Improved Kidney Function Research Articles

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries

Ethnopharmacological relevanceScrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. Aim of the studyThis study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. Materials and methodsBased on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. ResultsA total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as immune cells in the liver. ConclusionXS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients (the SPIREN trial): A Randomized Placebo-Controlled Clinical Trial.

Long-term kidney allograft survival is hampered by progressive interstitial fibrosis and tubular atrophy. The SPIREN trial tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone stabilizes kidney function and attenuates glomerular barrier injury in kidney transplant patients treated with calcineurin inhibitors. Randomized, placebo-controlled, double blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for three years. Glomerular filtration rate was measured along with proteinuria and kidney fibrosis. The primary endpoint was change in measured glomerular filtration rate. Secondary outcomes were 24h proteinuria, kidney allograft fibrosis and cardiovascular events. Measured glomerular filtration rates, 24h proteinuria and blood pressure were determined yearly. Kidney biopsies were collected at baseline and after two years (n=48). Fibrosis was evaluated by quantitative stereology and classified according to Banff. The groups were comparable at baseline except for slightly older allografts in the spironolactone group. Spironolactone reduced measured glomerular filtration rates (up to -7.6 (95% CI -10.9;-4.3) ml/min compared to placebo) independently of time since transplantation and blood pressure with no impact on the kidney function curve over time and reduced 24h proteinuria after one year. There was no significant effect of spironolactone on the development of interstitial fibrosis. Spironolactone added to standard therapy for three years in kidney transplant patients did not improve kidney function, long-term proteinuria or interstitial fibrosis.

Nephroprotective and Anti-Diabetic Potential of Beta vulgaris L. Root (Beetroot) Methanolic Extract in a Rat Model of Type 2 Diabetes Mellitus.

Background and Objectives: Diabetes mellitus is a chronic metabolic disease associated with several complications, including that of kidney disease. Plant-based dietary products have shown promise in mitigating these effects to improve kidney function and prevent tissue damage. This study assessed the possible favorable effects of beetroot extract (BE) in improving kidney function and preventing tissue damage in diabetic rats. Materials and Methods: Type 2 diabetes mellitus (T2DM) was induced using a low dose of streptozotocin (STZ). Both control and rats with pre-established T2DM were divided into six groups (each consisting of eight rats). All treatments were given by gavage and continued for 12 weeks. Fasting blood glucose levels, serum fasting insulin levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum triglycerides, cholesterol, low-density lipoprotein-cholesterol, serum and urinary albumin, and creatinine and urea levels were measured. Apart from this, glutathione, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, and interleukine-6 in the kidney homogenates of all groups of rats were measured, and the histopathological evaluation of the kidney was also performed. Results: It was observed that treatment with BE increased body weight significantly (p ≤ 0.05) to be similar to that of control groups. Fasting glucose, insulin, HOMA-IR levels, and lipid profile in the plasma of the pre-established T2DM rats groups decreased to p ≤ 0.05 in the BE-treated rats as the BE concentration increased. Treatment with BE also improved the renal levels of oxidative stress and inflammatory markers, urinary albumin, and serum creatinine and urea levels. Unlike all other groups, only the kidney tissues of the T2DM + BE (500 mg/kg) rats group showed normal kidney tissue structure, which appears to be similar to those found in the kidney tissues of the control rats groups. Conclusion: we found that streptozotocin administration disturbed markers of kidney dysfunction. However, Beta vulgaris L. root extract reversed these changes through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Vildagliptin Nephroprotective Effect in Rats Model with Cisplatin-Induced Nephrotoxicity

Objective: To evaluate the nephroprotective effect of vildagliptin against cisplatin-induced nephrotoxicity in rats.
 Methods and Materials: Twenty-eight male rats have been divided into four groups: Control (received distal water), cisplatin treated group (received single dose of cisplatin (7mg/kg) intraperitoneally (IP) on day eight), vildagliptin plus cisplatin treated group (received vildagliptin 10mg/kg/day orally for 14 days, seven days before and seven days after the dose of cisplatin on day eight), and vildagliptin treated group (received the same dose and duration of vildagliptin mentioned previously). At the end, blood samples were collected to evaluate tumor necrotic factor-α (TNF-α), caspase-3, total antioxidant capacity (TAOC), urea, and creatinine. The serum levels of these biomarkers were expressed as mean ± standard error of mean. Additionally, kidneys were fixed in formalin for histopathological examination.
 Result: Vildagliptin treatment significantly reduced the serum levels of TNF-α, caspase-3, urea, and creatinine as well as increased the TAOC level in rats treated with vildagliptin plus cisplatin when compared with cisplatin treated group. Histopathological examination further supported the nephroprotective effect of vildagliptin in rats with cisplatin induced nephrotoxicity. 
 Conclusion: Vildagliptin improved kidney function and reduced cisplatin nephrotoxicity which may highlight the nephroprotective effect of this DPP-4 inhibitor against cisplatin-induced nephrotoxicity.

Inhibiting centrosome clustering reduces cystogenesis and improves kidney function in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder accounting for approximately 5% of patients with renal failure, yet therapeutics for the treatment of ADPKD remain limited. ADPKD tissues display abnormalities in the biogenesis of the centrosome, a defect that can cause genome instability, aberrant ciliary signaling, and secretion of pro-inflammatory factors. Cystic cells form excess centrosomes via a process termed centrosome amplification (CA), which causes abnormal multipolar spindle configurations, mitotic catastrophe, and reduced cell viability. However, cells with CA can suppress multipolarity via "centrosome clustering," a key mechanism by which cells circumvent apoptosis. Here, we demonstrate that inhibiting centrosome clustering can counteract the proliferation of renal cystic cells with high incidences of CA. Using ADPKD human cells and mouse models, we show that preventing centrosome clustering with 2 inhibitors, CCB02 and PJ34, blocks cyst initiation and growth in vitro and in vivo. Inhibiting centrosome clustering activates a p53-mediated surveillance mechanism leading to apoptosis, reduced cyst expansion, decreased interstitial fibrosis, and improved kidney function. Transcriptional analysis of kidneys from treated mice identified pro-inflammatory signaling pathways implicated in CA-mediated cystogenesis and fibrosis. Our results demonstrate that centrosome clustering is a cyst-selective target for the improvement of renal morphology and function in ADPKD.

Rescue From Permanent Kidney Injury in Acute Thrombosis of Both Renal Veins, the Inferior Vena Cava, and Both Iliofemoral Veins by Catheter-Based Thrombectomy.

A 33-year-old man with previously diagnosed lupus membranous nephropathy presented with painful swelling in both legs. Laboratory tests revealed acute kidney injury, and imaging studies by duplex ultrasound and computed tomography scan showed acute thrombosis of both renal veins, the infrahepatic inferior vena cava, and both iliofemoral venous segments. Initially, pharmacomechanical thrombolysis led to an insufficient morphological result. The therapeutic breakthrough was achieved by catheter-based mechanical thrombectomy of the infrarenal vena cava and both renal veins, which successfully cleared all affected venous segments from thrombus, paralleled by improvement of the patient's condition. However, after 1 week, the patient experienced recurrent thrombosis of the right renal vein with hemorrhagic infarction of the right kidney. After further optimization of immunomodulatory and antithrombotic therapy, a repeated catheter-based mechanical thrombectomy resulted in sustained clinical improvement and preservation of renal venous drainage and kidney function. Extensive acute thrombosis of both renal veins, the inferior vena cava, and both iliofemoral venous segments is a rare emergency potentially threatening kidney function. Immediate effective thrombus removal is essential to preserve kidney function and can be achieved by catheter-based mechanical thrombectomy embedded in a comprehensive immunomodulatory and antithrombotic therapeutic concept. This case demonstrated the efficacy of a catheter-based therapeutic approach in patients with extensive thrombosis of the venous system. A catheter-based approach must be embedded in a comprehensive medical therapeutic concept, which is essential to achieve a sustainable result.

Analysis of the Therapeutic Efficacy of Laparoscopic Treatment for Fibroepithelial Polyps of the Ureter in Children.

Objective: The aim of this study is to assess the efficacy and safety of laparoscopic surgery in the treatment of pediatric ureteral fibroepithelial polyp (FEP) patients. Our hypothesis is that laparoscopic surgery can effectively treat FEPs while minimizing patient discomfort and complications. Our research aims to evaluate the clinical outcomes of the surgery, including postoperative symptom relief, improvement in kidney function, and risk of postoperative complications. Methods: The clinical records of 34 patients who underwent ureteral polyp surgery at the Department of Urology at Anhui Provincial Children's Hospital between May 2014 and February 2023 were retrospectively analyzed. All patients underwent laparoscopic surgery. Among the 34 pediatric patients, there were 31 males and 3 females, with 2 on the right side and 32 on the left side. Of these cases, 24 polyps were located at the ureteropelvic junction, while seven were found in the upper segment of the ureter and three in its middle segment. Patients' ages ranged from 4 years and 3 months to 15 years, with a median age of 8 years and 6 months. All children presented with varying degrees of hydronephrosis, and preoperative clinical symptoms included ipsilateral flank or abdominal pain, hematuria, and other discomfort. Preoperative examinations mainly comprised ultrasound, intravenous pyelography, CT, or magnetic resonance urography imaging studies, as well as diuretic renography. All pediatric patients underwent laparoscopic excision of the polyp segment of the ureter, followed by renal pelvis ureteroplasty or ureter-to-ureter anastomosis. Results: All patients underwent surgery without conversion to open surgery. The surgical duration ranged from 72 to 313 minutes, with an average of 179.5 minutes. The average intraoperative blood loss was 14 mL. Postoperatively, one patient experienced leakage at the anastomotic site; however, no other significant complications occurred during or after the procedure. Postoperative histopathology confirmed the presence of FEPs in the ureter for all cases. All patients experienced a favorable postoperative recovery, with hospitalization periods ranging from 3 to 16 days and an average stay of 8.6 days. A Double-J stent was inserted in all patients for a duration of 1 to 2 months after surgery, and upon removal, follow-up color Doppler ultrasound revealed reduced hydronephrosis within 1 to 3 months. Follow-up examinations were conducted at intervals ranging from 3 to 108 months postsurgery, with an average follow-up time of 42.2 months, during which no recurrence of ureteral polyps or symptoms such as pain and hematuria was observed. Conclusions: The findings of this study demonstrate that laparoscopic excision of the polyp segment of the ureter, renal pelvis ureteroplasty, and ureter-to-ureter anastomosis represent safe and effective treatment modalities for pediatric FEPs in the ureters. This technique offers several advantages, including minimal invasiveness, rapid recovery, and definitive therapeutic efficacy, which effectively alleviate clinical symptoms and improve hydronephrosis.

Motion-compensated image reconstruction for improved kidney function assessment using dynamic contrast-enhanced MRI.

Accurately measuring renal function is crucial for pediatric patients with kidney conditions. Traditional methods have limitations, but dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a safe and efficient approach for detailed anatomical evaluation and renal function assessment. However, motion artifacts during DCE-MRI can degrade image quality and introduce misalignments, leading to unreliable results. This study introduces a motion-compensated reconstruction technique for DCE-MRI data acquired using golden-angle radial sampling. Our proposed method achieves three key objectives: (1) identifying and removing corrupted data (outliers) using a Gaussian process model fitting with a -space center navigator, (2) efficiently clustering the data into motion phases and performing interphase registration, and (3) utilizing a novel formulation of motion-compensated radial reconstruction. We applied the proposed motion correction (MoCo) method to DCE-MRI data affected by varying degrees of motion, including both respiratory and bulk motion. We compared the outcomes with those obtained from the conventional radial reconstruction. Our evaluation encompassed assessing the quality of images, concentration curves, and tracer kinetic model fitting, and estimating renal function. The proposed MoCo reconstruction improved the temporal signal-to-noise ratio for all subjects, with a 21.8% increase on average, while total variation values of the aorta, right, and left kidney concentration were improved for each subject, with 32.5%, 41.3%, and 42.9% increases on average, respectively. Furthermore, evaluation of tracer kinetic model fitting indicated that the median standard deviation of the estimated filtration rate ( ), mean normalized root-mean-squared error (nRMSE), and chi-square goodness-of-fit of tracer kinetic model fit were decreased from 0.10 to 0.04, 0.27 to 0.24, and, 0.43 to 0.27, respectively. The proposed MoCo technique enabled more reliable renal function assessment and improved image quality for detailed anatomical evaluation in the case of bulk and respiratory motion during the acquisition of DCE-MRI.

Cerium-Luteolin Nanocomplexes in Managing Inflammation-Related Diseases by Antioxidant and Immunoregulation.

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a pivotal role in inflammation-related diseases. Excessive ROS levels can induce cellular damage and impair normal physiological functions, triggering the release of inflammatory mediators and exacerbating the inflammatory response, ultimately leading to irreversible tissue damage. In this study, we synthesized cerium ion-luteolin nanocomplexes (CeLutNCs) by coordinating Ce ions with the natural product luteolin, aiming to develop a therapeutic agent with excellent antioxidant and immunoregulation properties for ROS-related inflammation treatment. In vitro experiments demonstrated that the prepared CeLutNCs effectively scavenged excess ROS, prevented cell apoptosis, down-regulated levels of important inflammatory cytokines, regulated the response of inflammatory macrophages, and suppressed the activation of the nuclear factor-κ-gene binding (NF-κB) pathway. In an acute kidney injury (AKI) animal model, CeLutNCs exhibited significant efficacy in improving kidney function, repairing damaged renal tissue, and reducing oxidative stress, inflammatory response, and cellular apoptosis. Moreover, the therapeutic potential of CeLutNCs in an acute lung injury (ALI) model was confirmed through the assessment of inflammatory responses and histopathological studies. This study emphasizes the effectiveness of these metal-natural product coordination nanocomplexes as a promising therapeutic approach for preventing AKI and other diseases associated with oxidative stress.

SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.

Sodium glucose co-transporter-2 (SGLT2) inhibitors stimulate renal excretion of sodium and glucose and exert renal protective effects in patients with (non-)diabetic chronic kidney disease (CKD) and may as well protect against acute kidney injury (AKI). The mechanism behind this kidney protective effect remains unclear. Juxtaglomerular cells of renin lineage (CoRL) have been demonstrated to function as progenitors for multiple adult glomerular cell types in kidney disease. This study assesses the impact of SGLT2 inhibition on the repopulation of glomerular cells by CoRL and examines their phenotypic commitment. Experiments were performed in Ren1cre-tdTomato lineage-trace mice. Either 5/6 nephrectomy (5/6NX) modeling CKD or bilateral ischaemia reperfusion injury (bIRI) mimicking AKI was applied, while the SGLT2 inhibitor empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days. Both 5/6NX and bIRI-induced kidney injury increased the number of glomerular CoRL-derived cells. SGLT2 inhibition improved kidney function after 5/6NX, indicated by decreased blood creatinine and urea levels, but not after bIRI. In line with this, empagliflozin in 5/6NX animals resulted in less glomerulosclerosis, while it did not affect histopathological features in bIRI. Treatment with empagliflozin resulted in an increase in the number of CoRL-derived glomerular cells in both 5/6NX and bIRI conditions. Interestingly, SGLT2 inhibition led to more CoRL-derived podocytes in 5/6NX animals, whereas empagliflozin-treated bIRI mice presented with increased levels of parietal epithelial and mesangial cells derived from CoRL. We conclude that SGLT2 inhibition by empagliflozin promotes CoRL-mediated glomerular repopulation with selective CoRL-derived cell types depending on the type of experimental kidney injury. These findings suggest a previously unidentified mechanism that could contribute to the renoprotective effect of SGLT2 inhibitors.

Effect of Blend of Metanil Yellow and Tartrazine on Different Organs of Albino Rat

Background: Tartrazine and metanil yellow are organic azo dyes widely used in food products, drugs, and cosmetics. The present study was conducted to evaluate the toxic effect of these food colors on the liver, and kidneys of albino rats. The study also evaluates the protective effect of quercetin as an antioxidant against the toxic effect of these food colors. Methods: Eighty adult albino rats were divided into 8 groups. Control group, 3 groups were treated with a blend of tartrazine and metanil yellow in 3 doses of 25, 50, and 75 mg/kg for 30 days by gavage, one positive control group was treated with quercetin 50 mg/kg for 30 days, and three groups were treated with the blend of tartrazine and metanil yellow plus 50 mg/kg of quercetin. At the end of the experiment, serum samples were collected to evaluate liver and kidney functions. Liver, kidney samples were fixed in 10% formalin and routinely prepared for paraffin sectioning and staining for histopathological examination. Results: The study showed a significant elevation of liver and kidney function after treatment with the food color blend. Also, a significant improvement in liver and kidney function was observed after treatment with quercetin. Histopathological examination showed mild to moderate changes in the liver and kidney which improved after quercetin treatment. Conclusion: The current sub-chronic study concluded that a blend of tartrazine and metanil yellow caused significant biochemical and histological changes in different organs of albino rats. Therefore, prolonged consumption of these substances leads to adverse effects on human health. Also, quercetin is vital in protecting the body against the toxic effects of food color blends.

Combination of allopurinol with Dahuang Mudan Tang significantly improve kidney function and alleviate oxidative stress and inflammation of chronic kidney disease stage Ⅰ-Ⅲ patients with hyperuricemia.

To evaluate the effect of Dahuang Mudan Tang (, DHMD) and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinical management of chronic kidney disease complications. A total of 80 chronic kidney patients staged G1-G3b with hyperuricemia were randomly grouped to receive single allopurinol treatment (control) and combined treatment with DHMD (treated) for 8 weeks. The kidney function and proteinuria indicators of patients were compared between pre-and post-treatment. The oxidative stress and inflammation responses were evaluated by corresponding indicators and cytokines. The clinical efficiency rate and adverse reaction events were also summarized to assess the therapeutic efficiency and safety. The kidney function and proteinuria of enrolled patients were alleviated after their therapies, behaved as the increasing estimated glomerular filtration rate and decreasing serum creatinine, serum uric acid, urea nitrogen, 24 h urine protein levels. On the other hand, the malondialdehyde level and pro-inflammation cytokines were suppressed by the therapies, and the superoxide dismutase was found to be significantly enhanced. Patients in the treated groups showed a better recovery in kidney function, proteinuria, oxidative stress, and inflammation response. Moreover, patients in the treated group showed a higher efficiency rate (95%) and fewer adverse reaction events (5%). The combination of allopurinol with DHMD significantly promoted the recovery of chronic kidney disease stage G1-G3b patients with hyperuricemia, which can be considered a novel clinical therapeutic strategy.

Automated Electronic Alert for the Care and Outcomes of Adults With Acute Kidney Injury

Despite the expansion of published electronic alerts for acute kidney injury (AKI), there are still concerns regarding their effect on the clinical outcomes of patients. To evaluate the effect of the AKI alert combined with a care bundle on the care and clinical outcomes of patients with hospital-acquired AKI. This single-center, double-blind, parallel-group randomized clinical trial was conducted in a tertiary teaching hospital in Nanjing, China, from August 1, 2019, to December 31, 2021. The inclusion criteria were inpatient adults aged 18 years or older with AKI, which was defined using the Kidney Disease: Improving Global Outcomes creatinine criteria. Participants were randomized 1:1 to either the alert group or the usual care group, which were stratified by medical vs surgical ward and by intensive care unit (ICU) vs non-ICU setting. Analyses were conducted on the modified intention-to-treat population. A programmatic AKI alert system generated randomization automatically and sent messages to the mobile telephones of clinicians (alert group) or did not send messages (usual care group). A care bundle accompanied the AKI alert and consisted of general, nonindividualized, and nonmandatory AKI management measures. The primary outcome was maximum change in estimated glomerular filtration rate (eGFR) within 7 days after randomization. Secondary patient-centered outcomes included death, dialysis, AKI progression, and AKI recovery. Care-centered outcomes included diagnostic and therapeutic interventions for AKI. A total of 2208 patients (median [IQR] age, 65 [54-72] years; 1560 males [70.7%]) were randomized to the alert group (n = 1123) or the usual care group (n = 1085) and analyzed. Within 7 days of randomization, median (IQR) maximum absolute changes in eGFR were 3.7 (-6.4 to 19.3) mL/min/1.73 m2 in the alert group and 2.9 (-9.2 to 16.9) mL/min/1.73 m2 in the usual care group (P = .24). This result was robust in all subgroups in an exploratory analysis. For care-centered outcomes, patients in the alert group had more intravenous fluids (927 [82.6%] vs 670 [61.8%]; P < .001), less exposure to nonsteroidal anti-inflammatory drugs (56 [5.0%] vs 119 [11.0%]; P < .001), and more AKI documentation at discharge (560 [49.9%] vs 296 [27.3%]; P < .001) than patients in the usual care group. No differences were observed in patient-centered secondary outcomes between the 2 groups. Results of this randomized clinical trial showed that the electronic AKI alert did not improve kidney function or other patient-centered outcomes but changed patient care behaviors. The findings warrant the use of a combination of high-quality interventions and AKI alert in future clinical practice. ClinicalTrials.gov Identifier: NCT03736304.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Features of Klotho Protein Expression in Rat Kidneys in Experimental Hyperglycemia Against the Background of Pharmacological Correction with GABA Derivatives

The aim is to identify the features of Klotho protein expression in the epithelium of the convoluted tubules of the kidney during prolonged experimental hyperglycemia and pharmacological correction with GABA derivatives. Material and methods. The study used 50 mongrel male rats (initial weight: 330,0–360,0 g) with streptozotocin diabetes lasting 6 months. 6 months after the injection of streptozotocin (60 mg/kg), animals with a glycemic level of ≥ 15 mmol/l were included in the study (after 4 hours of food deprivation), then GABA derivatives (aminalon, mefargine, succicard) were administered orally for 30 days. Proteinuria and serum creatinine concentrations were evaluated. After euthanasia, kidney tissue was fixed in buffered neutral formalin and examined using immunofluorescence microscopy. The intensity of the glow was evaluated based on a visual-analog scale. Results. In the group with chronic hyperglycemia without treatment, there was a significant increase in the protein content in daily urine and serum creatinine levels (p&lt;0,05). In the group of animals with chronic hyperglycemia without treatment, there was a significant decrease in the expression of Klotho protein compared to the group of intact animals during immunofluorescence analysis. In the group treated with the GABA derivative succicard, there was an improvement in the functional state of the kidneys, accompanied by a significant increase (p≤0,0001) in the area of Klotho-positive material in the epithelium of the convoluted tubules of the kidney in relation to the group of animals with prolonged hyperglycemia without treatment. Conclusion. Prolonged hyperglycemia causes severe renal dysfunction in rats with streptozotocin diabetes: an increase the proteinuria and serum creatinine levels is accompanied by a decrease in the expression of Klotho protein in the kidneys. The GABA derivative succicard with course administration improves kidney function and this effect is accompanied by an increase in the expression of Klotho protein.

Protective Effect of Black Seed and Lettuce Oils Against Paracetamol-Induced Hepatotoxicity in Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; The liver is one of the organs that play an essential role in the human body, including supporting metabolism, immune functions, digestive system, detoxification, storage of vitamins and other functions. This investigation aimed to study the protective effects of black seed and lettuce oil against hepatotoxicity as induced by paracetamol in experimental rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; Twenty male Sprague-Dawley albino rats weighing 150±5 g were divided randomly into four groups (5 rats each) and distributed as follows; 1st group was controlled negative (C -ve group), 2nd group controlled positive (orally administered with 500 mg/kg b.wt., paracetamol), 3rd and 4th groups were orally administered with black seed oil and lettuce oil at a dose of 1 mL/kg b.wt., each) as a preventive dose. All rats were sacrificed and blood was collected for biochemical analysis and then statistically analyzed. &lt;b&gt;Results:&lt;/b&gt; The rat administered with black seed and lettuce oils enhanced body weight gain, food intake and feed efficiency ratio. Moreover, exhibited a significant reduction in the liver enzymes AST, ALT, ALP and TBIL. Meanwhile, black seed and lettuce oils significantly improved kidney functions, lipid profiles and some immune biomarkers including creatine kinase (CK), Creatine Kinase-MB (CK-MB) and Lactate Dehydrogenase (LDH). &lt;b&gt;Conclusion:&lt;/b&gt; This study revealed that the oils of black seed (&lt;i&gt;Nigella sativa&lt;/i&gt;) and lettuce (&lt;i&gt;Lactuca sativa&lt;/i&gt;) have a protective role in improving body weight gain, food intake, feed efficiency ratio, liver enzymes, kidney functions, lipid profiles and some immune biomarkers against paracetamol-induced hepatotoxicity in experimental rats.

Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure.

The function of the respiratory chain is closely associated with kidney function, and the dysfunction of the respiratory chain is a primary pathophysiological change in chronic kidney failure. The incidence of chronic kidney failure caused by defects in respiratory-chain-related genes has frequently been overlooked. Correcting abnormal metabolic reprogramming, rescuing the "toxic respiratory chain", and targeting the clearance of mitochondrial reactive oxygen species are potential therapies for treating chronic kidney failure. These treatments have shown promising results in slowing fibrosis and inflammation progression and improving kidney function in various animal models of chronic kidney failure and patients with chronic kidney disease (CKD). The mitochondrial respiratory chain is a key target worthy of attention in the treatment of chronic kidney failure. This review integrated research related to the mitochondrial respiratory chain and chronic kidney failure, primarily elucidating the pathological status of the mitochondrial respiratory chain in chronic kidney failure and potential therapeutic drugs. It provided new ideas for the treatment of kidney failure and promoted the development of drugs targeting the mitochondrial respiratory chain.

“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy

IntroductionPost-transplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3-14% of kidney transplants (KT), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first three months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA. MethodsWe retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA. ResultsKidney biopsy was performed in 91.1% of patients and complement genetic study in 64.4%. 85.4% of kidney biopsies showed signs of TMA; genetic analysis revealed one pathogenetic variant, two variants of uncertain significance, one likely benign variant, 8 risk polymorphisms, 27 risk haplotypes.After two weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After six months, 28.8% of patients had a complete renal recovery while 44.4% had a partial recovery. ConclusionThis is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.

Oleoylethanolamide attenuates acute-to-chronic kidney injury: in vivo and in vitro evidence of PPAR-α involvement

Chronic kidney disease (CKD) development after acute kidney injury (AKI) involves multiple mechanisms, including inflammation, epithelial-mesenchymal transition (EMT), and extracellular matrix deposition, leading to progressive tubulointerstitial fibrosis. Recently, a central role for peroxisome-proliferator activated receptor (PPAR)-α has been addressed in preserving kidney function during AKI. Among endogenous lipid mediators, oleoylethanolamide (OEA), a PPAR-α agonist, has been studied for its metabolic and anti-inflammatory effects. Here, we have investigated OEA effects on folic acid (FA)-induced kidney injury in mice and the underlying mechanisms. OEA improved kidney function, normalized urine output, and reduced serum BUN, creatinine, and albuminuria. Moreover, OEA attenuated tubular epithelial injury, as shown by histological analysis, and decreased expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Gene expression analysis of kidney tissue indicated that OEA limited immune cell infiltration and inflammation. Moreover, OEA significantly inhibited Wnt7b and Catnb1 gene transcription and α-smooth muscle actin expression, indicating suppression of EMT. Accordingly, OEA exhibited an anti-fibrotic effect, as shown by Masson staining and the reduced levels of transforming growth factor (TGF)-β1, fibronectin, and collagen IV. Mechanistically, the nephroprotective effect of OEA was related to PPAR-α activation since OEA failed to exert its beneficial activity in FA-insulted PPAR-α-/- mice. PPAR-α involvement was also confirmed in HK2 cells where GW6471, a PPAR-α antagonist, blunted OEA activity on the TGF-β1 signalling pathway and associated pro-inflammatory and fibrotic patterns. Our findings revealed that OEA counteracts kidney injury by controlling inflammation and fibrosis, making it an effective therapeutic tool for limiting AKI to CKD progression.

Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation

&lt;p&gt;Diabetic kidney disease (DKD), a severe diabetic complication affecting approximately one-third of diabetic patients, is the leading cause of end-stage chronic kidney disease. The benefits of regular exercise for patients with DKD have been well documented, particularly in overweight patients with DKD. However, the underlying mechanisms are incompletely understood. The present study demonstrates that exercise improves kidney function in diabetic &lt;i&gt;db/db&lt;/i&gt; mice through activating PPARδ-mediated fatty acid β-oxidation (FAO). Twelve-week treadmill running exercise improved kidney function in &lt;i&gt;db/db&lt;/i&gt; mice. Metabolomics and transcriptomics profiling analysis collectively revealed that dysregulation of FAO in &lt;i&gt;db/db&lt;/i&gt; mice was largely corrected by running exercise. KEGG pathway enrichment revealed that PPAR pathway, a critical signalling cascade in FAO and exercise, is involved in DKD, suggesting PPARδ activation protects renal function through promoting FAO. Which was confirmed by improved renal function and enhanced FAO in &lt;i&gt;db/db&lt;/i&gt; mice treated with PPARδ agonist GW501516. Oppositely, PPARδ-specific inhibitor GSK0660 abolished exercise-mediated improvement in renal function and FAO. In combining with gene expression profiling data we identified CPT1α, the rate-limiting enzyme in fatty acid oxidation, was suppressed in the kidney of diabetic mice and reversed by exercise and the PPARδ agonist GW501516. The findings hint at a potential role for the PPARδ-CPT1α pathway in exercise-induced improvements in diabetic renal function and may warrant further exploration of the PPARδ-CPT1α pathway as a therapeutic target in DKD.&lt;/p&gt;