Serum Blood Urea Nitrogen Research Articles

Impact of diversified grazing systems on milk production, nutrient use and enteric methane emissions in dual-purpose cows.

This study evaluated three continuous grazing systems: Brachiaria Brizantha, Clitoria ternatea and naturalized pastures, complemented with commercial concentrate and C. ternatea silage on milk yield, nutrient use and enteric methane (CH4) emissions. Nine multiparous cows of local Zebu breeds, with an average weight of 448 ± 87kg, were used. The chemical composition of the food was determined. Live weight, milk production, and quality were assessed. Furthermore, serum urea, urea nitrogen, creatinine and glucose in blood were monitored, and nitrogen use efficiency were calculated. Enteric methane (CH4) emissions were estimated using Tier-2 methodology. A 3 × 3 latin square experimental design was applied. The grazing systems of B. brizantha and C. ternatea had the greater live weights of 465.8 and 453.3kg/cow, although the latter is similar to naturalized pasture. Milk production and quality were not affected by grazing system, with the exception of the non-fat solids, where the C. ternatea system was lower (102.2g/kg) than the other grazing systems. The crude protein and N intake, and N excretion in feces and urine were lower in naturalized pasture systems (1139.0g/day). N outputs in milk was high in the C. ternatea system (56.3g/cow/day). The naturalized pastures systems showed the better feed use efficiency (25.7%) compared to others. Serum urea and blood urea nitrogen were greater in B. brizantha followed by C. ternatea. Enteric CH4 emissions were indifferent among grazing systems when expressed as a percentage of greenhouse gases (7.1%). In conclusion, the grazing C. ternatea supplemented with commercial concentrate and C. ternatea silage maintains milk production and quality, reduced cow/day emissions (by 2.5%) and lowered energy losses as methane.

Acute Dapagliflozin Administration Ameliorates Cardiac Surgery-Associated Acute Kidney Injury in a Rabbit Model.

Several studies have shown that sodium-glucose cotransporter-2 inhibitors have a renoprotective effect on acute kidney injury (AKI), but their effect on cardiac surgery-associated AKI is unknown. AKI was induced in 25 rabbits without diabetes mellitus by cardiopulmonary bypass (CPB) for 2 h and they were divided into 5 groups: sham; dapagliflozin-treated sham; CPB; dapagliflozin-treated CPB; and furosemide-treated CPB (n=5 in each group). Dapagliflozin was administered via the femoral vein before initiating CPB. Kidney tissue and urine and blood samples were collected after the surgical procedure. There were no differences in the hemodynamic variables of each group. Dapagliflozin reduced serum creatinine and blood urea nitrogen concentrations, and increased overall urine output (all P<0.05). Hematoxylin and eosin staining showed that the tubular injury score was improved after dapagliflozin administration (P<0.01). Dapagliflozin administration mitigated reactive oxygen species and kidney injury molecule-1 as assessed by immunohistochemistry (both P<0.0001). Protein expression analysis showed improvement of inflammatory cytokines and apoptosis, and antioxidant enzyme expression was elevated (all P<0.05) through activation of the nuclear factor erythroid 2-related factor 2 pathway (P<0.01) by dapagliflozin. Acute intravenous administration of dapagliflozin protects against CPB-induced AKI. Dapagliflozin may have direct renoprotective effects in renal tubular cells.

Renal Artery Coil Embolization as an Endovascular Approach for Establishing a Rabbit Model of Chronic Kidney Disease

PurposeTo investigate the safety and feasibility of renal artery coil embolization for establishing chronic kidney disease (CKD) in rabbits. Materials and MethodsTen male adult New Zealand rabbits underwent renal artery coil embolization. Initially, the main renal artery on 1 side was completely embolized, followed by embolization of approximately two-thirds of the primary branches of the contralateral renal artery 1 week later. Four rabbits were randomly chosen for sacrifice at 4 weeks after embolization, whereas the remaining 6 were sacrificed at 8 weeks after embolization. The assessment encompassed the animals’ general condition, angiography, biochemical parameters, inflammatory markers, and histopathological examination of the kidneys and hearts. ResultsFour weeks after embolization, serum creatinine level showed a substantial increase (2.4 mg/dL [SD ± 0.6]; P = .009 vs baseline), with a subsequent 4.12-fold elevation at 8 weeks after embolization (4.9 mg/dL [SD ± 1.4]; P < .001 vs baseline). Additionally, considerable increases in serum blood urea nitrogen, calcium, and potassium ions were observed at 8 weeks after embolization (58.3 mg/dL [SD ± 19.0]; P < .001 vs baseline; 23.1 mg/dL [SD ± 4.4]; P < .001 vs baseline; and 6.3 mEq/L [SD ± 0.7]; P < .001 vs baseline, respectively). The completely embolized kidney exhibited notable atrophy, severe fibrosis, and cortical calcification, whereas the contralateral partially embolized kidney displayed compensatory hypertrophy, along with glomerulosclerosis, tubular dilation, tubular casts, and interstitial fibrosis. ConclusionsRenal artery coil embolization proved to be effective and safe for establishing a CKD model in rabbits.

Moringa oleifera-based feed supplement protects against renal ischaemia/reperfusion injury via downregulation of Bax/caspase 3 signaling.

Ischaemia/reperfusion (I/R) may lead to acute kidney injury via the induction of oxidative stress. On the other hand, Moringa oleifera has been reported to exert antioxidant activities. This study was designed to assess whether or not Moringa oleifera-based feed supplement could prevent I/R-induced renal injury. Renal I/R was induced by occluding the right renal artery for 30 min followed by a 2-h reperfusion. Renal I/R led to increased absolute renal weight and renal organo-somatic weight index. Renal I/R also caused distortion of renal histoarchitecture and impaired renal function evidenced by elevated serum creatinine and blood urea nitrogen. In addition, renal I/R significantly elevated renal levels of hydrogen peroxide, MDA, and advanced oxidation protein products, but suppressed the levels of reduced glutathione, protein thiol, and non-protein thiol, and the activities of superoxide dismutase and glutathione peroxidase. In addition, renal I/R up-regulated myeloperoxidase activity and the renal levels of NO, TNF-α, and IL-6. Renal I/R also up-regulated Bax and caspase 3 expression in the kidney. Furthermore, I/R-driven structural and biochemical alterations were markedly inhibited by Moringa oleifera-based feed supplement. These results suggest that Moringa oleifera-based feed supplement may preserve the gross and histoarchitectural integrity of the kidney as well as renal function via downregulation of Bax/caspase 3 signaling by targeting oxidative stress, inflammation and apoptosis in the kidney of I/R rat.

Inhibition of Usp14 ameliorates renal ischemia-reperfusion injury by reducing Tfap2a stabilization and facilitating mitophagy

Mitochondrial dysfunction is recognized as a pivotal contributor to the pathogenesis of renal ischemia-reperfusion (IR) injury. Mitophagy, the process responsible for removing damaged protein aggregates, stands as a critical mechanism safeguarding cells against IR injury. Currently, the role of deubiquitination in regulating mitophagy still needs to be completely elucidated. This study aimed to evaluate the impact of ubiquitin-specific peptidase 14 (Usp14), a deubiquitinase, in IR injury by influencing mitophagy. Utilizing a murine model of renal IR injury, Usp14 silencing was found to ameliorate kidney injury, leading to decreased levels of serum creatinine and blood urea nitrogen, alongside diminished oxidative stress and inflammation. In renal epithelial cells subjected to hypoxia/reoxygenation (H/R), Usp14 knockdown increased cell viability and reduced apoptosis. Further mechanistic studies revealed that Usp14 interacted with and deubiquitinated transcription factor AP-2 alpha (Tfap2a), thereby suppressing its downstream target gene, TANK binding kinase 1 (Tbk1), to influence mitophagy. Tfap2a overexpression or Tbk1 inhibition reversed the protective effects of Usp14 silencing on renal tubular cell injury and its facilitation of mitophagy. In summary, our study demonstrated the renoprotective role of Usp14 knockdown in mitigating renal IR injury by promoting Tfap2a-mediated Tbk1 upregulation and mitophagy. These findings advocate for exploring Usp14 inhibition as a promising therapeutic avenue for mitigating IR injury, primarily by enhancing the clearance of damaged mitochondria through augmented mitophagy.

Efficacy of Flexible Ureteroscopy Lithotripsy and Percutaneous Nephrolithotomy in the Treatment of Patients with Kidney Stones and Their Impact on Inflammatory Response and Renal Function.

Kidney stones are one of the most common benign diseases in urology. As technology updates and iterates, more minimally invasive and laparoscopic surgeries with higher safety performance appear. This paper explores the effectiveness of retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) in treating kidney stones, focusing on their effects on inflammatory responses and renal function. We conducted a retrospective analysis of 200 patients with kidney stones treated in our hospital between June 2019 and June 2023. 100 patients who underwent RIRS were included in the RIRS group. Another 100 patients who underwent PCNL treatment were included in the PCNL group. The intraoperative blood loss, operation duration, and hospitalization time of the two groups of patients were recorded and compared. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors in the serum of the two groups of patients: [serum amyloid A (SAA), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRP)] and renal function index [blood urea nitrogen (BUN), creatinine (Scr) and serum cystatin (Cys-c)]. The two groups of patients were recorded separately: Postoperative complications and stone-free rate. Operation duration was longer for the RIRS group than the PCNL group, which exhibited significantly less intraoperative blood loss and shorter hospital stays (p < 0.05). Before surgery, there was no statistically significant difference in the serum levels of SAA, IL-6, and CRP between the two groups of patients (p > 0.05). On the first day after surgery, the serum SAA levels in both groups were lower than before surgery, IL-6 and CRP levels were higher than before surgery, and the serum levels of SAA, IL-6, and CRP in the RIRS group were significantly lower than those in the PCNL group. The difference was statistically significant (p < 0.05). Before surgery, there was no statistically significant difference in the serum BUN, Scr, and Cys-c levels between the two groups of patients (p > 0.05). On the first day after surgery, the serum BUN, Scr, and Cys-c levels of the two groups of patients were significantly higher than those before surgery. The serum BUN, Scr, and Cys-c levels of the RIRS group were significantly lower than those of the PCNL group, and the difference was statistically significant (p < 0.05). Both surgical methods have sound stone-clearing effects regarding long-term stone clearance rates 1 month and 3 months after surgery (p > 0.05). PCNL had a better stone clearance rate on the 2nd postoperative day (p < 0.05). The incidence of postoperative complications in the RIRS group was significantly lower than that in the PCNL group, and the difference was statistically significant (p < 0.05). For kidney stones ≤2 cm, PCNL showed higher stone clearance rates on the second postoperative day. However, RIRS and PCNL demonstrated adequate long-term stone clearance at 1 and 3 months post-surgery. Both surgical methods are safe and effective, and RIRS is safer than PCNL. Compared with PCNL, RIRS is a new method of kidney stone operation, which has less trauma to the patient's body and fewer complications after the operation, speeding up the recovery process of the patient.

Eriocitrin prevents Sepsis-induced acute kidney injury through anti-inflammation and anti-oxidation via modulating Nrf2/DRP1/OPA1 signaling pathway

BackgroundSevere inflammation and oxidative stress are characteristics of sepsis-associated kidney injury with high morbidity and mortality. Eriocitrin (ERI) has shown promise in suppressing sepsis-associated kidney injury and LPS-induced periodontal disease, however, its efficacy in alleviating SAKI remains unexplored. This study aimed to investigate the therapeutic potential of ERI on SAKI through in vivo and in vitro experiments, elucidating its underlying mechanism. MethodsThe therapeutic effects of ERI against SAKI were evaluated by survival rate, changes of serum creatinine (Scr) and blood urea nitrogen (BUN) and statistic of renal histological score in a Cecal ligation and puncture (CLP)-induced septic mice. Impactions about anti-coagulation, anti-inflammation, anti-oxidative stress and improvement of mitochondrial damage and mitochondrial morphology were further assayed. In vitro, HUVECs upon stimulation of LPS with or without different dosage of ERI, followed by evaluating changes in inflammation, mitochondrial dynamic equilibrium and signaling pathways. ResultsERI demonstrated ameliorative effects on SAKI by attenuating inflammation, oxidative stress and coagulation evidenced by the improved survival rate, alleviated kidney histological injury, declined BUN and Scr in serum and diminished levels of inflammation cytokines, and coagulation factors. Mechanistically, ERI suppressed DRP1-regulated mitochondrial fission and promoted OPA1-modulated mitochondrial fusion by activating Nrf2 in septic mice and LPS-stimulated HUVECs, which maintained mitochondrial dynamic equilibrium, improved mitochondrial morphology, assured integrity of mitochondrial function, decreased oxidative stress, impeded overwhelming inflammation, and thus, played a pivotal role in ERI's protection against SAKI. ConclusionOur data confirmed the therapeutic potential of ERI in mitigating SAKI，suggesting its viability as a pharmacological agent in clinic settings.

Impact of iodine contrast media on gamma camera-based GFR and factors affecting the difference between serum creatinine-based estimated GFR and Gate's GFR.

We aimed to elucidate the factors underlying the difference between estimated glomerular filtration rate (eGFR) calculated from serum creatinine and Gate's GFR (gGFR) measured using technetium-99m diethylene triamine pentaacetic acid ( 99m Tc-DTPA) scintigraphy. This study was based on consecutive patients who underwent 99m Tc-DTPA scintigraphy at our hospital between January 2021 and December 2022 and whose blood serum creatinine data were obtained on the same day as the 99m Tc-DTPA scintigraphy. Relationships between the ratio of gGFR and eGFR (gGFR/eGFR) and age, sex, BMI, visceral fat, psoas muscle index (PMI), serum blood urea nitrogen, and creatinine level were investigated based on 75 patients. Additionally, for 44 patients who had two or more follow-up DTPA studies, we compared gGFR values for studies that used iodine contrast media (ICM) for computed tomography before same-day 99m Tc-DTPA studies and those that did not in the same patients. Weak correlations were observed between gGFR/eGFR and PMI ( r = 0.30), BMI ( r = 0.24), and the visceral fat area ( r = 0.33). Multi-regression analyses showed that gGFR/eGFR was correlated with PMI ( β = 0.34, P < 0.01) and approached significance with the visceral fat area ( β = 0.24, P = 0.05). A significant difference was observed in gGFR between patients who received ICM before the 99m Tc-DTPA renogram and those who did not ( P < 0.001, eGFR 80.5 ± 19.0 vs. 91.7 ± 27.8 ml/min). ICM administration temporarily decreased gGFR, and increased muscle mass increased the difference between eGFR and gGFR values.

Pharmacokinetics and Nephrotoxicity of Polymyxin MRX-8 in Rats: A Novel Agent against Resistant Gram-Negative Bacteria.

MRX-8 is a novel polymyxin for carbapenem-resistant Gram-negative infections that has been recently evaluated in Phase I clinical trials. Herein, its pharmacokinetics (PK) and nephrotoxicity in rats are reported for the first time. This study aimed at pre-clinical PK and safety assessments. An LC-MS/MS method was developed to determine concentrations of MRX-8 and its major deacylation metabolite, MRX-8039, in rat plasma. Animals were administered a single dose of MRX-8 (2, 4, 6, and 8 mg/kg) or comparator polymyxin B (PMB) (4 and 8 mg/kg) to compare the kidney injury known for the polymyxin drug class. Nephrotoxicity was evaluated using serum creatinine, blood urea nitrogen (BUN) biomarkers, and renal histopathology. In rats, MRX-8 displayed linear PK within the range of 2-8 mg/kg, with approximately 4% of MRX-8 converted to MRX-8039. MRX-8 induced only mild increases in serum creatinine and BUN levels, with an apparent decrease in nephrotoxicity within 24 h, in contrast to PMB, which exhibited a significant and more persistent toxicity. Additional nephrotoxicity biomarkers (plasma NGAL and urinary NGAL, KIM-1, and TIMP-1) have confirmed attenuated MRX-8 kidney injury. Histopathology has revealed significantly greater cellular/tissue toxicity for PMB as compared to MRX-8 (variances of p = 0.008 and p = 0.048 vs. saline control, respectively). Thus, MRX-8 induces a mild and reversible kidney injury in rats compared to PMB. These data support a continued evaluation of the novel polymyxin in human trials.

In Vivo Antioxidant and Nephroprotective Effects of Ethanolic Extract of Carica papaya Seeds and Its Isolated Flavonoid on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats.

Background The nephrotoxic side effects of gentamicin, a potent aminoglycoside antibiotic, significantly restrict its clinical use. Identifying compounds that can mitigate this nephrotoxicity is of paramount importance. The research examines how the ethanolic extract of Carica papaya seeds (EECPS) and isoliquiritigenin (ISL), a flavonoid separated from them, protect the kidneys and fight free radicals in gentamicin-treated Wistar albino rats. Methodology A total of 48 mature Wistar albino rats were divided into eight groups, with each group consisting of six rats. The experimental setup included a normal control group receiving oral saline as a negative control, and a standard control group administered gentamicin intraperitoneally (IP) at 100 mg/kg body weight for 13 days to induce nephrotoxicity, followed by oral silymarin at 100 mg/kg body weight as a positive control from days 14 to 21. A toxicant control group was exposed to gentamicin IP without subsequent treatment. Two test groups were given 400 mg/kg and 800 mg/kg of EECPS orally after being given gentamicin. Three other test groups were given 20 mg/kg, 40 mg/kg, and 80 mg/kg of ISL orally after being given gentamicin. Serum levels of creatinine, urea, and blood urea nitrogen (BUN) were used to test renal function. Malondialdehyde (MDA),nitric oxide (NO), and reduced glutathione (GSH), which are signs of oxidative stress, were also measured in renal tissues. Results Gentamicin administration markedly increased serum creatinine, urea, and BUN levels, confirming its nephrotoxic effect. Nephroprotection depended on the dose of EECPS and ISL used. It was found that 80 mg/kg of ISL had the most powerful effect, which was not what was thought at first. These treatments effectively reduced MDA and NO levels while enhancing GSH levels, exhibiting their strong antioxidant properties. Notably, the nephroprotective efficacy of these treatments exceeded that of silymarin, a known nephroprotective agent. Histopathological analysis confirmed reduced renal damage and enhanced tissue repair in the treated groups. Conclusions These findings demonstrate how effective EECPS and ISL are at shielding the kidneys from gentamicin-caused damage. They do this by acting as antioxidants and nephroprotectants. Their ability to protect kidney function and fight oxidative stress makes them interesting as possible treatments for gentamicin-related kidney damage. These results advocate for further investigation into the utility of these natural compounds in the management of nephrotoxicity.

LC-MS/MS metabolomics approach for chemical characterization of Beta vulgaris subspecies maritima extract through untargeted molecular networking, in correlation to its renoprotective activity in renal ischemia/reperfusion induced injury model in rats

This study evaluates the reno-protective effect of Beta vulgaris subspecies maritima lyophilized 70% ethanolic extract (BVLE) in renal ischemia/reperfusion (I/R) induced injury model in rats. Detailed investigation of the effects of its oral administration was checked. serum blood urea nitrogen (BUN), which was reduced to 0.7 ± 0.04 mmol/L at a dose of 200 mg/Kg of BVLE compared to 1.9 ± 0.08 mmol/L for the I/R group. And creatinine levels were reduced to 1.2 ± 0.06 nmol/L at a dose of 200 mg/Kg of BVLE compared to 4.7 ± 0.12 nmol/L for the I/R group. Oxidative stress biomarkers including MDA (reduced to 0.4 ± 0.03 compared to 1.7 ± 0.05 nmol/mg protein of I/R a dose of 200 mg/Kg) and GSH levels (increased to 1.3 ± 0.03 compared to 0.3 ± 0.02 nmol/mg protein of I/R a dose of 200 mg/Kg). Meanwhile, inflammatory mediators including TNF-α and IL-6 levels were lowered to 46.7 ± 0.60 and 32.1 ± 1.78 pg/mg protein, respectively. Oxidative stress genetic pathways including Nrf2/HO-1 signaling pathway via testing Nrf2 and its dependent HO-1 mRNA expression levels were studied as well. Metabolomic profiling of BVLE was achieved by UPLC-HR-ESIMS coupled with molecular networking. BVLE significantly improved renal inflammatory markers, oxidative stress biomarkers and renal functions test, in dose dependent manner. Thirty-nine compounds were tentatively identified in BVLE by UPLC-MS/MS. Mainly flavonoid glycosides, triterpenoidal saponins and fatty acids. Among identified saponins five unreported betavulgaroside derivatives were tentatively described for the first time.

Dietary supplementation with ellagic acid improves the growth performance, meat quality, and metabolomics profile of yellow-feathered broiler chickens

The aim of this research was to explore the effects of ellagic acid (EA) on growth performance, meat quality, and metabolomics profile of broiler chickens. 240 healthy yellow-feathered broilers were randomly divided into 4 groups (6 replicates/group and 10 broilers /replicate): 1) a standard diet (CON); 2) CON+0.01% EA; 3) CON+0.02% EA; 4) CON+0.04% EA. Compared with the CON group, dietary 0.02% EA increased linearly and quadratically the ADG and lowered F/G ratio from 29 to 56 d and from 1 to 56 d of age (P < 0.05). The EA groups had higher spleen index and showed linear and quadratic improve thymus index (P < 0.05). A total of 0.02% EA linearly and quadratically increased the leg muscle percentage and quadratically increased the breast muscle percentage (P < 0.05). Compared to the control diet, 0.02% EA decreased quadratically the L* and increased a* of breast muscle at 45 min postslaughter (P < 0.05), and quadratically decreased (P < 0.05) the b* and increased linearly and quadratically (P < 0.05) drip loss. Additionally, EA improved linearly and quadratically (P < 0.05) serum total protein concentration and reduced linearly and quadratically (P < 0.05) serum blood urea nitrogen concentration. A total of 0.02% EA quadratically increased catalase activity and decreased malondialdehyde concentration in breast muscle compared with the control diet (P < 0.05). 0.02% and 0.04% EA could linearly and quadratically increase (P < 0.05) the concentrations of histidine, leucine and essential amino acids (EAA), 0.02% EA could linearly and quadratically increase (P < 0.05) the concentrations of threonine, glutamate, and flavored amino acids in breast muscle. 0.02% EA linearly and quadratically improved the C20:3n6, C22:6n3, polyunsaturated fatty acid (PUFA) concentrations, and the ratio of PUFA to saturated fatty acids (SFA), but reduced the C16:0 and the SFA concentrations in breast muscle than the CON group (P < 0.05). The EA diet linearly increased (P = 0.035) and quadratically tended (P = 0.068) to regulate the C18:2n6c concentration of breast muscle. Metabolomics showed that alanine metabolism, aspartate and glutamate metabolism, arginine and proline metabolism, taurine and hypotaurine metabolism, and glycerophospholipid metabolism were the most differentially abundant. These results showed that EA supported moderate positive effects on growth performance, meat quality, and metabolomics profile of broilers.

Effect of High Altitude on Serum Biochemical Parameters, Immunoglobulins, and Rumen Metabolism of Sanhe Heifers

Rumen metabolism is closely related to feed utilization and the environmental adaptability of cows. However, information on the influence of altitude on ruminal metabolism is limited. Our study aimed to investigate differences in rumen metabolism and blood biochemical indicators among Sanhe heifers residing at various altitudes. A total of 20 serum and ruminal fluid samples were collected from Sanhe heifers in China, including those from Hulunbeier City (approximately 700 m altitude; 119°57′ E, 47°17′ N; named LA) and Lhasa City (approximately 3650 m altitude; 91°06′ E, 29°36′ N; named HA). Compared with LA heifers, HA heifers had higher levels of serum cortisol, glucose, and blood urea nitrogen (p &lt; 0.05) and lower Ca2+ concentrations (p &lt; 0.05). Using liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomic technology, we identified a significant difference in 312 metabolites between the LA and HA groups. Metabolic pathway analysis, based on significantly different rumen metabolites, identified 20 enriched metabolic pathways within hierarchy III, which are encompassed within 6 broader metabolic pathways in hierarchy I. This study constitutes the first elucidation of the altitudinal adaptation mechanism of ruminants from the perspective of rumen metabolism, thereby offering a novel angle for investigating high-altitude adaptation in both humans and animals.

Functional MRI assessment of microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction

To explore the value of functional magnetic resonance imaging (MRI) techniques, including intravoxel incoherent motion (IVIM), T1 mapping, and T2 mapping, in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction (IUGR). An IUGR rat model was established through a low-protein diet during pregnancy. Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group, while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group (n=8 for each group). The apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (D*), perfusion fraction (f), T1 value, and T2 value of the renal cortex and medulla were compared, along with serum creatinine and blood urea nitrogen levels among the groups. The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group, and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group (P<0.05). The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group, and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group, with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group (P<0.05). The T2 values in the renal medulla were higher than those in the cortex across all groups (P<0.05). There were no significant differences in the T2 values of either the cortex or medulla among the groups (P>0.05). There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups (P>0.05). Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group, whereas glomerular atrophy, cystic stenosis, and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group. IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats. MRI T1 mapping can be used to evaluate kidney damage in IUGR rats, and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.

Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis.

Tubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti-inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model-induced renal inflammation and fibrosis. In vitro, erastin-induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin-NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4-mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague–Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Beclin-1-Derived Peptide MP1 Attenuates Renal Fibrosis by Inhibiting the Wnt/β-Catenin Pathway.

Renal fibrosis is distinguished by the abnormal deposition of extracellular matrix and progressive loss of nephron function, with a lack of effective treatment options in clinical practice. In this study, we discovered that the Beclin-1-derived peptide MP1 significantly inhibits the abnormal expression of fibrosis and epithelial-mesenchymal transition-related markers, including α-smooth muscle actin, fibronectin, collagen I, matrix metallopeptidase 2, Snail1, and vimentin both in vitro and in vivo. H&E staining was employed to evaluate renal function, while serum creatinine (Scr) and blood urea nitrogen (BUN) were used as main indices to assess pathologic changes in the obstructed kidney. The results demonstrated that daily treatment with MP1 during the 14-day experiment significantly alleviated renal dysfunction and changes in Scr and BUN in mice with unilateral ureteral obstruction. Mechanistic research revealed that MP1 was found to have a significant inhibitory effect on the expression of crucial components involved in both the Wnt/β-catenin and transforming growth factor (TGF)-β/Smad pathways, including β-catenin, C-Myc, cyclin D1, TGF-β1, and p-Smad/Smad. However, MP1 exhibited no significant impact on either the LC3II/LC3I ratio or P62 levels. These findings indicate that MP1 improves renal physiologic function and mitigates the fibrosis progression by inhibiting the Wnt/β-catenin pathway. Our study suggests that MP1 represents a promising and novel candidate drug precursor for the treatment of renal fibrosis. SIGNIFICANCE STATEMENT: This study indicated that the Beclin-1-derived peptide MP1 effectively mitigated renal fibrosis induced by unilateral ureteral obstruction through inhibiting the Wnt/β-catenin pathway and transforming growth factor-β/Smad pathway, thereby improving renal physiological function. Importantly, unlike other Beclin-1-derived peptides, MP1 exhibited no significant impact on autophagy in normal cells. MP1 represents a promising and novel candidate drug precursor for the treatment of renal fibrosis focusing on Beclin-1 derivatives and Wnt/β-catenin pathway.

Modulation of Stem Cell Factor by Forskolin Inhibits the Progression of Tubule Interstitial Fibrosis

Purpose Forskolin is primarily found in the roots of the Coleus forskohlii plant, historically employed in Southeast Asian and Indian Ayurvedic medicine. Mast cells play a crucial role in fibrosis progression, yet their activation and inhibition in animal models are understudied; thus, we explored forskolin’s impact on kidney fibrosis. Materials and Methods Forskolin was evaluated in a mouse model for stem cell factor-induced histamine release, and plasma histamine levels were measured using the enzyme-linked immunosorbent assay. Kidney fibrosis was developed by unilateral ureteral obstruction (UUO). Renal function was assessed by spectrophotometric measurements of serum blood urea nitrogen (BUN) and creatinine. The gene expression of collagen, transforming growth factor-beta (TGF-β), α-smooth muscle actin (α-SMA), interleukin-1 beta (IL-1β), and mast cell protease-5 (MCPT-5) in the kidney was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Histopathological changes in the renal tissues were examined by hematoxylin and eosin (H&amp;E) and Masson’s trichome stain. Results Our results showed that 3 mg/kg forskolin inhibited SCF-induced plasma histamine release in a mouse model. In the 7-day UUO model, forskolin significantly showed inhibition of serum creatinine and blood urea nitrogen compared with the disease group. Forskolin significantly inhibited elevated expression of collagen, TGF-β, α-SMA, IL-1β, and MCPT-5 in the kidneys. Histopathological observation of H&amp;E and Masson trichome-stained kidney forskolin demonstrated a reduction in inflammatory cells, pelvic and tubular dilation, and fibrosis. Conclusion Forskolin showed an anti-fibrotic effect in UUO-induced renal fibrotic mice. Most significantly, forskolin administration showed a decrease in the expression of the mast cell protease MCPT5 in the kidneys. These results imply that forskolin, through modifying SCF activity, may be a viable potential treatment for the attenuation of tubule-interstitial fibrosis.

Allium ureteral stent for refractory ureteral stricture: A single-center study

Purpose: This study aims to investigate the efficacy and safety of Allium metallic ureteral stents in treating patients with refractory ureteral strictures. Materials and methods: A total of 13 patients with refractory ureteral strictures were prospectively enrolled in the study. After ureteral balloon dilation, an Allium stent was inserted into the ureter through the stricture. Serum blood urea nitrogen and creatinine levels, kidney-ureter-bladder x-ray, and renal ultrasonography reports were evaluated preoperatively, 3 months after the procedure, and at the last outpatient visit. Treatment success was defined as improvement in both renal function and the grade of hydronephrosis. Improvement was defined as the enhancement of renal function without the resolution of hydronephrosis. Adverse events were recorded. Results: The median (interquartile range [IQR]) age of the patients was 63 (46–76) years. The median (IQR) follow-up was 15 (13.5–21) months. Treatment success and improvement were noted in 9 (69.2%) and 3 (23.1%) patients, respectively. Compared with the preoperative levels, the median (IQR) serum creatinine levels were significantly improved at 3 months after the operation (1.6 [1.25–2.85] versus 1.2 [1.05–2.05]; P = 0.02) and at the last visit (1.6 [1.25–2.85] versus 1.2 [1.05–1.8]; P = 0.02). Stent migration and encrustation were noted in 3 (23.1%) and 1 (7.7%) patients, respectively. Conclusion: Allium ureteral stents are safe and effective for patients with refractory ureteral strictures.

An Objective Computer-Assisted Measurement of Sonographic Renal Cortical Echogenicity: The Splenorenal Index.

Renal cortical echogenicity represents a marker of renal function. However, evaluation of the renal echotexture is subjective and thus disposed to error and interrater variability. Computer-aided image analysis may be used to objectively assess renal cortical echogenicity by comparing the echogenicity of the left kidney to that of the spleen; the resultant ratio is referred to as the splenorenal index (SRI). We performed a retrospective review of all adult patients who received a renal ultrasound over a 45-day period at our institution. Demographic data and kidney function laboratory values were documented for each patient. Regions of interest (ROIs) were selected in the left renal cortex and spleen using ImageJ software. The SRI was calculated as a ratio of the mean pixel brightness of the left kidney cortex ROI to the mean pixel brightness of the spleen ROI. The SRI was then correlated with serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate. We found that among the 94 patients included in the study, the SRI had a significant positive correlation with serum creatinine ( r = 0.43, P < 0.001) and serum blood urea nitrogen ( r = 0.45, P < 0.001) and negative correlation with estimated glomerular filtration rate ( r = -0.47, P < 0.001). Our data indicate that SRI may serve as a valuable tool for sonographic evaluation of renal parenchymal disease.