Impaired Renal Function Research Articles

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

Development of a quick guide for assessment of the most frequently used renal risk medication in Danish hospitals and primary care.

Due to changes in pharmacokinetics and pharmacodynamics, patients with impaired renal function suffer an increased risk of suboptimal and potentially harmful medication treatment. This necessitates careful consideration of medications affected by impaired renal function when performing medication reviews. The aim of this study was to develop a quick guide (a list of recommendations) for assessing renal risk medications in medication reviews led by hospital pharmacists. The list was based on the 100 most frequently used medications in Danish hospitals and primary care. After combining the 200 records, 29 duplicates were excluded resulting in a pool of 171 medications. Assessment by two clinical pharmacists led to the exclusion of 121 medications. Of the remaining 50 medications, seven were discussed among the two pharmacists, and two of these were also in the research group to reach a consensus. The renal risk quick guide comprised 50 medications. The most prevalent medications on the list were from Anatomical Therapeutic Chemical Classification System (ATC)-group N, C and L. Recommendations from two databases were included in the quick guide in order to provide clinical pharmacists with existing, updated evidence on medication use in impaired renal function. The next step is to test the feasibility of the quick guide in daily practice when performing medication reviews.

Influence of contrast medium on long-term renal function and outcomes in patients with septic acute kidney injury: A propensity-matched cohort study

PurposeTo investigate the relationship between contrast medium administration and long-term mortality and renal function in patients with septic acute kidney injury (AKI). Materials and methodsWe performed a retrospective, propensity-matched cohort study involving 1521 adult patients admitted with septic shock. Patients with septic AKI who underwent contrast or non-contrast CT scans were enrolled. The primary outcomes were the rates of 90-day mortality and dialysis within 90 days. The secondary outcomes included worsening of AKI, in-hospital mortality, and maintenance of dialysis after 90 days. ResultsDuring the study period, 609 patients with septic AKI were identified; 220 (36.1%) underwent contrast CT and 389 (63.9%) underwent non-contrast CT. After propensity score matching, 133 pairs were obtained. There were no significant differences between the contrast and non-contrast CT groups in 90-day mortality (54.9% vs. 58.6%, P = 0.579), dialysis within 90 days (6.8% vs. 8.3%, P = 0.655), worsening AKI (2.3% vs. 3.0%, P = 0.706), in-hospital mortality (10.6% vs. 14.4%, P = 0.369), or maintenance of dialysis after 90 days (0.0% vs. 0.8%, P > 0.99). ConclusionsThe administration of intravenous contrast medium was not associated with long-term mortality, deterioration of renal function, or dialysis in patients with septic AKI.

Predictive and Diagnostic Value of the Angiogenic Proteins in Patients With Chronic Kidney Disease.

Our objective was to investigate the predictive and diagnostic accuracy of the angiogenic proteins sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) for preterm preeclampsia and explore the relationship between renal function and these proteins. We completed a blinded, prospective, longitudinal, observational study of patients with chronic kidney disease followed at a tertiary center (2018-2023). Serum samples were obtained at 3 time points along gestation (planned sampling): 12-16, 18-22, and 28-32 weeks. In addition, samples were obtained whenever preeclampsia was suspected (indicated sampling). sFlt-1 and PlGF levels remained concealed until the study ended. The primary outcome was preterm preeclampsia. The planned and indicated samples were used to estimate the predictive and diagnostic accuracy of the angiogenic proteins, respectively. Of the 97 participants, 21 (21.6%) experienced preterm preeclampsia. In asymptomatic patients with chronic kidney disease, the angiogenic proteins were predictive of preterm preeclampsia only when sampled in the third trimester, in which case the sFlt-1/PlGF ratio (false positive rate of 37% for a detection rate of 80%) was more predictive than either sFlt-1 or PlGF in isolation. In patients with suspected preeclampsia, the diagnostic accuracy of the sFlt-1/PlGF ratio (false positive rate of 26% for a detection rate of 80%) was higher than that of sFlt-1 and PlGF in isolation. Diminished renal function was associated with increased levels of PlGF. sFlt-1 and PlGF can effectively predict and improve the diagnostic accuracy for preterm preeclampsia among patients with chronic kidney disease. The optimal sFlt-1/PlGF ratio cutoff to rule out preeclampsia may need to be lower in patients with impaired renal function.

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts.

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as a specific kidney fibroblast marker. Gucy1α1 levels significantly increased over the course of two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that Gucy1α1 comprehensively labelled cortical and medullary quiescent and activated fibroblasts in the control kidney and throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) and vimentin (Vim), Gucy1α1 did not overlap with off-target populations such as podocytes. Notably, Gucy1α1 labelled kidney fibroblasts in both male and female mice. Furthermore, we observed elevated Gucy1α1 expression in the human fibrotic kidney and lung. Studies in the murine models of cardiac and liver fibrosis revealed Gucy1α1 elevation in activated Pdgfrβ-, Vim- and alpha smooth muscle actin (αSma)-expressing fibroblasts paralleling injury progression and resolution. Overall, we demonstrate Gucy1α1 as an exclusive fibroblast marker in both sexes. Due to its multiorgan translational potential, Gucy1α1 might provide a novel promising strategy to specifically target and mechanistically examine fibroblasts.

Population Pharmacokinetic of Vancomycin Administered by Continuous Infusion in Critically Ill Patients

Introduction: Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes. Objective: The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions. Methods: The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model’s Pk parameters. The performance of the final model was assessed using an external dataset. Results: A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance. Conclusion: We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic.

Association between pregnancy-related changes in serum creatinine and preeclampsia diagnosis

BackgroundPreeclampsia is a leading cause of maternal and neonatal morbidity and mortality, affecting 2–8% of all pregnancies. Typically, the increased glomerular filtration rate of pregnancy results in a decrease in serum creatinine. It is unknown if women without the expected decrease in serum creatinine during pregnancy are more likely to be diagnosed with preeclampsia.ObjectiveWe sought to determine if the absence of a pregnancy-related decrease in serum creatinine was associated with the development of preeclampsia in patients deemed to be at high risk for developing preeclampsia. We hypothesized that the absence of the expected decrease in serum creatinine may be a marker of impaired renal function and therefore may be associated with increased risk of preeclampsia in this cohort.Study designWe conducted a retrospective cohort study of deliveries between November 2, 2017 and June 30, 2020 at a single institution. Pregnancies were included if a baseline serum creatinine (measured between one year prior to conception through 6 weeks gestation), and another serum creatinine value prior to 20 weeks of gestation were measured. Decrease in serum creatinine was defined as any decrease (at least 0.01 mg/dL) from baseline. The primary outcome was diagnosis of preeclampsia. Exclusion criteria included fetal anomalies, fetal demise, multiple gestation, or delivery prior to 20 weeks. Bivariable analyses were performed using Chi-square, ANOVA, and Student’s t test. Logistic regression was used to determine odds of developing preeclampsia controlling for confounders.ResultsWe identified 392 pregnancies that met inclusion criteria. Preeclampsia was diagnosed in 56 (14.3%) pregnancies. Patients diagnosed with preeclampsia were more likely to have a history of preeclampsia in a prior pregnancy, chronic hypertension (HTN), and diabetes. They were also more likely to have aspirin prescribed in the current pregnancy. Prevalence of advanced maternal age, multiparity, obesity, smoking, history of autoimmune disease, history of CKD, gestational HTN, or multiple pregnancy were not significantly different between patients with and without a diagnosis of preeclampsia. After controlling for confounders, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia (OR 0.76, CI 0.32–1.78).ConclusionAfter controlling for risk factors associated with preeclampsia, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia in this high-risk cohort.

Population Pharmacokinetics of Loxoprofen and its alcoholic metabolites in healthy Korean men.

Loxoprofen has been actively used clinically to relieve musculoskeletal pain and inflammatory symptoms. However, there are few reports on quantitative pharmacokinetic (PK) prediction tools and diversity analyzes for loxoprofen within populations. The aim of this study was to identify effective covariates associated with explaining inter-individual PK variability through a population pharmacokinetic (Pop-PK) modeling approach for loxoprofen, and to provide a starting point for establishing scientific dosing regimens. The bioequivalence PK results of loxoprofen performed on 52 healthy Korean men and the physiological and biochemical parameters derived from each individual were used as base data for the development of a Pop-PK model of loxoprofen. In order to simultaneously predict the PKs of the active form according to loxoprofen exposure, previously reported PK results of trans-alcohol loxoprofen, an active metabolite of loxoprofen, were used to expand the model. The Pop-PK profiles of loxoprofen were described in terms of the basic structure of a non-sequential two absorption with 2-disposition compartment, and for inter-individual PK variations, peripheral compartment volume of distribution could be correlated with body surface area (BSA), and central compartment clearance with creatinine clearance (CrCL) and albumin levels. As a result of the model simulation, the concentrations of loxoprofen and its alcoholic metabolites in plasma significantly decreased as CrCL and albumin levels increased and decreased, respectively. On the other hand, it was confirmed that the higher the BSA, the greater the distribution of loxoprofen to the periphery, and the minimum concentrations of loxoprofen and alcoholic metabolites in plasma in steady-state increased by approximately 1.78-2 times, while the fluctuation between maximum and minimum concentrations decreased. The results suggest that patients with large BSA, impaired renal function, and high serum albumin levels may have significantly higher plasma exposure to loxoprofen and trans-alcohol loxoprofen. It was also suggested that the potential side effects in the gastrointestinal system and various tissues and the level of exposure in plasma due to long-term application of loxoprofen in this patient group could be causally explained. This study provides a very useful starting point for a scientific precision medicine approach to loxoprofen by discovering effective covariates and establishing a quantitative model that can explain the diversity of loxoprofen PKs within the population. The clinical study protocol used in this study was thoroughly reviewed and approved by the Institutional Review Board of the Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Republic of Korea. The bioequivalence study permit numbers are as follows: 041113; 10.15.2004.

Impaired renal function with elevated remnant cholesterol related to risk of atherosclerotic cardiovascular disease: The copenhagen general population study

Impaired renal function with elevated remnant cholesterol related to risk of atherosclerotic cardiovascular disease: The copenhagen general population study

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.

The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of mitiperstat.

Mitiperstat is a novel, highly potent myeloperoxidase inhibitor being evaluated in patients with cardio-metabolic disease (phase 2). These patients often have impaired renal function, which may affect mitiperstat pharmacokinetics. This study assessed mitiperstat pharmacokinetics, safety and tolerability in participants with severe renal impairment and normal renal function, to inform inclusion of participants with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 in phase 3. Participants with severe renal impairment (eGFR ≥15 and <30 mL/min/1.73 m2) who were not on dialysis (n = 10) and group-matched controls (eGFR ≥90 mL/min/1.73 m2; n = 10) received a single mitiperstat 2.5mg oral tablet. Blood samples were collected at intervals for 2weeks and urine samples for 24 h post-dose. Total apparent mitiperstat clearance was 10.83 L/h in the severe renal impairment cohort and 25.62 L/h in the control cohort. The area under the plasma concentration-time curve was 2.37-fold higher (90% confidence interval [CI]: 1.79, 3.12) in the severe renal impairment cohort than in the control cohort, with longer elimination half-life and similar maximum concentration. Non-renal clearance was similar between the cohorts. Mitiperstat apparent clearance was approximately twofold lower in individuals with severe renal impairment than in those with normal renal function. Lower clearance was driven by reduced renal clearance; non-renal clearance was similar. Mitiperstat was generally well tolerated by participants with severe renal impairment and normal renal function. These findings, together with efficacy and safety/tolerability data from phase 2b, will guide the dosing regimen for phase 3.

Coagulation Risk Predicting in Anticoagulant-Free Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is a prolonged continuous extracorporeal blood purification therapy to replace impaired renal function. Typically, CRRT therapy requires routine anticoagulation, but for patients at risk of bleeding and with contraindications to sodium citrate, anticoagulant-free dialysis therapy is necessary. However, this approach increases the risk of CRRT circuit coagulation, leading to treatment interruption and increased resource consumption. In this study, we utilized artificial intelligence machine learning methods to predict the risk of CRRT circuit coagulation based on pre-CRRT treatment metrics. We retrospectively analyzed 212 patients who underwent anticoagulant-free CRRT from October 2022 to October 2023. Patients were categorized into high-risk and low-risk groups based on CRRT circuit coagulation within 24 h. We employed eight machine learning methods to predict the risk of circuit coagulation. The performance of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic. 5-fold cross-validation was used to validate the machine learning models. Feature importance and SHAP plots were used to interpret the model's performance and key drivers. We identified 88 patients (41.51%) at high risk of circuit coagulation within 24 h of CRRT. Our machine learning models showed excellent predictive performance, with ensemble learning achieving an AUC of 0.863 (95% CI: 0.860-0.868), outperforming individual algorithms. Random forest was the best single-algorithm model, with an AUC of 0.819 (95% CI: 0.814-0.823). The top three features identified as most important by the SHAP summary plot and feature importance graph are platelet, filtration fraction (FF), and triglycerides. We created a model using machine learning to predict the risk of circuit coagulation during anticoagulant-free CRRT therapy. Our model performs well (AUC 0.863) and identifies key factors like platelets, FF, and triglycerides. This facilitates the development of personalized treatment strategies by clinicians aimed at reducing circuit coagulation risk, thereby enhancing patient outcomes and reducing healthcare expenses.

Intrarenal venous flow patterns - Guiding fluid management in sepsis with AKI: A case report.

Sepsis often leads to acute kidney injury (AKI), presenting significant challenges in fluid management. This study explores the potential of analyzing intrarenal venous flow (IRVF) patterns to guide tailored fluid therapy, aiming to improve patient outcomes. A patient was admitted to the intensive care unit with symptoms of septic shock, including fever, severe hypotension, and altered mental status, secondary to a perforated ascending colon adenocarcinoma. The patient was diagnosed with perforated ascending colon adenocarcinoma, septic shock, and AKI. Clinical findings included elevated inflammatory markers and impaired renal function. The primary therapeutic interventions included surgical resection of the perforated colon, administration of broad-spectrum antibiotics, and fluid resuscitation. Fluid management was guided by continuous monitoring of IRVF, which facilitated precise adjustments to optimize fluid balance and renal perfusion. By utilizing IRVF patterns to guide fluid therapy, the patient's circulatory status and renal function significantly improved. The individualized fluid management approach contributed to better stabilization of the patient's condition. This case underscores the potential utility of IRVF patterns in guiding fluid management strategies for patients with sepsis and AKI. The main is the benefit of IRVF-guided fluid therapy in improving patient outcomes. Further research is warranted to validate the efficacy and safety of this approach, with the aim of enhancing clinical outcomes in critically ill patients.

HEART FAILURE AND CHRONIC KIDNEY DISEASE: PROGNOSIS AND THERAPEUTIC AND SURGICAL OPTIONS.

Heart failure (HF) and chronic kidney disease (CKD) are frequently interrelated conditions that significantly affect patients' quality of life and survival. Both conditions share common risk factors, such as diabetes mellitus and hypertension, and can exacerbate each other. HF can lead to deterioration in renal function due to reduced renal blood flow and activation of neurohormonal mechanisms. Conversely, CKD can worsen HF by causing volume overload and disrupting electrolyte balance. Managing these conditions requires an integrated approach that considers the complex interactions between the cardiovascular and renal systems. Objective: To analyze the therapeutic and surgical options available for treating heart failure in patients with chronic kidney disease and evaluate their impact on patients' prognosis. Methodology: The study followed the PRISMA checklist and involved a systematic search of PubMed, Scielo, and Web of Science databases. Keywords included "heart failure," "chronic kidney disease," "therapeutic options," "surgical options," and "prognosis." Inclusion criteria were articles published in the last 10 years, studies addressing both HF and CKD, and research providing data on therapeutic or surgical interventions. Studies focusing solely on one condition, articles outside the review's scope, and non-peer-reviewed research were excluded. Results: The results indicated that an integrated treatment approach, including risk factor management, specific pharmacotherapy, and surgical interventions, can significantly improve patient prognosis. Therapeutic options, such as ACE inhibitors and angiotensin receptor blockers, have shown benefits in reducing symptoms and disease progression. Surgical interventions, such as coronary revascularization and kidney transplantation, were also associated with improvements in clinical outcomes. Conclusion: Emphasized that a combined and multidisciplinary approach is essential to optimize treatment and quality of life for these patients, highlighting the importance of personalized and integrated strategies for therapeutic success.

Joint effects of sleep disturbance and renal function impairment on incident new-onset severe metabolic dysfunction-associated steatotic liver disease.

To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD). The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD. Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk. This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.

Role of Urinary Matrix Metalloproteinase-7 (MMP-7) as an Early Marker of Renal Dysfunction in Diabetic Individuals: A Cross-Sectional Study.

The matrix metalloproteinase 7(MMP-7) level gets heightened in the urine samples of diabetic individuals with impaired renal function. Renal biopsy is seldom offered because of its invasive nature. These concerns spurred the investigation of relationships between urine MMP-7 levels and the renal function of diabetic individuals. Studies exploring this aspect are scarce. We aimed to evaluate the glycemic and renal parameters of female and male individuals with or without type 2 diabetes mellitus (T2DM) or kidney disease. We also assessed the correlation of urine MMP-7 with various parameters. This prospective, analytical, cross-sectional study was conducted at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from February 2020 to January 2023. Female and male individuals 18-85 years of age diagnosed with either T2DM, hypertension, or kidney disease were assessed for their glycemic indices and renal parameters. Those with both renal disease and T2DMwere placed in group A. The diabetic individuals without kidney disease constituted group B. People in group C had neither kidney disease nor T2DM. Patients in group D had kidney disease but were not diabetics. The parameters of the male and female participants in each of the four groups were assessed and compared, including: age, body mass index (BMI), fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), serum urea, serum creatinine, estimated glomerular filtration rate (eGFR), urine albumin, urine creatinine, urine albumin-creatinine ratio (ACR), serum sodium, serum potassium, and urine MMP-7 levels. Furthermore, we correlated urine MMP-7 with all these traits. We used R software (version 4.4.0, Vienna, Austria) for data analysis. Two hundred eighty-seven (87.5%) of the 328 individuals we screened were eligible. Of them, group A had the maximum number (94) of participants, followed by B (75), C (65), and D (53). Males comprised 60.3% (n = 173) of the study population. The median age of the participants was 52.0 (44.0-61.1) years. The intergroup variations were statistically significant (p < 0.001) owing to their glycemic status and renal function. The gender-basis comparison of FBS and HbA1c yielded non-significant differences. On the contrary, assessment of the renal parameters revealed significant differences (p < 0.001) between females and males. The study population had a median urine MMP-7 level of 19.9 (1.1-50.5) µg/L. Significant associations with urine MMP-7 were found with serum creatinine (r = 0.91, p < 0.001), urine ACR (r = 0.86, p < 0.001), and eGFR (r = -0.84, p < 0.001). Our study portrayed that male diabetics, in comparison to female diabetics, had greater levels of urine ACR, urine MMP-7, eGFR, and serum creatinine. Moreover, urine ACR, eGFR, and serum creatinine strongly correlated with the urine MMP-7 level.

Levosimendan: A New Therapeutical Strategy in Patients with Renal Insufficiency.

Levosimendan, a Ca2 + sensitizer with positive inotropic effects, is primarily employed for the short-term treatment of acute decompensated heart failure (ADHF). Levosimendan exerts renal function protection through various mechanisms, including anti-apoptosis, anti-inflammatory, and antioxidant effects in vivo. Additionally, levosimendan may have a protective effect on individuals with heart failure and renal insufficiency, as well as on renal function impairment after cardiac surgery. However, the application of levosimendan in patients with severe renal dysfunction remains controversial. This article delves into the use of levosimendan in severe renal insufficiency, explores its impact on renal function, and provides a comprehensive overview of its impact on renal function after cardiac surgery.

Prevalence and determinants of failure to thrive in children with vesico-ureteral reflux.

To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico-ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses. We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided. Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch-up growth. The remaining six patients exhibited spontaneous catch-up growth. FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases.

Cascading renal injury after brain death: Unveiling glycocalyx alteration and the potential protective role of tacrolimus.

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain death-induced renal injury. This study aimed to investigate changes associated with brain death-induced renal injury in a 4-month-old female porcine model. The experimental groups included brain death placebo-pretreated (BD; n = 9), brain death tacrolimus-pretreated using the clinical dose of 0.25mg/kg the day before surgery, followed by 0.05mg/kg/day 1hour before the procedure (BD + FK506; n = 8), and control (ctrl, n = 7) piglets, which did not undergo brain death induction. Furthermore, we aimed to assess the effect of FK506 on these renal alterations through graft preconditioning. We hypothesized that immunosuppressive properties of FK506 reduce tissue inflammation and preserve the glycocalyx. Our findings revealed a series of interconnected events triggered by BD, leading to a deterioration of renal function and increased proteinuria, increased apoptosis in the vessels, glomeruli and tubules, significant leukocyte infiltration into renal tissue, and degradation of the glycocalyx in comparison with ctrl group. Importantly, treatment with FK506 demonstrated significant efficacy in attenuating these adverse effects. FK506 helped reduce apoptosis, maintain glycocalyx integrity, regulate neutrophil infiltration, and mitigate renal injury following BD. This study offers new insights into the pathophysiology of BD-induced renal injury, emphasizing the potential of FK506 pretreatment as a promising therapeutic intervention for organ preservation, through maintaining endothelial function with the additional benefit of limiting the risk of rejection.

Silibinin-loaded Nanostructured Lipid Carriers (NLCs) Ameliorated Lead-induced Acute Nephrotoxicity in Male Rats.

As a toxic heavy metal, lead (Pb) is well known for impairment of renal function due to oxidative injuries. In contrast, the antioxidant activity of silibinin has been approved. Given the role of silibinin antioxidant activity, the present study investigated the effectiveness of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against Pb-induced acute nephrotoxicity in rats. The emulsification-solvent evaporation method was applied to prepare Sili-NLCs. Sixty male Wistar rats were divided into ten separate groups. Pb (20 mg/kg/day, i.p.) was applied to induce nephrotoxicity and in the treatment groups animals received the same concentration of silibinin and Sili-NLCs (25, 50, and 100 mg/kg/day, p.o.) for five days. After sacrificing rats, kidney tissue samples were collected to assess the oxidative stress parameters, including lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. Also, histopathological examination using Hematoxylin-Eosin (H&E) was studied. Not only did Pb injection significantly increase the renal levels of LPO and NO, but also decreased the levels of antioxidant enzyme activity. On the other hand, Sili-NLCs were more effective than silibinin in decreasing renal oxidative damage by increasing the antioxidant defense system. Moreover, the histopathological examination correlated well with biochemical findings. Our data suggested that Sili-NLCs are potentially superior to pure silibinin for attenuating Pb-induced acute nephrotoxicity.