Kidney Markers Research Articles

Zinc pretreatment for protection against intestinal ischemia-reperfusion injury.

Intestinal ischemia-reperfusion (I/R) injury (II/RI) is a critical condition that results in oxidative stress, inflammation, and damage to multiple organs. Zinc, an essential trace element, offers protective benefits in several tissues during I/R injury, but its effects on intestinal II/RI remain unclear. To investigate the effects of zinc pretreatment on II/RI and associated multiorgan damage. C57BL/6 mice were pretreated with zinc sulfate (ZnSO4, 10 mg/kg) daily for three days before I/R injury was induced via superior mesenteric artery occlusion (SMAO) and abdominal aortic occlusion (AAO) models. Tissue and serum samples were collected to evaluate intestinal, liver, and kidney damage using Chiu's score, Suzuki score, and histopathological analysis. Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models (P < 0.001). The serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase) and kidney markers (creatinine and urea) were lower in the zinc-treated mice than in the control mice, indicating reduced hepatic and renal injury. In vitro, zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury. Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls. Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage. These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.

Assessing the quality of CKD care using process quality indicators: A scoping review.

Assessing the quality of chronic kidney disease (CKD) management is crucial for optimal care and identifying care gaps. It is largely unknown which quality indicators have been widely used and the potential variations in the quality of CKD care. We sought to summarize process quality indicators for CKD and assess the quality of CKD care. We searched databases including Medline (Ovid), PubMed, Cochrane Library, Web of Science, CINAHL, and Scopus from inception to June 20, 2024. Two reviewers screened the identified records, extracted relevant data, and classified categories and themes of quality indicators. We included 24 studies, extracted 30 quality indicators, and classified them into three categories with nine themes. The three categories included laboratory measures and monitoring of CKD progression and/or complications (monitoring of kidney markers, CKD mineral and bone disorder, anemia and malnutrition, electrolytes, and volume), use of guideline-recommended therapeutic agents (use of medications), and attainment of therapeutic targets (blood pressure, glycemia, and lipids). Among the frequently reported quality indicators (in five or more studies), the following have a median proportion of study participants achieving that quality indicator exceeding 50%: monitoring of kidney markers (Scr/eGFR), use of medications (ACEIs/ARBs, avoiding non-steroidal anti-inflammatory drugs (NSAIDs)), management of blood pressure (with a target of ≤140/90, or without specific targets), and monitoring for glycated hemoglobin A1c (HbA1c)). The presence of diabetes, hypertension, cardiovascular disease, or proteinuria was associated with higher achievement in indicators of monitoring of kidney markers, use of recommended medications, and management of blood pressure and glycemia. The quality of CKD management varies with quality indicators. A more consistent and complete reporting of key quality indicators is needed for future studies assessing CKD care quality.

Vanadium exposure and kidney markers in a pediatric population: a cross-sectional study.

Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed. A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin-creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders. Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile. Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.

Diphenyl diselenide protects against diabetic kidney disease through modulating gut microbiota dysbiosis in streptozotocin-induced diabetic rats.

Diphenyl diselenide (DPDS) ameliorates nephropathy in streptozotocin (STZ)-induced type 1 diabetic rats by inhibiting oxidative stress and inflammatory reactions. However, it has not been clarified whether DPDS alleviates type 1 diabetic kidney disease (DKD) is related to the inhibition of extracellular matrix (ECM) production and the regulation of intestinal flora disorder. The present study investigated the effects of DPDS on ECM generation in the kidney and intestinal microflora composition in feces. The rats were orally administered DPDS or metformin for eight weeks. Various indices were measured to assess the severity of renal injury. After euthanizing the rats, oxidative stress markers in serum and kidney were assessed using biochemical methods, and the expressions of ECM-related proteins in kidney were analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora in feces. The results showed DPDS and metformin improved the DKD in STZ rats, as evidenced by decreased blood glucose, BUN, urine volume, urine microalbumin, urinary β2 microglobulin, and improvement of renal pathological morphology. Furthermore, DPDS intervention markedly reduced the protein expression of α-SMA, COI Ⅳ, FN, and vimentin in the kidneys. Besides, DPDS not only improved dyslipidemia in STZ diabetic rats, but also enhanced the activities of antioxidant enzymes, decreased the level of MDA in serum and kidney, and regulated the expression of proteins related to the Nrf2/Keap1 signaling pathway in the kidney. Moreover, we found that DPDS could selectively improve the relative abundance of probiotics as well as the diversity of flora, thus ameliorating the intestinal microbial composition of the STZ rats, significantly regulating the intestinal microbial homeostasis. Overall, DPDS inhibited ECM production and improved renal pathological changes, which may be related to reducing oxidative stress damage in the kidney and improving intestinal flora imbalance, providing data support for the further development and application of DPDS in DKD.

Monitoring of liver and kidney profiles in anesthesiologists working in a regional reference teaching hospital in Northern Italy: analysis of health surveillance data using a linear mixed model.

Anesthesiologists represent an occupational group exposed to specific occupational hazards, including potential exposure to waste anesthetic gas released during medical procedures. In recent decades, halogenated anesthetic gases, such as desflurane and sevoflurane, have largely replaced nitrous oxide, due to better safety profiles and lower adverse health effects. However, possible long-term effects of low concentration exposures are unknown. A longitudinal analysis of health surveillance data was performed to test for possible changes over time in key markers of liver and kidney function. Moreover, we assessed the appropriateness of applying linear mixed models to occupational health data. A retrospective cohort study was conducted using health surveillance data from a cohort of anesthesiologists and a cohort of unexposed physicians working at the Polyclinic Hospital San Martino of Genoa, Italy, during 2016-2022. A 2-level linear mixed model with covariance structure of first order autoregressive model (AR(1)) type at the first level and unstructured type at the second level was applied. One hundred seventy subjects were included in the analysis, equally divided between exposed and unexposed. At the first and last periodic examination, liver and kidney markers were not statistically different in the 2 cohorts. The only significant change found related to estimated glomerular filtrate, which was found at the last follow-up to be greater among the exposed (M = 104.18 vs. 90.07, p = 0.007). The linear mixed model showed that anesthetic gas exposure was not associated with any of the outcomes. These results suggest the absence of increase in liver and kidney profile markers in the study population. Health surveillance data, aggregated and analyzed with appropriate statistical models, allow inferences to be made about potential health effects of workers due to uncontrolled exposures. To this end, the linear mixed model represents a powerful tool for longitudinal analysis of data derived from monitoring workers. Int J Occup Med Environ Health. 2024;37(5).

Network pharmacology combined with transcriptomics reveals that formononetin, a biologically component of Astragalus membranaceus (Fisch.) Bunge, inhibits the PI3K/AKT signaling pathway to improve chronic renal failure

Ethnopharmacological relevanceFormononetin (FMN), one of the main isoflavones isolated from Astragalus membranaceus (Fisch.) Bunge, has multiple pharmacological and renal-protective effects. Our previous study suggested FMN as a candidate compound for the treatment of chronic renal failure (CRF). However, the mechanism underlying the repressive effect of FMN on the development of CRF is still unknown. Aims of the studyTo investigate the protective effect of FMN on CRF using in vivo and in vitro models and elucidate the potential underlying mechanism. Materials and methodsAn in vivo model of adenine-induced CRF and an in vitro model of human proximal tubule epithelial cells (HK-2) stimulated with transforming growth factor (TGF)-β1 were used. Serum levels of renal function parameters and inflammatory cytokines were evaluated. Histological analysis was performed to determine the extent of renal injury and fibrosis. Network pharmacology and mRNA sequencing were used to explore the potential mechanism. PPI analysis and molecular docking were used to identify key targets. Polymerase chain reaction and western blotting were used to determine the mechanism underlying the effect of FMN on CRF. ResultsFMN decreased the levels of renal function biochemical markers, including serum creatinine, blood urea nitrogen, and 24 h urine protein content. Treatment with FMN improved renal tubule injury and extracellular matrix (ECM) components, including collagens I and III. In addition, FMN significantly inhibited epithelial-mesenchymal transition (EMT); decreased the expression of fibronectin, N-cadherin, vimentin, α-SMA, and TGF-β1; and restored the expression of E-cadherin. The effect of FMN on renal interstitial fibrosis contributed to decreasing the expression of PI3K, p-Akt, and interleukin (IL) 4, restoring the expression of nitric oxide synthase 3 (NOS3), and reducing the release of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-alpha), both in vivo and in vitro. FMN treatment improved renal function and deposition of ECM components, reduced protein levels of EMT markers in rat kidneys and HK-2 cells, decreased the release of inflammatory cytokines, and inhibited the PI3K/Akt signaling pathway. ConclusionsFMN treatment significantly reduced the release of inflammatory cytokines and inhibited the effects of the PI3K/Akt signaling pathway on the key targets IL-4 and NOS3. Our results suggest FMN therapy as a novel therapeutic strategy for treating CRF.

Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice

The present study was carried out to evaluate and compare the protective potential of two well-known antioxidants of herbal origin in a mouse model of acute DIC-induced nephro- and hepatotoxicity. The tested antioxidants included lemongrass essential oil (LO) and its predominant bioactive constituent citral (CIT). A third herbal product, silymarin (SILY), was used as a reference hepato-renal protective agent. DIC administration led to elevated serum urea and creatinine levels, and prompted oxidative stress along with histopathological changes in the kidney tissue. In parallel, DIC administration increased serum liver enzyme activity, decreased total protein, albumin, and globulin levels, and caused oxidative stress with associated histopathological changes in the liver tissue. Pre-treatment with LO or CIT mitigated DIC-induced alterations in all serum biochemical markers of kidney and liver health (except albumin). High-dose LO, like SILY, within kidney and liver tissues, counteracted DIC-induced oxidative stress and histomorphological alterations. By contrast, CIT failed to mitigate DIC-induced oxidative stress in the kidneys and provided only partial control of DIC-induced oxidative stress in the liver, resulting in less efficient preservation of kidney function and liver structural integrity than LO. Besides confirming the efficacy of SILY at protecting kidneys and liver against the toxicity of DIC in a rodent species different from the one tested so far (rat), this study demonstrated the preventive properties of LO and, to a lesser extent, of CIT against DIC-induced hepato-renal toxicity in mice, supporting their developmental potential as therapeutics.

Analysis of angiotensin II type 1 receptor and osteoprotegerin gene polymorphism on the risk of cardiovascular mortality risk and progressivity of chronic kidney disease.

Chronic kidney disease (CKD) is a significant global public health issue with increased risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality. Single nucleotide polymorphisms (SNPs) on angiotensin II type 1 receptor (AT1R) A1166C and osteoprotegerin (OPG) C950T gene have received significant attention as a genetic risk factor for cardiovascular disease and CKD. This was a cross-sectional study involving 75 adults with CKD recruited from Nephrology Outpatient Clinics of Universitas Airlangga Hospital, Surabaya, Indonesia. Demographic data was obtained from interviews and medical records. The "CKD Patch" application was used to asses ASCVD and cardiovascular mortality risk scores. Statistical analysis was performed by using SPSS version 26. We detected four different AT1R gene polymorphisms (A1166C, A1160C, G1170T, and G1181C) and two OPG gene polymorphisms (T950C and G1181C) in Indonesian CKD patients. A1160C and G1181C polymorphisms were novel SNPs, newly discovered in this research. No significant association was found between AT1R SNPs and kidney prognostic markers or ASCVD risk/mortality risk scores. However, for OPG C950T we found that TT genotype had a significantly higher ACR than TC or CC genotype (P=0.032). As for OPG G1181C, we found that GG genotype had a higher serum creatinine and albumin to creatinine ratio compared to GC and CC genotypes (P=0.004 and 0.029, respectively). Genotype GC for OPG G1181C was also shown to be protective for having better kidney markers and lowest cardiovascular mortality risk compared to GG and CC genotypes (P=0.018 and 0.032, respectively). Increased ASCVD risk and mortality risk score was not found on individuals with AT1R gene SNPs. However, for OPG gene polymorphism, C950T and G1181C were associated with kidney progression and cardiovascular mortality.

Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance

BackgroundChildren with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors.MethodCMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors.ResultsCardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1–2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (β = −0.425, P = 0.019) and LVRI (β = −0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (β = 0.429, P = 0.022). In the CKD stage 3–5 group, higher in systolic blood pressure (SBP) (β = 0.464, P = 0.005) and PCR (β = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3–5 group with hypertension than those without.ConclusionCardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3–5. Strict BP control may help reverse or prevent remodeling.

Association of IgG Glycosylation with Kidney Markers and CKD Progression

Association of IgG Glycosylation with Kidney Markers and CKD Progression

Concentration of kidney markers and detection of exosomes in urine samples collected in cotton wool balls in preterm and term neonates

Collecting urine samples in neonates by catheterisation or suprapubic puncture causes trauma, whereas self-adhesive collection bags can damage fragile skin. An alternative method is the collection of samples from urine-soaked cotton wool balls placed in diapers. The aim of this study was to compare the concentration of albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and uromodulin between clean-catch urine and samples collected in cotton wool balls in neonates and assess the efficiency of exosome extraction. Standard clean-catch urine samples were assayed for albumin, creatinine, NGAL, and uromodulin using commercial enzyme-linked immunosorbent assay (ELISA) kits. Concentrations were compared to the same urine samples extracted immediately from soaked cotton wool balls (sample 2, S2) or the urine extracted from cotton wool balls placed in a diaper in a warm incubator for 2 h before extraction (sample 3, S3). Exosomes were extracted from all three samples of one patient for visualisation by electron microscopy. Twenty-six infants (17 males) of median gestational age at birth of 32+1 weeks had urine collected at a median age of 29 days at 37+6 weeks corrected age. Concentrations in S2 and S3 were within 10% of the concentration of standard samples in 46% and 35% of specimens for albumin, 69% and 58% for creatinine, 12% and 12% for NGAL, and 27% and 15% for uromodulin, respectively, without consistent positive or negative bias. Urine albumin/creatinine ratios (UACRs) were 4.3% less in S2 and 4.5% less in S3 than in standard samples. Exosomes were extracted and visualised from all three sample types. Neonatal urine samples extracted from cotton wool balls can be used to screen for relevant albuminuria ​but provide imprecise estimates of NGAL and uromodulin. The proof of exosome extraction from urine collection in cotton wool balls opens the potential to examine exosomal cargo.

Impact of Fresh Khat Extract on Proinflammatory Cytokines and Hepatic and Renal Responses.

BACKGROUND This study examined the effects of khat extract on the proinflammatory cytokines, liver, and kidneys of rats. Unlike previous research that focused on broad immune markers and general effects, this study investigated specific proinflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, and TNF-alpha) and considered gender differences in the immune response. Fresh khat plants and nontoxic doses were used to obtain clear observations relevant to human health. MATERIAL AND METHODS Extracts were prepared from young shoots of khat plants and fresh leaves. 150-gram male and female rats were randomly divided into 8 groups (5 rats per group). Six groups received the extract orally for 8 weeks at doses of 100, 300, and 500 mg/kg/day. Blood samples were collected after 56 days and assayed for cytokines using ELISA, while liver enzymes and kidney markers were assayed using kinetics and colorimetric methods. RESULTS Khat extract increased the levels of most cytokines, with higher doses causing greater increase. This effect was consistent across sexes for some cytokines (IL-1ß, IL-2), but not others (IL-4, IL-6, TNF-alpha), where sex played a role at specific doses. Various doses of the extract influenced glucose levels in both male and female rats. In addition, liver enzyme markers showed some variations. CONCLUSIONS This study, with its intriguing findings, illuminates the complex effects of khat on various systems. Variations in AST and ALT levels in the liver support earlier hepatotoxicity research and suggest possible khat-induced damage. This study revealed consistently increased levels of all cytokines as the dose of khat extract increased.

The Impact of The Preventive Role of Star Anise on The Toxicity of Benzopyrene Compound in The Liver and Kidney Tissues and Biochemical Parameters in Male Rats

Objective: This study, conducted at the University of Anbar's College of Pure Science, evaluated the protective effects of star anise against benzopyrene (B[a]P)-induced liver and kidney damage in 30 male white Swiss rats (Sprague Dawley), aged 3-4 months and weighing between 170-210 g. Materials and methods: The rats were divided into six groups: Control (G1), B[a]P (G2), Star Anise 125 mg/kg bw (G3), Star Anise 120 mg/kg bw + B[a]P (G4), Star Anise 125 mg/kg bw + B[a]P (G5), and Star Anise 130 mg/kg bw + B[a]P (G6). Results:Biochemical analyses showed that B[a]P exposure significantly elevated liver enzymes (ALP, AST, ALT, GGT) and kidney markers (uric acid, creatinine), indicating hepatic and renal damage. Treatment with star anise, especially 130 mg/kg bw significantly reversed these elevated levels because it protected against the injury. Histopathology showed that the liver and kidney were severely damaged in the B[a]P group and in the star-anise-treated group, normal tissue architecture was well preserved only in high doses of star anise treatment. Conclusion:These outcomes suggest the use of star anise as a hepatoprotective as well as a nephroprotective agent, and this needs to be further strengthened by understanding its mechanisms and long-term effectiveness.

Enhanced Creatinine Level in Diabetic Patients Maximizing the Possibilities of Nephropathy and Its Association With Blood Urea Nitrogen and Glomerular Filtration Rate.

Diabetes mellitusis a common metabolic disorder that is sometimes responsible for kidney diseases, especially in the form of diabetic nephropathy. In this study, we tried to investigate the markers associated with kidney diseases within diabetic patients as compared to non-diabetic participants. In this study, among 237 participants, 81 patients were diabetic, whereas 156 were non-diabetic participants. The level and association of serum creatinine, blood urea nitrogen (BUN), and glomerular filtration rate (GFR) were investigated using the enzymatic method and CKD-EPI equation respectively. We found significantly higher creatinine and BUN levels and lower GFR in the diabetic group compared to the non-diabetic group. Besides, we determined a positive association between creatinine and BUN, and an inverse relationship between GFR and creatinine and BUN respectively which was highly scattered in the case as compared to the non-diabetic group. Further analysis of the participants with high creatinine levels only supported the main outcomes. Conclusion: Our investigation of kidney markers suggests a significant association between diabetes and kidney complications. Leading a healthy lifestyle and maintaining blood sugar and pressure may help to slow down the progress of diabetic nephropathy for diabetic patients.

Hesperidin &amp; Apigenin Attenuates Diabetes &amp; Lipid Levels in Experimentally Induced Diabetes Mellitus in Wistar Rats.

The aim of the present investigation is to study the antidiabetic potential of Hesperidin and Apigenin in Diabetic rats. Wistar Albino rats of either sex (150 to 200 g) were purchased from the CPCSEA approved vendor New Delhi. A total of three animals were used, which received a single oral dose in 500 mg/kg, body weight of different flavonoids. Doses equivalent to 25 mg and 50 mg per kilogram body weight were calculated, and suspended in 1% w/v Tween 80 solutions for the experiment. For OGTT, Different doses of both flavonoids i.e. Hesperidin &amp; Apigenin were administered 60 min prior to oral glucose load (2.0 g/kg). Diabetes was induced in overnight fasted rats by Streptozotocin (60 mg/kg), 15 min. after the i.p. administration of Nicotinamide (120mg/kg). Streptozotocin was dissolved in citrate buffer (0.1 M, pH 4.5) &amp; nicotinamide was dissolved in normal saline. During the study period of 21 days, animals was weighed at 0, 7, 14 and 21 day and effect of vehicle, standard drug and all solvent fractions on body weight was determined. Blood samples was collected by cardiac puncture and retroorbital plexus method into EDTA sprinkled tubes and centrifuged at 3000 rpm for 20 min. Serum was separated as supernatant and stored at -20°C until analysis performed. The biochemical parameters, namely hemoglobin, urea, creatinine, total protein, total cholesterol, triglycerides, HDL determined. The other biochemical tests were performed using kits from Erba Diagnostics. Hesperidin and Apigenin significantly prevented the increase in blood glucose levels after 60 min. of glucose administration at the doses of 25 and 50 mg/kg. After 21 days blood samples were collected by retro-orbital plexus under mild anesthesia. Diabetic control group with no drug treatment showed no significant difference in the fasting serum glucose level after 21 days treatment as compared to the initial day treatment. Hesperidin &amp; Apigenin (25 mg/kg &amp; 50 mg/kg) treated diabetic rat showed a significant (p &lt; 0.05) increase in body weight. The diabetic rat treated with glibenclaimide (10mg/kg) showed gradual and consistent increase in body weight. Treated diabetic rat with Hesperidin &amp; Apigenin showed significant fall in total cholesterol, triglycerides, HDL-C, LDL-C and VLDL-C level at dose of 25 and 50 mg/kg. The Hesperidin and Apigenin had the antidiabetic activity with effects on lipids and other kidney markers..

Sex-specific modulation of renal epigenetic and injury markers in aging kidney.

Sex differences in renal physiology and pathophysiology are now well established in rodent models and in humans. Epigenetic programming is known to be a critical component of renal injury, as studied mainly in male rodent models; however, not much is known about the impact of biological sex and age on the kidney epigenome. We sought to determine the influence of biological sex and age on renal epigenetic and injury markers, using male and female mice at 4 mo (4M; young), 12 mo (12M), and 24 mo (24M; aged) of age. Females had a significant increase in kidney and body weights and serum creatinine levels and a decrease in serum albumin levels from 4M to 24M of age, whereas minor changes were observed in male mice. Kidney injury molecule-1 levels in serum and renal tissue greatly enhanced from 12M to 24M in both males and females. Circulating histone 3 (H3; damage-associated molecular pattern molecules) levels extensively increased with age; however, males had higher levels than females. Overall, females had markedly high histone acetyltransferase (HAT) activity than age-matched males. Aged mice had decreased HAT activity and increased histone deacetylase activity than sex-matched 12M mice. Aged females had substantially decreased renal H3 methylation at lysine 9 and 27 and histone methyltransferase (HMT) activity than aged male mice. Antiaging protein Klotho levels were significantly higher in young males than age-matched females and decreased substantially with age in males, whereas epigenetic repressor of Klotho, trimethylated H3K27, and its HMT enzyme, enhancer of zeste homolog 2, increased consistently with age in both sexes. Moreover, nuclear translocation and activity of proinflammatory transcription factor nuclear factor-κB (p65) were significantly higher in aged mice. Taken together, our data suggest that renal aging lies in a range between normal and diseased kidneys but may differ between female and male mice, highlighting sex-related differences in the aging process.NEW & NOTEWORTHY Although there is evidence of sex-specific differences in kidney diseases, most preclinical studies have used male rodent models. The clinical data on renal injury have typically not been stratified by sex. Our findings provide convincing evidence of sex-specific differences in age-regulated epigenetic alterations and renal injury markers. This study highlights the importance of including both sexes for better realization of underlying sex differences in signaling mechanisms of aging-related renal pathophysiology.

CYSTOCENTESIS AND URINALYSIS IN ZOOMEDICINE: AN UNDERESTIMATED TOOL FOR LARGE FELID STANDARD HEALTH CHECKS.

Chronic kidney disease (CKD) is a prevalent disease among felids; yet its origin is still poorly understood, and the disease often remains asymptomatic for years, underscoring the need for early diagnosis. This study aimed to investigate the diagnostic value of urinalysis in accurately staging CKD, particularly as routine health checks in large felids often overlook its significance. In this research, ultrasound-guided cystocentesis (UGC) was performed on 50 captive nondomestic felids during routine veterinary health checks under general anesthesia. Urinalysis included microscopic examination of the sediment, measurement of urine specific gravity (USG) and protein to creatinine ratio (UPC). Additional serum kidney markers, such as creatinine and symmetric dimethylarginine, were compared with USG and UPC to assess their diagnostic value as urinary biomarkers. The results demonstrated proteinuria (UPC > 0.4) or borderline proteinuria (UPC 0.2-0.4) in 49% of the animals. Among these cases, 62% were of renal origin, and 38% were postrenal causes. USG was significantly higher in felids with borderline proteinuria compared to those with proteinuria. A moderate, but significant negative correlation between serum parameters and USG was observed, emphasizing the importance of assessing both diagnostic parameters during kidney evaluations. Additionally, felids with CKD have an increased risk of urinary tract infections, necessitating microscopic urinalysis and bacterial culture analysis. Abnormalities, including hematuria, pyuria, crystalluria, and bacteriuria, were found in approximately 38% of cases through microscopical examination of urine. No complications associated with UGC were observed and abnormal findings were detected in 60% of the cases. Based on these results, the authors recommend the inclusion of UGC and urinalysis as standard diagnostic tools in general health checks for nondomestic felids. This approach provides valuable insights into the early detection and staging of CKD, supporting early intervention and supportive medical care to prolong renal health in these animals.

Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy.

Rosa davurica Pall. is widely used in traditional oriental herbal therapy, but its components and molecular mechanisms of action remain unclear. This study investigates the antidiabetic potential of Rosa davurica Pall. root extract (RDR) and elucidates its underlying molecular mechanisms with in vitro and in vivo models. Data from the current study show that RDR exhibits strong antioxidant activity and glucose homeostasis regulatory effects. It significantly impacts glucose homeostasis in C2C12 skeletal muscle cells by inhibiting α-glucosidase activity. Further molecular mechanistic studies revealed that RDR promoted glucose uptake by phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC), but not Phosphatidylinositol 3-kinase (PI 3-kinase)/Akt in C2C12 skeletal muscle cells. These actions increased the expression and translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. In addition, RDR treatment in the STZ-induced diabetic rats remarkably improved the low body weight, polydipsia, polyphagia, hyperglycemia, and islet architecture and increased the insulin/glucose ratio. The liver (ALT and AST) and kidney marker enzyme (BUN and creatinine) levels were restored by RDR treatment as well. Phytochemical analysis identified eight major constituents in RDR, crucial for its antioxidant and antidiabetic activity. Through the molecular docking of representative glucose transporter GLUT4 with these compounds, it was confirmed that the components of RDR had a significantly high binding score in terms of structural binding. These findings from the current study highlight the antidiabetic effects of RDR. Collectively, our data suggest that RDR might be a potential pharmaceutical natural product for diabetic patients.

Targeting Lactobacillus johnsonii to reverse chronic kidney disease

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

Glutathione Levels and Lipid Oxidative Damage in Selected Organs of Obese Koletsky and Lean Spontaneously Hypertensive Rats.

Koletsky rats, the genetically obese strain of spontaneously hypertensive rats (SHROB), are the well-accepted animal model of human metabolic syndrome. They are characterized by early onset obesity, spontaneous hypertension, hyperinsulinemia, hyperlipidemia, proteinuria and shortened life-span. One of the factors in the pathogenesis of metabolic syndrome is oxidative stress. The aim of the present study was to compare two parameters related to oxidative stress: the levels of the main intracellular antioxidant, reduced glutathione as well as the indirect indicator of lipid peroxidation damage, thiobarbituric acid-reactive substances (TBARS) in heart, renal cortex and medulla and liver in male lean spontaneously hypertensive rats (SHR) and obese Koletsky rats. We did not find any significant differences in these markers in heart and kidneys. However, we found significantly lower glutathione level in Koletsky rat liver compared with SHR (5.03+/-0.23 vs. 5.83+/-0.14 µmol/g tissue, respectively). On the contrary, we observed significantly higher TBARS levels in Koletsky rat liver compared with SHR (28.56+/-2.15 vs. 21.83+/-1.60 nmol/mg protein, respectively). We conclude that the liver is the most sensitive tissue to oxidative damage with the significantly decreased concentration of glutathione and the significantly increased concentration of TBARS in obese Koletsky rats in comparison with lean control SHR.