Markers Of Renal Function Research Articles

Sex-related changes in renal function markers, electrolytes and hematological indices of rats of different age groups in relation to protein excretion

Sex-related changes in renal function markers, electrolytes and hematological indices of rats of different age groups in relation to protein excretion

Changes in Bone Mineral Density and Related Influencing Factors Assessed by Quantitative Computed Tomography in Maintenance Dialysis Patients.

To investigate the changes in volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT) in chronic kidney disease (CKD) patients on maintenance dialysis. Descriptive study. Place and Duration of the Study: Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, from March to July 2022. Maintenance dialysis patients were selected for this study, and parameters related to renal function and bone metabolism markers were recorded. Patients undergoing routine physical examination were age-matched with maintenance dialysis patients to serve as the control group. vBMD scans of the lumbar spine (L1-3) were obtained by QCT for all participants. Among the 141 maintenance dialysis patients, there were 67 patients with secondary hyperparathyroidism (SHPT) and 74 patients with non-secondary hyperparathyroidism (non-SHPT) with mean vBMDs of 145.99±55.13 mg/cm3 and 129.10±44.20 mg/cm3, respectively. The 159 individuals in the control group had mean age of 52.77±11.66 years and mean vBMD of 129.62±36.36 mg/cm3. The vBMD of the SHPT group was greater than that of both the non-SHPT group and the control group (all p<0.05). For dialysis patients, vBMD was positively correlated with calcium-phosphorus product and intact parathyroid hormone (iPTH) levels (r = 0.181, 0.214, respectively, p<0.05); vBMD was inversely correlated with age (r = -0.555, p<0.05). After adjusting for the covariates, vBMD remained positively correlated with iPTH (r = 0.184, p<0.05). Increased lumbar vertebral vBMD in maintenance dialysis patients may be associated with high iPTH, providing clinicians with a new understanding of the changes in bone mineral density in maintenance dialysis patients. Bone mineral density, Quantitative computed tomography, Chronic kidney disease, Maintenance dialysis.

Serum Fibrinogen and Renal Dysfunction as Important Predictors of Left Atrial Thrombosis in Patients with Atrial Fibrillation.

As has been shown previously, patients with atrial fibrillation (AF) who have left atrial thrombus (LAT) also have elevated plasma concentrations of fibrinogen. In this study, we tried to determine if this is the consequence of a genetic trait and whether elevated concentrations of fibrinogen could be used to predict LAT in patients with AF. We recruited 181 consecutive patients scheduled for pulmonary vein isolation (PVI) or direct current cardioversion. The primary endpoint was the presence of LAT on transesophageal echocardiography (TOE). We recorded routine clinical and biochemical data as well as the polymorphism type of the fibrinogen gene for the β chain. To control potentially interfering variables, we performed propensity score matching (PSM). Multivariable and univariable logistic regression models (LRM) were computed using the CHA2DS2-Vasc score, the fibrinogen concentration and creatinine clearance as estimated by the Cockcroft-Gault equation. 60 of 181 patients had LAT as detected by TOE. As expected, patients with LAT had significantly higher concentrations of fibrinogen (3.9 vs. 3.6 g/L); p = 0.01 in the unadjusted analysis. After performing PSM, there were no statistically significant differences between the groups, except for creatinine clearance (79.9 vs. 96.8 mL/min); p = 0.01. There were also no differences regarding the -455 G/A βfibrinogen polymorphism distribution between the two groups. After constructing the LRM, we found no performance enhancement for the CHA2DS2-Vasc score by adding the fibrinogen concentration or creatinine clearance alone, but when all three variables were put together, there was a significant improvement in LAT prediction (AUC 0.64 vs. 0.72), p = 0.026. Our study found no evidence of elevated levels of circulating fibrinogen in patients with LAT or a connection between those levels and the A/A and A positive polymorphism. When used together with renal function markers such as creatinine clearance, plasma fibrinogen concentrations can provide additional power to the CHA2DS2-Vasc score for predicting LAT.

A-025 Principal Component Analysis as a Clustering Method for the Identification of Populations with Risk of Diabetes Development

Abstract Background Obesity is a chronic disease, defined by the World Health Organization as the abnormal or excessive accumulation of fat in the body. Overweight populations have grown epidemically in all age groups in recent decades and represent a major public health issue globally. Excess weight is one of the potential factors for insulin resistance, thus increasing the risk of developing type 2 diabetes. This study aimed to investigate the urea/creatinine ratio as a marker of renal function in individuals with different body mass index (BMI) levels and examine clusters with increased risk for diabetes development. Methods Study population and characteristics: This study was a 34-month retrospective analysis from a large laboratory database in the city of São Paulo, Brazil (January 2019–November 2022). Individuals ranging between 19–60 years old were selected based on the availability of BMI data and results for creatinine, urea, serum glucose, and glycated (A1C). Only outpatient results were included in the current analysis. The following parameters were included in this study: BMI (kg/m2): 18.5–24.9 (healthy), 25–29 (overweight), 30–34.9 (overweight level 1), 35–39.9 (overweight level 2), and ≥40 (overweight level 3). The definition of diabetes risk was as follows: (i) without diabetes risk: serum glucose&amp;gt;100 mg/dL and A1C &amp;lt; 5.7; (ii) transition to diabetes risk: serum glucose 101–125 mg/dL and A1C 5.7%–6.4%; (iii) diabetes risk: serum glucose &amp;gt;126 mg/dL and A1C &amp;gt; 6.4%. Statistical analysis: Principal component analysis (PCA) was performed resulting in a division of four subpopulation clusters based on the risk of diabetes development. One-way ANOVA with the Tukey test was used for intergroup comparison. For all results *P &amp;lt; 0.05 was considered statistically significant. Results A total of 667 participants met the inclusion criteria. From all BMI profiles, the overweight population in diabetes risk situation showed a significant difference in the ratio of urea/creatinine compared with the same BMI population without diabetes risk [33 ± 11.5 vs 38 ± 11.8 Mean ± SD] (P &amp;lt; 0.05). PCA analysis formed four clusters: PC1+ (cluster 1) with increased creatinine (1.9 mg/dL) &amp; urea (63.5 mg/dL) and transition to diabetes; PC2+ (cluster 2) with normal creatinine (0.7 mg/dL) &amp; urea (28.1 mg/dL) and diabetes risk; PC1+PC2+ (cluster 3) with increased creatinine (1.4 mg/dL), increased urea (50.44 mg/dL), and diabetes risk; PC1-PC2- (cluster 4) with normal creatinine (0.7 mg/dL), normal urea (28.7 mg/dL), and transition to diabetes. PCA analysis found that Cluster 1 had a higher urea/creatinine ratio (34.7 ± 10.6 vs 40 ± 12.3, Mean ± SD) compared to Cluster 2 (P &amp;lt; 0.01). Cluster 1 was made up of mostly men (80.5%) with an average age of 54 ± 8.9 years, of which 22% were normal weight and 34.2% were overweight. Cluster 2 had more women (65.10%) with an average age of 47 ± 11.7 years, 20.6% normal weight and 32.6% overweight. A total of 17.9% of overweight individuals with a transition to diabetes risk were found in PC1 (14/78) and 8.1% in PC2 (4/49). Conclusion Urea/creatinine ratio could be a useful indicator of diabetes risk in overweight individuals. PCA selection method identifies diabetes risk indexes for early care management by clinicians.

B-039 Method Performance Evaluation of the Siemens Atellica Cystatin C Assay on the CH930 Instrument

Abstract Background The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease published recommendations on the implementation of the CKD-EPI 2021 equation to calculate eGFRcr without a race coefficient. Clinical practice recommendations also suggest increasing availability of Cystatin C testing which can be a more reliable marker of renal function than creatinine for select adults with eGFRcr near medical decision points and in situations where non-GFR factors may have a large effect on serum creatinine. This study evaluated the method performance characteristics of the Cystatin C assay on the Siemens Atellica CH930 analyzer. The assay measures agglutination of latex particles coated with anti-cystatin C antibody at 571/805 nm and is approved for determination of Cystatin C in serum and plasma (lithium heparin, and EDTA). Methods Cystatin C reagent lot 2114231 and calibrator lot 560956 were used in the study. Intra-run precision was evaluated using BioRad IntelliQ Immunology Control (Level 1 lot 68991, Level 2 lot 68993). Inter-run precision was evaluated over 20 consecutive days. Mean, SD, and CV were calculated and compared to manufacturer precision claims in the IFU and BioRad UNITY™ Interlab Reports. Linearity was evaluated using AUDIT MicroControls Cystatin C Linearity LQ (Lot 06901). Accuracy was evaluated by measuring 40 serum samples on the Atellica CH930 and Roche Diagnostics Tina-Quant Cystatin C Gen 2 assay. Acceptable criteria were defined as a calculated slope between 0.9–1.1 and r greater than 0.995. Appropriateness of the adult reference interval was evaluated with 20 female and 20 male presumably healthy donors. Acceptability was defined as less than 10% of results outside the proposed range. Results Intra-run CV ranged from 2.3–9.2% (Level 1 QC) and 1.2–2.6% (Level 2 QC) across four different CH930 instruments. Level 1 precision did not verify the manufacturer claim of ≤3.6% CV on 3 out of 4 instruments. Level 2 precision did not verify the manufacturer claim of ≤1.7% CV for any instrument tested. Using BioRad UNITY™ peer performance as targets, 3 of 4 instruments had CV ≤6.7% for Level 1 and all instruments had CV ≤2.8% for Level 2. Inter-run precision for Level 1 QC was ≤5.94% CV which was less than the BioRad Peer Group CV. Linearity material spanned 0.490–5.893 mg/L and results were within manufacturer’s expected ranges. Method comparison with the Roche Tina-Quant Gen 2 assay had a calculated slope of 0.954, intercept of 0.094, and r value equal to 0.9993. Thirty-nine of 40 results were within 10% of the reference method (range 0.74–5.45 mg/L). Verification of the reference interval using presumably healthy donors resulted in 5.3% (2/38) of results outside the proposed range. Conclusion With the exception of precision, all other manufacturer-claimed performance specifications for the Siemens Atellica Cystatin C assay were verified using four CH930 instruments at our institution.

FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway.

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), and its pathogenesis is not fully understood. Previously, we showed that fractalkine (FKN) expression was positively correlated with the severity of LN. Here, we aimed to study the role of the Hippo signaling pathway (HSP) and its interaction with FKN in LN in an attempt to provide novel strategies for LN treatment. In this study, lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-stimulated THP-1 cells were co-cultured with FKN up-regulated or down-regulated kidney epithelial cells Hkb20. FKN-knockout (KO-FKN) mice were used to construct LN model. Flow cytometric analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), pathological staining, Western blot, and immunofluorescence (IF) staining were employed to investigate the role of FKN and its interaction with the Hippo signaling pathway (HSP) in LN. Up-regulation of FKN in kidney epithelial cells was associated with increased macrophage activation. FKN overexpression in kidney epithelial cells suppressed apoptosis, inflammation levels, and M1 polarization of THP-1 cells and inhibited the HSP. Oppositely, FKN knockdown in kidney epithelial cells increased apoptosis, inflammation, and M1 polarization and activated the HSP. HSP inhibitor reversed the effect of FKN knockdown on THP-1 cells. In LN mice, FKN knockout and YAP inhibitor decreased the levels of renal function markers, alleviated kidney injury induced by LN, and inhibited macrophage activation in LN mice. FKN down-regulation reduced the activation of macrophages in renal tissue and alleviated kidney damage by activating HSP. The regulatory effect of FKN on HSP should be confirmed in patients with LN, and the mechanism of FKN in LN should be further explored.

Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.

Herpes simplex virus reactivation among severe COVID-19 patients: to treat or not to treat?

Background: Herpes simplex virus type 1 (HSV-1) reactivation in the airways is a common finding among patients admitted to the intensive care unit and has been more recently been reported in critically ill COVID-19 patients. Evidence suggests that HSV-1 reactivation in critically ill patients may be associated with higher morbidity and mortality rates. However, there is conflicting data about whether treatment with acyclovir impacts outcomes. Objectives: The primary aim of this study is to assess whether acyclovir improves survival in critically ill COVID-19 patients with concomitant HSV-1 reactivation. Additionally, we explore the effect of acyclovir on cardiorespiratory instability, biochemical markers of inflammation and renal function. Incidence, potential risk factors and outcomes of HSV-1 reactivation in COVID-19 ICU patients are studied last. Methods: A retrospective single-center cohort study set in a Belgian tertiary-care university hospital. All COVID-19 patients admitted to the ICU between March 1st, 2020, and April 15th, 2021, and were tested for HSV-1 using real-time PCR in airway samples were included for analysis. The administration of acyclovir for patients with HSV-1 reactivation was not randomized. Mortality and various markers of morbidity (cardiorespiratory instability, biochemical markers of inflammation, and renal function) were compared between patients that had received acyclovir and those that had not. Secondary outcome measures were respiratory and inflammatory markers of disease severity. Results: 34.7% (42/121) of patients had HSV-1 reactivation, of which 67% (28/42) received acyclovir. ICU mortality was 36% (n = 10) in the acyclovir group versus 0% in the untreated group. Multivariate analysis resulted in OR 3.82 (95% CI 1.37 – 10.68) for ICU mortality in the treated group. Patients treated with acyclovir had a longer length of stay (41.8 vs. 26.8 days, p = .018), longer duration of invasive mechanical ventilation (33.4 vs. 21.8 days, p = .050), and lower PaO2/FiO2 ratio (59.9 vs. 73.4 mmHg, p = .008). Conclusions: The role of acyclovir in patients with HSV-1 reactivation in the ICU remains controversial. According to this study, respiratory HSV-1 reactivation for this specific patient group might be better left untreated. Treatment selection bias, however, could not be fully excluded.

Correlation of urinary neutrophil gelatinase-associated lipocalin levels as an early diagnostic marker for acute kidney injury in patients with sepsis

Background. The exact association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and acute kidney injury (AKI) is unknown in a critical care setting, in which the population is heterogeneous and the aetiology of AKI is unclear. Aim of this study is to clarify if uNGAL level is an early diagnostic marker for AKI in patients with sepsis. Materials and methods. The current study was conducted on 86 sepsis patients. The prevalence of AKI was identified among them. The role of uNGAL in predicting AKI development, mortality rate and length of the intensive care unit (ICU) stay were analyzed. Sensitivity and specificity were calculated, and the area under the receiver operating characteristic curve was considered as the optimal uNGAL cut-off level for detecting all classifications of AKI. Results. Most patients belonged to the age group of 51–60 years and their mean age was 54.6 years. Most patients (65.11 %) were males. 26.75 % had both type 2 diabetes mellitus and hypertension. AKI was detected in 89 % of subjects in the current study, as per KDIGO definition. 15.12 % of patients had stage 1 CKD, 15.12 % had stage 2 CKD, and stage 3 CKD was diagnosed in 4.65 % of cases. Mortality rate was 11 %, and 89 % of patients were discharged. The mean ICU length of stay among patients with AKI is 8.9 days. There is significant association between the mean ICU length of stay and AKI presence (p = 0.03). 17.4 % (n = 15) of patients required renal replacement therapy. There is a very significant difference in mean baseline uNGAL in patients with and without AKI: 149.9 and 73.2 ng/ml, respectively (p = 0.0006). This indicated that baseline uNGAL levels predict AKI. The mean uNGAL in people with AKI was 356 ng/ml and in those without AKI, it was 95 ng/ml. There is a very significant difference in mean uNGAL 48 hours after in patients with and without AKI (p &lt; 0.0001). At a cut-off value of 120, there were 69 true positive cases, 9 true negative cases, 0 false positive cases, and 8 false negative cases. Based on these, the sensitivity of uNGAL at baseline in detecting AKI is 89.61 %, specificity is 100 %, and accuracy is 90.70 %. At a cut-off point of 120, there were 77 true positive cases, 8 true negative cases, 1 false positive case, and 0 false negative cases. Based on these, the sensitivity of uNGAL 48 hours after was 100 %, specificity 88.89 %, and accuracy was 98.84 %. There is a significant association between uNGAL levels and the ICU length of stay (p = 0.00). Conclusions. Sensitivity analysis was done in cut-off value of 120 for urinary NGAL in predicting AKI. From these results we conclude that urinary NGAL at the time of ICU admission is a reliable marker of renal function in sepsis patients. There is a significant correlation between AKI presence and urinary NGAL, and the ICU length of stay. We recommend not to use uNGAL alone in predicting AKI. It should be combined with glomerular filtration rate to reliably detect AKI development. Study findings indicate that sepsis patients with elevated uNGAL require proper management with close monitoring of blood pressure, urine output and appropriate doses of diuretics to avoid the development of AKI.

Potential Effects of Digoxin on Renal Functions in Patients With Congestive Heart Failure.

Renal dysfunction is a common complication among patients with congestive heart failure (CHF) and can significantly impact their management, especially when medications like digoxin are involved. The clearance of digoxin is closely tied to the glomerular filtration rate (GFR), which suggests that the safety and efficacy of digoxin may vary with renal function. Therefore, this study aimed to assess the potential effects of digoxin on renal function in patients diagnosed with CHF at a tertiary hospital in the Asir region of Saudi Arabia. A retrospective study examined the records of 30 CHF patients treated with digoxin. Renal function markers like estimated GFR (eGFR), creatinine, blood urea nitrogen (BUN), albumin, and urine levels were compared before and after digoxin treatment. Liver enzymes and other relevant parameters were also examined. A statistical analysis using t-tests was conducted to evaluate the changes in renal function indicators before and after digoxin treatment. The mean eGFR decreased significantly from 65.4 ± 8.9 mL/min/1.73m2 before digoxin to 57.7 ± 7.8 mL/min/1.73m2 after (p = 0.001). Creatinine, BUN, albumin, and urine levels showed no significant changes. Digoxin significantly increased aspartate aminotransferase (AST) from 34.5 ± 11.6 U/L to 53.8 ± 14.6 U/L (p = 0.002), alanine aminotransferase (ALT) from 38.5 ± 12.6 U/L to 55.3 ± 17.6 U/L (p = 0.013), and creatine kinase from 117.7 ± 22.5 U/L to 133.9 ± 15.8 U/L (p = 0.012). Hemoglobin decreased significantly from 12.8 ± 1.4 g/dL to 12.1 ± 1.4 g/dL (p = 0.034). No significant changes occurred in myoglobin, troponin, bilirubin, platelets, potassium, calcium, or chloride levels. Effects on kidney function did not differ significantly by gender or age, except blood urea nitrogen was higher in patients over 50 years (8.3 ± 2.3 vs. 5.6 ± 2.7 mg/dL, p = 0.015). This study suggests digoxin may adversely affect renal function in CHF patients, as evidenced by reduced eGFR. However, the small retrospective design limits definitive conclusions. Further prospective research with larger samples is warranted to elucidate digoxin's renal effects in CHF patients.

Safety Assessment and Hepatic-Renal Protection of Cajanus cajan (L.) Millsp. Root and Its Soy Isoflavone Contents.

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.

Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice

ObjectiveTo investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). MethodsA total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. ResultsAge-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). ConclusionMetabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

Cardiorenal syndrome and iron supplementation-more benefits than risks: a narrative review.

Intravenous iron administration has emerged as a crucial intervention for managing patients with cardiorenal syndrome (CRS) and iron deficiency, with or without the presence of anemia. Multiple studies have demonstrated the benefits of intravenous iron supplementation in improving anemia, symptoms, and functional capacity in patients with HF and iron deficiency. Furthermore, iron supplementation has been associated with a reduction in hospitalizations for HF exacerbation and the improvement of patients' quality of life and clinical outcomes. In addition to its effects on HF management, emerging evidence suggests a potential positive impact on kidney function in patients with CRS. Studies have shown an increase in estimated glomerular filtration rate and improvements in renal function markers in patients receiving intravenous iron therapy, highlighting the potential of this intervention in patients with CRS. This paper reviews the existing literature on the impact of intravenous iron therapy in these patient populations and explores its effects on various clinical outcomes. Future research endeavors are eagerly awaited to further improve our understanding of its clinical implications and optimize patient outcomes.

Cinacalcet in patients with primary hyperparathyroidism; a review

Primary hyperparathyroidism (PHPT) is a condition characterized by the parathyroid glands’ overproduction of parathyroid hormone (PTH). These increases calcium levels in the blood, leading to various symptoms and complications. Cinacalcet is a promising therapeutic option for patients with PHPT who are unable or unwilling to undergo surgery. It effectively reduces serum calcium and PTH levels, improving biochemical markers of bone turnover and renal function. However, more research is needed to determine the optimal dosage, duration, and long-term effects of cinacalcet treatment in this patient population. Clinicians should carefully consider the risks and benefits of cinacalcet therapy individually and involve patients in shared decision-making.

Assessment of the Effects of Garlic-Citrus-Tumeric Shot on Bilirubin, Alkaline Phosphatase and Transaminases Levels

Medicinal plants are widely used in disease management all over the world. Plant-based traditional medicines are still of great importance to people living in developing countries and also serve as a source to discover new drugs for a variety of diseases affecting man. The aim of this study is to investigate the effect of garlic-citrus-tumeric shot on bilirubin, ALP, ALT and AST of adult albino wistar rats. The animals were divided into two groups; the control group and the experimental animals. A total of five (5) adult wistar rats were used for the control group, while fifteen (15) adult wistar rats were used for the experimental studies. During the period of acclimatization, the rats were fed growers’ mash water provided ad libitum. At every stage of the weight determinations, the test groups (B, C and D) presented body weight reductions. Body weights were found to be significantly increased in the control and tests groups before and after acclimatization. However, variations in body reductions were observed between the control and test rats. Comparatively, these body weight variations were significant in group C (175.00±0.01 g) and D (171.67±24.83 g) after garlic-citrus-tumeric shot administration. The results showed that AST levels were significantly lower (p&lt;0.05) in rats (23.73±7.93 U/L) when compared with the control (33.60±6.23 U/L). Also, ALT levels were significantly lower (p&lt;0.05) in rats (19.67±7.58 U/L) when compared with the control (28.40±5.18 U/L). ALP levels were also lower (p&lt;0.05) in rats (17.13±5.36 U/L) when compared with the control (24.80±4.15 U/L). Furthermore, TB levels were also significantly lower (p&lt;0.05) in rats (0.38±0.14 mg/dl) when compared with the control (0.80±0.16 mg/dl). Also, CB levels were significantly lower (p&lt;0.05) in rats (0.21±0.11 mg/dl) when compared with the control (0.38±0.08 mg/dl). Garlic-citrus-tumeric shot inhibits elevations of biochemical markers of hepatic and renal functions. This suggests that combination of garlic-citrus-tumeric shot is not toxic to the liver. Conclusively, the increase in extract given to adult wister rat decreases the parameters of liver function test thereby increases liver normalcy or better the performance state of the liver, hence, when the extract is taking in the right proportion increases the performance of the liver.

Maternal Di-(2-Ethylhexyl) Phthalate (DEHP) Exposure Impairs Insulin Signal in the Liver and Gastrocnemius Muscles of Female Offspring Rats

Di-(2-Ethylhexyl) Phthalate (DEHP) is a potent endocrine disruptor that is commonly present in consumer products and cosmetics. Exposure to DEHP during gestational and lactational periods can adversely affect glucoregulation and lead to the onset of diabetes in progeny. The liver and gastrocnemius muscles play an important role in regulating glucose metabolism and insulin action. This study was designed to investigate the effect of maternal DEHP exposure on insulin signaling molecules in the liver and gastrocnemius muscles of adult female offspring rats. Rat dams were given DEHP (10 and 100 mg/kg b.wt./day) by oral gavage from gestation day 9 (GD 9) to the end of the lactation period Postnatal Day (PND) 21. On PND 80, female offspring rats in diestrus were euthanized and found reduced body weight, organ (liver and gastrocnemius) weight, and hyperglycemia in DEHP-exposed rats. Western blots revealed a dose-dependent reduction in the expression of Insulin Receptor - (IR), IRS, Akt, and GSK-3β proteins as well as their phosphorylated forms in the liver and gastrocnemius muscles of DEHP-exposed offspring rats. Maternal DEHP exposure reduced the levels of GLUT2 and GLUT4 level in the liver and gastrocnemius muscles, respectively. Liver and renal function markers were dose-dependently increased in the serum of offspring female rats born to DEHP exposed mother during gestation and lactation. Thus, the study revealed that maternal DEHP exposure impaired the expression of insulin signaling molecules in the two important tissues involved in glucose metabolism, the liver and gastrocnemius muscles, suggesting that phthalates exposure during development may contribute to the onset of diabetes in female offspring.

Phytochemical study and Protective Effect of Trigonella foenum-graecum (Fenugreek Seeds) Methanolic Extract Underlying the Mechanism of Action on Diabetic Nephropathy in Experimental Rats

Background: Advanced glycation end products (AGEs) buildup and hyperglycemia both contribute significantly to the onset of diabetic nephropathy. A plant with high flavonoid content, Fenugreek Seeds Extract (FSE), may be able to reduce the activity of oxidative stress in cells and tissues. The purpose of this study was to determine if Fenugreek Seeds Extract (FSE) could prevent kidney damage in diabetic rats caused by the production of AGEs in the renal glomerulus. Objective: The current study aimed to estimate phytochemical screening, in-vitro antioxidant activity, and nephron-protective effect of Trigonella foenum-graecum (Fenugreek Seeds) methanolic extract. Methods: We have demonstrated the phytochemical composition of extract of fenugreek seeds. The antioxidant activity of the extract was determined using DPPH assay. Total of thirty six albino wistar rats were used for diabetic nephropthic activity. Normal control rats and diabetic rats were given low doses of fenugreek seed extract (100 mg/kg), medium doses (200 mg/kg), and high doses (400 mg/kg) by oral gavage for 8 weeks before being put to sacrificed. Adiponectin, renal function markers, pro-inflammatory markers, antioxidative markers, and glucose concentration were all measured. Results: It has been found that FSE treatment significantly prevented in STZ-induced increases in urine production, urinary albumin excretion, and urine albumin-to-creatinine ratio and markedly attenuated STZ-induced renal damages. Levels of aspartate aminotransferase, alanine aminotransferase and serum creatinine, blood urea nitrogen and malondialdehyde of kidney tissue were lower in extract treated groups than in contrast agent treated group, but the decrease in serum MDA was significant in the group given FSE. Serum antioxidant capacity was higher in the FSE contrast agent group than in the contrast agent group. Kidney tissue anti-oxidant capacity was significantly higher in the group given FSE than the contrast agent group. Conclusion: This study demonstrated that an appropriate amount of FSE 200 mg/kg in rats, could prevent diabetic nephropathy by improving antioxidant status and inhibiting inflammation in renal tissue. FSE extract may be effective in treating high-glucose-induced nephropathy.

Physiological Effects of Fig Leaf Extract and Orlistat on Obesity, Kidney and Liver of Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; Obesity is a global health epidemic associated with various health complications. This study investigates the potential effects of ethanolic fig leaf extract and orlistat on obesity, as well as their impact on kidney and liver function in a rat model, aiming to contribute to the development of strategies for managing obesity-related health issues. &lt;b&gt;Materials and Methods:&lt;/b&gt; Forty male albino rats with hypercholesterolemia were divided into four groups: Group one served as a control and received a normal diet, group two was a control group that was fed a high-fat diet, group three received a high-fat diet with a daily force-fed ration of 3 g kg&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; b.wt., of fig leaves and group four received a high-fat diet along with daily administration of orlistat at 4 mg kg&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; b.wt. Blood samples were collected from all groups at baseline and after 30 days of treatment. &lt;b&gt;Results:&lt;/b&gt; Rats in the high-fat diet group showed a significant increase in body weight by 49%, while rats treated with fig leaf extract showed a significant decrease in body weight by 18% (p<0 .01) and treatment with orlistat resulted in 12% elevation in body weight. Renal function markers creatinine and urea were decreased in the group treated with fig leaves. Liver enzymes AST, ALT and ALP decreased significantly in the group treated with fig leaves and orlistat. Albumin and globulin concentrations decreased more with fig leaf extract than with orlistat. &lt;b&gt;Conclusion:&lt;/b&gt; Fig leaves and orlistat reduce body weight and improve kidney and liver function in hypercholesterolemic rats.

Real-time laser speckle contrast imaging measurement during normothermic machine perfusion in pretransplant kidney assessment.

Normothermic machine perfusion (NMP) provides a platform for pre-transplant kidney quality assessment that is essential for the use of marginal donor kidneys. Laser speckle contrast imaging (LSCI) presents distinct advantages as a real-time and noncontact imaging technique for measuring microcirculation. In this study, we aimed to assess the value of LSCI in visualizing renal cortical perfusion and investigate the additional value of dual-side LSCI measurements compared to single aspect measurement during NMP. Porcine kidneys were obtained from a slaughterhouse and then underwent NMP. LSCI was used to measure one-sided cortical perfusion in the first 100 min of NMP. Thereafter, the inferior renal artery branch was occluded to induce partial ischemia and LSCI measurements on both ventral and dorsal sides were performed. LSCI fluxes correlated linearly with the renal blood flow (R2 = 0.90, p < 0.001). After renal artery branch occlusion, absence of renal cortical perfusion could be visualized and semiquantified by LSCI. The overall ischemic area percentage of the ventral and dorsal sides was comparable (medianinterquartile range[IQR], 38 [24-43]% vs. 29 [17-46]%, p = 0.43), but heterogenous patterns between the two aspects were observed. There was a significant difference in oxygen consumption (mean ± standard deviation [SD], 2.57 ± 0.63 vs. 1.83 ± 0.49 mLO2 /min/100 g, p < 0.001), urine output (median [IQR], 1.3 [1.1-1.7] vs. 0.8 [0.6-1.3] mL/min, p < 0.05), lactate dehydrogenase (mean ± SD, 768 ± 370 vs. 905 ± 401 U/L, p < 0.05) and AST (mean ± SD, 352 ± 285 vs. 462 ± 383 U/L, p < 0.01) before and after renal artery occlusion, while no significant difference was found in creatinine clearance, fractional excretion of sodium, total sodium reabsorption and histological damage. LSCI fluxes correlated linearly with renal blood flow during NMP. Renal cortical microcirculation and absent perfusion can be visualized and semiquantified by LSCI. It provides a relative understanding of perfusion levels, allowing for a qualitative comparison between regions in the kidney. Dual-side LSCI measurements are of added value compared to single aspect measurement and renal function markers.

Podocin, mTOR, and CHOP dysregulation contributes to nephrotoxicity induced of lipopolysaccharide/diclofenac combination in rats: Curcumin and silymarin could afford protective effect

AimSepsis is a common cause of acute kidney injury (AKI). Lipopolysaccharides (LPS) are the main gram-negative bacterial cell wall component with a well-documented inflammatory impact. Diclofenac (DIC) is a non-steroidal anti-inflammatory drug with a potential nephrotoxic effect. Curcumin (CUR) and silymarin (SY) are natural products with a wide range of pharmacological activities, including antioxidant and anti-inflammatory ones. The objective of this study was to examine the protective impact of CUR and SY against kidney damage induced by LPS/DIC co-exposure. Materials and methodsFour groups of rats were used; control; LPS/DIC, LPS/DIC + CUR, and LPS/DIC + SY group. LPS/DIC combination induced renal injury at an LPS dose much lower than a nephrotoxic one. Key findingNephrotoxicity was confirmed by histopathological examination and significant elevation of renal function markers. LPS/DIC induced oxidative stress in renal tissues, evidenced by decreasing reduced glutathione and superoxide dismutase, and increasing lipid peroxidation. Inflammatory response of LPS/DIC was associated with a significant increase of renal IL-1β and TNF-α. Treatment with either CUR or SY shifted measured parameters to the opposite side. Moreover, LPS/DIC exposure was associated with upregulation of mTOR and endoplasmic reticulum stress protein (CHOP) and downregulation of podocin These effects were accompanied by reduced gene expression of cystatin C and KIM-1. CUR and SY ameliorated LPS/DIC effect on the aforementioned genes and protein significantly. SignificanceThis study confirms the potential nephrotoxicity; mechanisms include upregulation of mTOR, CHOP, cystatin C, and KIM-1 and downregulation of podocin. Moreover, both CUR and SY are promising nephroprotective products against LPS/DIC co-exposure.