Elevated Serum Urea Research Articles

Pathological Fracture of Multiple Myeloma with CRAB Criteria: A Case Report

Multiple myeloma (MM) is a malignancy of plasma cells, often preceded by an asymptomatic condition known as the precursor state of monoclonal gammopathy of undetermined significance (MGUS). The diagnosis of multiple myeloma is typically confirmed using the CRAB criteria, which include hypercalcemia, renal impairment characterized by elevated serum urea and creatinine levels, anemia, and bone abnormalities. We report a rare case of multiple myeloma in a 63-year-old male patient who presented with pain in his left hand following a fall against a wall. Clinical and radiological examinations revealed findings consistent with multiple myeloma, with a differential diagnosis including metabolic bone disease and metastatic bone disease

Attenuation of inflammation, oxidative stress and TGF-β1/Smad3 signaling and upregulation of Nrf2/HO-1 signaling mediate the protective effect of diallyl disulfide against cadmium nephrotoxicity

Heavy metals are toxic environmental pollutants with serious health effects on humans and animals. Cadmium (Cd) is known for its serious nephrotoxic effect and its toxicity involves oxidative stress (OS) and inflammation. Diallyl disulfide (DADS), a main constituent of garlic, exhibited cytoprotective and antioxidant activities. This study investigated the effect of DADS on OS, inflammation, and fibrosis induced by Cd in rat kidney, pointing to the involvement of transforming growth factor-β (TGF-β)/Smad3 and nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, and peroxisome proliferator-activated receptor gamma (PPARγ). Rats received DADS for 14 days and Cd on day 7 and blood and kidney samples were collected. Cd elevated serum creatinine, urea and uric acid, provoked kidney histopathological alterations and collagen deposition, increased kidney malondialdehyde (MDA) level, and decreased glutathione (GSH) and antioxidant enzymes. Nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and CD68 were upregulated in Cd-administered rat kidney. DADS prevented kidney injury, mitigated OS, suppressed NF-κB, CD68 and pro-inflammatory mediators, and boosted antioxidants. DADS downregulated TGF-β1, Smad3 phosphorylation and Kelch-like ECH-associated protein-1 (Keap1), and increased Nrf2, HO-1, cytoglobin, and PPARγ. In conclusion, DADS protects the kidney against Cd toxicity by attenuating OS, inflammation, and TGF-β1/Smad3 signaling, and enhancement of Nrf2/HO-1 signaling, antioxidants, and PPARγ.

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.

Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Background: Peptic ulcers are increasingly reported as a challenging disease in clinical settings. Several medications are employed in the management of peptic ulcers. Thus far, there is no medication devoid of any adverse effects that may achieve a 100% curative rate or provide a total remedy for the ailment. Aim: We aimed to examine the healing effects of trimetazidine against indomethacin-induced gastric ulcers in albino rats. Methodology: A total of 25 rats were used, divided into five groups (each group contained five rats): a negative control group that was only treated with distilled water, a positive control group that was only treated with a single dose of indomethacin (30 mg/kg) orally, a group that received indomethacin (30 mg/kg) and low doses of trimetazidine (17.5 mg/kg) orally, a group that received indomethacin (30 mg/kg) and medium doses of trimetazidine (35 mg/kg) orally, and a group that received indomethacin (30 mg/kg) and high doses of trimetazidine (52.5 mg/kg) orally. The induction of gastric ulcers occurred on the first day of the experiment through the administered indomethacin and, subsequently, the rats were treated orally with either trimetazidine or distilled water, three times daily, for 7 days. Serum urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels were measured. Stomachs were excised from the rats’ bodies and opened along the greater curvature; they were then rinsed with saline, extended on a white corkboard, and examined macroscopically. The stomach tissues were also processed in order to generate microscopic slides for microscopical examination. Results: Indomethacin administration caused multiple ulcerations in the gastric mucosa, significant elevations in serum urea, creatinine, AST, and ALT levels, and a significant reduction of the serum albumin levels. The treatment with trimetazidine significantly healed the indomethacin-induced gastric ulcers. Conclusion: The present study indicates that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin can induce substantial gastric ulcers, which may be linked to a direct toxic effect on the histological architecture of the gastric linings in addition to the reduction of blood flow to gastric mucosa; this effect can be treated by administration of trimetazidine. Ultimately, this study suggests that administering the optimal dosage of trimetazidine can be advantageous in treating stomach ulcers caused by NSAIDs. Moreover, the study suggests that the indomethacin-induced liver and renal dysfunction can also be alleviated by the use of trimetazidine.

Modulatory Effect of Ginseng Extracts against Trafos Cu Plant Growth Regulators Induced Renal Toxicity in Rats

Background: Plant growth regulators (PGRs) are widely used as pesticides that can induce toxicity to industrial workers and farmers directly by inhalation during use in agriculture and indirectly through food that have been sprayed with PGRs. Therefore, this work intends to investigate the protective and therapeutic effects of ginseng extracts against Trafos Cu induced kidney toxicity, DNA fragmentation, oxidative stress, and PCNA expression alterations. Methods: A total of 60 male rats divided into 6 groups [Gp1, control; Gp2, ginseng; Gp3, Trafos Cu; Gp4, Ginseng+ Trafos Cu; Gp5, Trafos Cu+Ginseng; Gp6, Self-treated. Result: Current findings revealed that rats treated with Trafos Cu (Gp3 and Gp6) induced a significant elevation in serum urea, creatinine, sodium, potassium, chloride and renal injury, DNA damage, MDA, PCNA, TNFα expressed and a significant depletion in calcium, GSH, and catalase levels as compared to control. Treatments of Trafos Cu with Ginseng (Gp4 and Gp5) induced improvements in kidney functions and structure with best results for Gp5. Ginseng has the capacity to mitigate the renal toxicity induced by Trafos Cu in male albino rats.

A field study to optimize protein and lipid levels in diet for cage-cultured subadult rockfish Sebastes schlegelii

A feeding trial was conducted to evaluate growth, body composition, serum biochemistry, digestion and metabolism, and oxidation resistence of S. schlegelii fed 9 diets in a 3×3 factorial design (protein levels: 44 %, 48 %, 52 %; lipid levels: 6 %, 10 %, 14 %), to optimize protein and lipid levels for practical feed formula. Rockfish (114.25 g) were stocked into 27 cages in an offshore system and fed test diets to satiation twice daily for 8 weeks. Growth increased but feed conversion rate decreased with dietary protein increasing. Increasing dietary protein to >48 % led to reduced feeding intake but increased protein efficiency ratio. Lipid efficiency ratio increased with dietary protein increasing but decreased with dietary lipid increasing. Hepatosomatic index decreased coupling with the increases in condition factor and liver lipid content as dietary lipid increased to 14 %. Intraperitoneal fat ratio increased with dietary lipid increasing. Increasing dietary protein to > 48 % significantly elevated serum total protein and glucose concentrations, hepatic glycogen synthase activity. High-protein (52 %) diets elevated serum albumin and urea nitrogen concentrations, hepatic pyruvate kinase and alanine aminotransferase (ALT) activities but downregulated hepatic growth-hormone (GH) receptor. Activities of trypsin, lipase, serum superoxide dismutase and total antioxidant capacity decreased with the dietary lipid increasing. Increasing dietary lipid to > 10 % reduced serum GH concentration, and high-lipid (14 %) diets significantly enhanced serum triglyceride concentration and hepatic transaminases activities, and resulted in a visual increase of adipocytes in liver. Serum cholesterol and low-density lipoprotein decreased as dietary protein increased to 48–52 % or dietary lipid >10 %. Hepatic succinate dehydrogenase activity and serum IGF-1 significantly increased while hepatic fatty acid synthetase decreased as dietary protein increased to >48 % or dietary lipid >10 %. High-protein (52 %) diet or high-lipid (14 %) diet elevated serum malonaldehyde concentration. These findings suggested 48 % protein and 10 % lipid were the optimal in diet for subadult S. schlegelii.

Neurological Manifestation of Neonatal Acute Kidney Injury: Focusing on the Clinico-Radiological Profile.

Purpose This study aimed atstudying the neurological manifestation of neonatal acute kidney injury, focusing on the clinico-radiological profile. Methodology In this cross-sectional study, newborns hospitalized in the neonatal intensive care unit of a tertiary care hospital were enrolled over a study period of one year. As per the Kidney Disease: Improving Global Outcome (KDIGO) criteria, 74 neonates were enrolled, and magnetic resonance imaging (MRI) was performed on the same neonates. Result In this study, acute kidney injury (AKI) was seen more often in neonates with admission weights between 1,500 and 2,499 grams, accounting for 52.7% of total study participants. In the current study, neonates admitted with AKI presented more with signs and symptoms of encephalopathy, such as lethargy (78.4%), seizures (64.8%), and irritability (35.1%) at admission. Signs and symptoms of fever and decreased urine output were more common after the first week of life. Abnormal MRI findings were observed in 64.9% of neonates with AKI. The mean blood urea and serum creatinine levels in neonates with abnormal MRI were 188.14 ± 108.25 mg/dL and 2.93 ± 2.16 mg/dL, respectively. The mean blood urea and serum creatinine levels in neonates with normal MRI were 169.84 ± 65.45 mg/dL and 2.41 ± 1.85 mg/dL, respectively. Of the 74 neonates enrolled with AKI, 12 (16.21%) had CSVT. These neonates had a mean blood urea level of 231.58 ± 111.66 mg/dL (p = 0.047) and a mean creatinine level of 3.77 ± 2.78 mg/dL. Conclusion Neonatal AKI has a variable presentation with high mortality and morbidity. Elevated serum urea and creatinine can be used to predict CSVT.

Farnesol attenuates cadmium-induced kidney injury by mitigating oxidative stress, inflammation and necroptosis and upregulating cytoglobin and PPARγ in rats

Heavy metals are environmental pollutants that can harm animals and humans even at low concentrations. Cadmium (Cd) is known for its serious health effects on different organs and its toxicity is associated with oxidative stress (OS) and inflammation. Farnesol (FAR), a sesquiterpene alcohol found in many vegetables and fruits, possesses promising anti-inflammatory and antioxidant activities. This study evaluated the effect of FAR on Cd-induced kidney injury, pinpointing its effect of the redox status, inflammation, fibrosis and necroptosis. Rats in this study received FAR for 14 days and Cd on day 7. Elevated serum creatinine, urea and uric acid, and several kidney histopathological alterations were observed in Cd-administered rats. Cd increased MDA, decreased antioxidants, downregulated PPARγ and upregulated NF-κB p65, IL-6, TNF-α, and IL-1β. Necroptosis mediators (RIP1, RIP3, MLKL, and caspase-8) and α-SMA were upregulated, and collagen deposition was increased in Cd-administered rats. FAR ameliorated kidney injury markers and tissue damage, attenuated OS, suppressed NF-κB and inflammatory mediators, and enhanced antioxidants. In addition, FAR suppressed RIP1, RIP3, MLKL, caspase-8, and α-SMA, and enhanced kidney cytoglobin and PPARγ. In conclusion, FAR protects against Cd nephrotoxicity by suppressing OS, inflammatory response and necroptosis, effects associated with enhanced antioxidants, cytoglobin, and PPARγ.

Ameliorating and Therapeutic Impact of Curcumin Nanoparticles Against Aluminum Oxide Nanoparticles Induced Kidney Toxicity, DNA Damage, Oxidative Stress, PCNA and TNFα Alteration in Male Rats.

Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Combined Rupture of the Diaphragm and Urinary Bladder in Blunt Trauma Abdomen.

The authors examined a 25-year-old man with a combined rupture of the diaphragm and urinary bladder following blunt trauma to the abdomen. The presence of hematuria, suprapubic tenderness, and elevated serum urea and creatinine levels in this patient raised suspicion of urinary bladder rupture. Documentation of bowel gas shadows on the chest x-ray suggested underlying diaphragm injury. A computed tomogram of the thorax and abdomen confirmed the tear in the left hemidiaphragm with intrathoracic herniation of abdominal contents; however, it failed to detect the intraperitoneal urinary bladder rupture. Both the defects were identified and repaired during laparotomy. The sudden increase in intraabdominal pressure in blunt trauma to the abdomen often resulted in full-thickness tears of the diaphragm and the urinary bladder. Although radiological investigations were pivotal for assessing the damage to the internal organs, a methodical and thorough exploratory laparotomy was invaluable for successfully managing patients with blunt abdominal trauma.

Marginal Zinc Deficiency Promotes Pancreatic Islet Enlargement While Zinc Supplementation Improves the Pancreatic Insulin Response in Zucker Diabetic Fatty Rats.

Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to β-cell exhaustion.

Predictors of persistent postpartum hypertension among women with hypertensive disorders of pregnancy: A prospective cohort study

BackgroundPersistent postpartum hypertension in women with hypertensive disorders of pregnancy (HDP) may indicate a progression towards chronic hypertension. This study aimed to determine the prevalence and identify the predictors of persistent hypertension at six weeks after delivery among women with HDP in Vietnam. MethodsA prospective cohort study was conducted at the National Hospital of Obstetrics and Gynecology in Vietnam from March 2023 to October 2023. Our study population included women with HDP who were 18 years or above and delivered after 22 weeks of gestation. Participants were enrolled within 24 h of delivery and followed up to six weeks after delivery. Persistent hypertension was defined as a systolic blood pressure (BP) of ≥140 mm Hg or a diastolic BP of ≥90 mm Hg or receiving anti-hypertensive medications at six weeks postpartum. Bivariate and multivariable logistic regression analyses were performed to identify the predictors. ResultsOf the 343 participants initially enrolled, 293 were successfully followed up (follow-up rate 85.4 %). Among women with HDP, 10.9 % experienced persistent hypertension at six weeks after delivery. Specifically, 7.7 % of women with gestational hypertension and 11.8 % of those with preeclampsia – eclampsia remained hypertensive at this time point. Maternal age of 35 years or older, elevated serum urea level (>6.7 μmol/l), and hypertension at seven days after delivery were identified as independent predictors of persistent postpartum hypertension. ConclusionApproximately one in ten women with HDP in our study remained hypertensive at six weeks after delivery. It is crucial to implement effective strategies for identifying these women and providing timely interventions to control BP and reduce the risk of future cardiovascular complications following HDP.

Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway.

The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and creatinine served as indicators of renal function. Our results indicated that LPS injection induced renal function deterioration, evidenced by elevated serum urea and creatinine levels compared to control mice. However, pretreatment with limonene at doses of 100 and 200 mg/kg mitigated this decline in renal function, evidenced from the reduced levels of serum urea and creatinine. Limonene demonstrated anti-inflammatory effects by reducing pro-inflammatory cytokines (TNF-α, IL-1β, COX-2), suppressing the TLR4/NF-κB/AP-1 but not IRF3 signaling pathways, and modulating oxidative stress through Nrf2 activation. The results suggest that limonene holds promise as a potential therapeutic agent for mitigating intestinal inflammation and preserving gastrointestinal health.

Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney

BackgroundMacrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters.MethodsUsing immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients.ResultsThe frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease.ConclusionAlthough M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study

BackgroundRhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group.ResultsBlood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment.ConclusionsTreatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Therapeutic potential of black seed oil in treating rheumatoid arthritis: Insights on biochemical and genetic analyses of inflammatory signaling transducer

Nigella sativa (Black seed) has been a longstanding component of traditional medicine. Rheumatoid arthritis, an autoimmune disorder targeting bone, cartilage, and synovial cells, leads to enduring joint damage due to pathological immune responses. This study aims to assess the effectiveness of black seed oil in treating rheumatoid arthritis using a rat model. Fifty male albino rats were randomly assigned to five groups: control, induced arthritis, induced arthritis treated with black seed oil, induced arthritis treated with hydroxychloroquine, and induced arthritis treated with a combination of black seed oil and hydroxychloroquine. Arthritis was induced in the rats using single dose of 0.1 ml of Complete Freunds Adjuvant. Biochemical and genetic analyses of signaling transducers (IFNγ, IL-4, STAT3, and IL-12) were conducted on blood samples and stifle joints. Results indicated that induced arthritis led to elevated serum AST, ALT activities, creatinine, urea, FBS, RF, Anti-CCP, and CRP, along with reduced serum TAC. Additionally, there was an upregulation of IL-12, IFNγ, and STAT3 genes, and a downregulation of IL-4 gene compared to the normal control group. Treatment with black seed oil or hydroxychloroquine individually demonstrated notable improvements in these parameters, although the combined treatment showed less marked improvement. In conclusion, black seed oil demonstrates potential therapeutic benefits in alleviating the negative impacts of rheumatoid arthritis.

Proteinuria is a clinical characteristic of intrahepatic cholestasis of pregnancy but it is not a marker of severity: A retrospective cohort study.

To determine the prevalence of proteinuria in patients diagnosed with intrahepatic cholestasis of pregnancy (IHCP), and the association between the presence of proteinuria and adverse pregnancy outcomes. This was a retrospective cohort study. The study included all pregnant patients between July 2014 and January 2022, at gestational age > 24weeks who had been diagnosed with IHCP and had completed a 24-hour protein collection. High order multifetal gestations were excluded. Patients were divided into 3 groups:1. IHCP without proteinuria (Non-proteinuric group);2. IHCP with proteinuria and normal blood pressure (Isolated proteinuria group), and 3. IHCP with proteinuria and elevated blood pressure (IHCP with preeclampsia (PET)). Primary outcome was defined as a composite maternal-fetal outcome including: preterm labor <34 weeks, arterial cord blood ph<7.1, rate of Cesarean delivery due to non-reassuring fetal monitoring. Parametric and non-parametric statistical methods were used for analysis. A total of 272 met all inclusion criteria and were included, 94 patients (34.5%) had proteinuria; of them, 67 (24.6%) had isolated proteinuria and 27 (9.9%) had PET. Demographic parameters were comparable among the groups. Patients with PET had higher rates of in-vitro fertilization (IVF) treatments, twin gestation and elevated serum creatinine and urea levels. The rate of composite adverse pregnancy outcome was higher in patients with PET compared with patients with and without proteinuria (14/27 (51.9%) vs. 18/67 (26.9%) vs. 49/178 (27.5%), respectively, p = 0.03). Approximately 35% of patients with IHCP have proteinuria. The presence of PET, rather than isolated proteinuria, is associated with adverse pregnancy outcome.

Involvement of Nrf2, JAK and COX pathways in acetaminophen-induced nephropathy: Role of some antioxidants

ObjectivesAcetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury. Design and methodRats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP. ResultsTreatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree. ConclusionThe combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.

Vitamin D receptor (BsmI) gene polymorphism and allele frequency among chronic kidney disease patients in south Indian population.

The vitamin D receptor (VDR) axis plays an important role in multiple physiological renal functions. BsmI gene is one among the VDR gene plays a vital role in maintaining this VDR axis and any polymorphism in VDR gene will cause dysfunction of renal tissues. The main objective of the study is to study the link between BsmI VDR gene polymorphism and Chronic Kidney Disease (CKD). This was a case-control study, which includes 100 cases and 100 controls. BsmI gene analysis was done by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Among 100 CKD study participants, BB (wild-type) genotype of BsmI gene was present in 7 patients (7%), Bb (heterozygous) genotype was present in 23 patients (23%) and bb (mutant) genotype was present in 70 patients (70%). And among 100 controls, 92 subjects were found to have BB genotype and 8 subjects were found to have Bb genotype and none of subjects were found to have bb genotypes. CKD patients with Bb and bb genotypes were found to have significantly elevated serum urea, creatinine and decreased Glomerular Filtration Rate (GFR) when compared to the BB genotype of BsmI gene. 'b' allele of BsmI gene, Bb and bb genotypes of BsmI gene plays a greater role in Guanine/Adenine single nucleotide polymorphism of BsmI gene in CKD.