouraging efficacy in patients with newly diagnosed ENKTL. Evaluation of long-term survival data is ongoing. (ClinicalTrials.gov identifier: NCT03246750)