Acute Renal Damage Research Articles

Novel insights into the augmented effect of curcumin and liraglutide in ameliorating cisplatin-induced nephrotoxicity in rats: Effects on oxidative stress, inflammation, apoptosis and pyroptosis via GSK-3β

Cisplatin dose-dependent nephrotoxicity is a major issue limiting its proper use in cancer treatment. Inflammation, redox imbalance, and dysregulated cell death are the most plausible underlying pathomechanics. Curcumin and the glucagon-like peptide-1 receptor agonist, liraglutide, have been investigated in various experimental models for their antioxidant, anti-inflammatory, and cell death modulatory effects. Hence, this work was designed to investigate curcumin and liraglutide nephroprotective effects and how they behave together against cisplatin-induced acute kidney injury (AKI) in an experimental Wistar rat model. The study comprised 61 rats divided randomly into 6 unequal groups: control I and II, cisplatin-induced nephrotoxicity, curcumin-treated, liraglutide-treated, and co-treated groups. Renal index, serum nephrotoxicity markers (Cr, BUN, NGAL), renal glycogen synthase kinase-3 β (GSK-3β), oxidant/antioxidant parameters (MDA, MPO, GSH, NQO1, HO-1), and inflammatory biomolecules (TNF-α, IL-1β) were assayed. Moreover, renal cleaved-caspase3 and the pyroptotic biomolecules (nod-like receptor family pyrin domain containing 3, gasdermin D N-terminal fragment) were immunoassayed. Furthermore, relative renal expression of both nuclear factor erythroid 2-related factor 2 (Nr-F2) and caspase1 was evaluated by qRT-PCR. Histopathological examination of renal tissue was carried out along with detection of Bcl-2 and Bax immunoreactivity. Cisplatin induced acute renal damage, augmented inflammation, dysregulated redox balance and induced apoptosis and pyroptosis. On the other hand, curcumin and liraglutide corrected the dysregulated mechanisms and normalized results to a great extent. Mutual use of curcumin and liraglutide exerted the greatest effect in the co-treatment group. Nr-F2/HO-1 axis and GSK-3β play a master role in their nephroprotective effect. In conclusion, curcumin and liraglutide have an ameliorative effect against cisplatin-induced nephrotoxicity and can be used alone or better in combination owing to their augmented effect launching promising avenues for cancer patients under cisplatin treatment, retarding AKI and enabling them to gain the best protocol effectiveness.

Tumor Markers as Predictors of Acute Kidney Injury Incidence and Staging of the Muscle-Invasive Bladder Cancer Receiving Chemoradiation Therapy.

Bladder cancer, as one of types of cancers within the urinary tract, is associated with a greater risk of acute kidney injury (AKI), resulting in a poorer prognosis, discontinuation of effective oncological treatments, longer hospitalization, and higher expenses. There is no discussion yet on tumor markers in bladder cancer. With the revolutionary advances in bladder cancer molecular subtyping over the past decade, the presence of tumor markers to assess the staging of bladder cancer has yet to be discussed. In this study, we intended to assess the relationship between tumor markers and incidence of AKI, also between tumor markers and the cancer staging. This retrospective cross-sectional study utilized secondary data from 26 medical records of patients diagnosed with bladder cancer at the Adam Malik and Universitas Sumatera Utara Hospital between 2021and 2022. This study included all patients with bladder cancer who met the inclusion criteria. Continuous variables were reported as mean (standard deviation (SD)) and examined using an independent t-test. Categorical variables were reported as proportions, examined using Chi-square or Fisher's exact test. Pre- and post-tumor marker data were evaluated with dependent sample t-test for normal variance data, and Wilcoxon test for data with atypical distribution. P values were set at 0.05. CD44 (P = 0.003) and programmed cell death 1 (PD-1) (P = 0.030) were the only significant markers in their pre- and post-chemoradiation states among the four investigated tumor markers in this study. Meanwhile, PD-1 tumor marker levels were only found to be significant between AKI and pre-chemoradiation (P = 0.011). Even though the multivariate study of tumor staging did not show any statistical significance, both tumor markers CD44 and PD-1 showed a significant effect on the incidence of acute renal damage (P = 0.034). Pre-chemoradiation PD-1 tumor markers showed promise as good predictive indicators for staging and AKI incidence in muscle-invasive bladder cancer patients undergoing chemoradiation therapy.

Évaluation post-transplantation précoce de la dysfonction aiguë du greffon rénal

AbstractKidney transplantation is the best option in the treatment of end-stage kidney disease. Early acute kidney transplant dysfunction is a common complication that corresponds to acute renal failure (AKI) postoperatively after renal transplantation. When it occurs, it favors acute rejection and chronic dysfunction of kidney transplant. Incidence of this complication is constantly rising due to the increased use of grafts from extended criteria donors and from donors after circulatory death. This acute renal failure clinically results in a persistent elevation of serum creatinine and possibly a decrease in diuresis and the need for dialysis during the first postoperative week. However, these signs of renal damage are mostly inefficient and lead to a late diagnosis, limiting treatment efficiency. Therefore, it is essential to develop and use new methods for evaluating acute renal damage early after kidney transplantation. This review explores the various established or developing diagnostic modalities for early AKI after kidney transplantation, whether glomerular filtration rate (GFR) assessment methods or other approaches.

Metformin: A New Inhibitor of the Wnt Signaling Pathway in Cancer.

The biguanide drug metformin is widely used in type 2 diabetes mellitus therapy, due to its ability to decrease serum glucose levels, mainly by reducing hepatic gluconeogenesis and glycogenolysis. A considerable number of studies have shown that metformin, besides its antidiabetic action, can improve other disease states, such as polycystic ovary disease, acute kidney injury, neurological disorders, cognitive impairment and renal damage. In addition, metformin is well known to suppress the growth and progression of different types of cancer cells both in vitro and in vivo. Accordingly, several epidemiological studies suggest that metformin is capable of lowering cancer risk and reducing the rate of cancer deaths among diabetic patients. The antitumoral effects of metformin have been proposed to be mainly mediated by the activation of the AMP-activated protein kinase (AMPK). However, a number of signaling pathways, both dependent and independent of AMPK activation, have been reported to be involved in metformin antitumoral action. Among these, the Wingless and Int signaling pathway have recently been included. Here, we will focus our attention on the main molecular mechanisms involved.

Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury

PurposeGlobally, sepsis, which is a major health issue resulting from severe infection-induced inflammation, is the fifth biggest cause of death. This research aimed to evaluate, for the first time, the molecular effects of gabapentin's possible nephroprotective potential on septic rats by cecal ligation and puncture (CLP).MethodsSepsis was produced by CLP in male Wistar rats. Evaluations of histopathology and renal function were conducted. MDA, SOD, GSH, TNF-α, IL-1β, and IL-6 levels were measured. qRT-PCR was utilized to determine the expression of Bax, Bcl-2, and NF-kB genes. The expression of Nrf-2 and HO-1 proteins was examined by western blotting.ResultsCLP caused acute renal damage, elevated the blood levels of creatinine, BUN, TNF-α, IL-1β, and IL-6, reduced the expression of Nrf-2 and HO-1 proteins and the Bcl-2 gene expression, and upregulated NF-kB and Bax genes. Nevertheless, gabapentin dramatically diminished the degree of the biochemical, molecular, and histopathological alterations generated by CLP. Gabapentin reduced the levels of proinflammatory mediators and MDA, improved renal content of GSH and SOD, raised the expression of Nrf-2 and HO-1 proteins and Bcl-2 gene, and reduced the renal expression of NF-kB and Bax genes.ConclusionGabapentin mitigated the CLP-induced sepsis-related acute kidney injury through up-regulating Nrf-2/HO-1 pathway, repressing apoptosis, and attenuating the oxidative stress status by reducing the levels of the proinflammatory mediators and enhancing the antioxidant status.

SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage.

Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. Materials and Methods: Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. Results: The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2-related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. Conclusions: OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage.

RENAL10: Urinary Vitamin D Binding Protein and Kidney Injury Molecule-1 May Predict the Risk of Acute Kidney Injury in Heart Failure Patients Undergoing CF-LVAD Implantation

Background: Renal dysfunction in advanced heart failure (HF) and durable mechanical circulatory support (MCS) is common and harmful, yet current tests are inaccurate and confounded by body composition, fluid status, and other factors. Newer biomarkers more directly reflecting specific aspects of renal health/function have been tested in other fields but have yet to be tested in this complex setting. Urine vitamin-D-binding protein (uVDBP) and urine kidney injury molecule-1 (uKIM-1) have been shown to identify and stage severity of parenchymal kidney injury in several settings. The purpose of our study is to explore the potential role of uVDBP and uKIM-1 as biomarkers of acute renal damage among HF patients receiving CF-LVAD support. Methods: Our cohort included 29 HF patients undergoing CF-LVAD implantation. Early morning voided urine was collected immediately pre-implantation. Measurements of uVDBP and uKIM-1 were performed with ELISA kits and data were normalized to urine creatinine (ng/mg Cr.). Relationships of uVDBP and uKIM-1 and important baseline clinical characteristics (presence of kidney dysfunction, defined as eGFR<60 ml/min/1.73m2, and hemodynamic instability, defined as INTERMACS 1/2) were assessed using the Wilcoxon test. Relationships of baseline uVDBP and uKIM-1 (log2 transformed) with risk of acute kidney Injury (AKI) developing within 90 days after CF-LVAD implant were assessed, using logistic regression with adjustment for baseline kidney function and for baseline hemodynamic stability. AKI was assessed using RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Results: The cohort (n=29), had mean (SD) age 58 (14) years, 17.2% were female, and destination therapy goal for 96.6%. Baseline kidney dysfunction and hemodynamic instability were present in 37.9% and 44.8% of patients respectively, and 44.8% had AKI within 90 days. Baseline uVDBP [median (IQR)] was 0.88 (0.20-2.3) ng/mg Cr., and baseline uKIM-1 [median (IQR)] was 0.013 (0.0032-0.042) ng/mg Cr. Baseline uVDBP was found to be significantly associated with baseline kidney risk category (p <0.001), with higher uVDBP associated with worse baseline kidney health/function risk (assessed by combination of baseline low kidney function and hemodynamic instability, Fig.1A). Baseline uKIM-1 was significantly associated with baseline kidney function but not with baseline kidney risk category (Fig.1B). Two-fold higher baseline uKIM-1 was associated with nearly two-fold increased odds of 90-day AKI (Table.1). Similar results were obtained for baseline uVDBP. Conclusions: We have demonstrated that both uVDBP and uKIM-1 may provide additional information about baseline kidney health beyond that provided by serum creatinine-based and hemodynamic instability-based measures, assessed by risk for adverse 90-day kidney outcomes. Further study in larger cohorts is needed. Table 1. - Association of baseline urine markers with post-implant AKI Odds ratios (95% confidence intervals) Unadjusted Model 1 Model 2 uKIM-1 Per two-fold greater uKIM-1 1.98 (1.28-3.71) 4.39 (1.79-22.2) 8.76 (2.03-311) uVDBP Per two-fold greater uVDBP 1.99 (1.27-3.68) 2.25 (1.23-4.90) 7.74 (2.07-296) Model 1 was adjusted for baseline kidney dysfunction;Model 2 was adjusted for baseline kidney dysfunction and baseline hemodynamic instability

Urinary microRNAs in sepsis function as a novel prognostic marker.

Renal dysfunction is a common complication of sepsis. Early diagnosis and prompt treatment of sepsis with renal insufficiency are crucial for improving patient outcomes. Diagnostic markers can help identify patients at risk for sepsis and AKI, allowing for early intervention and potentially preventing the development of severe complications. The aim of the present study was to investigate the expression difference of urinary microRNAs (miRNAs/miRs) in elderly patients with sepsis and secondary renal insufficiency, and to evaluate their diagnostic value in these patients. In the present study, RNA was extracted from urine samples of elderly sepsis-related acute renal damage patients and the expression profiles of several miRNAs were analyzed. In order to evaluate the expression profile of several miRNAs, urine samples from elderly patients with acute renal damage brought on by sepsis were obtained. RNA extraction and sequencing were then performed on the samples. Furthermore, multiple bioinformatics methods were used to analyze miRNA profiles, including differential expression analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of different miRNA target genes, to further explore miRNAs that are suitable for utilization as biomarkers. A total of four miRNAs, including hsa-miR-31-5p, hsa-miR-151a-3p, hsa-miR-142-5p and hsa-miR-16-5p, were identified as potential biological markers and were further confirmed in sepsis using reverse transcription-quantitative PCR. The results of the present study demonstrated that the four urinary miRNAs were differentially expressed and may serve as specific markers for prediction of secondary acute kidney injury in elderly patients with sepsis.

Intensive receptor blockade and plasma exchange to treat refractory scleroderma renal crisis in patients with agonistic autoantibodies targeting the angiotensin II type 1 and endothelin-1 type A receptors

Scleroderma renal crisis is a rare complication of systemic sclerosis characterized by a rapid decline in kidney function due to acute renal vascular injury. Recently, activating autoantibodies targeting the angiotensin II type 1 receptor and the endothelin-1 type A receptor have been implicated in the pathophysiology of scleroderma renal crisis by sensitizing the angiotensin II type 1 receptor and endothelin-1 type A receptor in renal resistance arteries to their natural ligands. Here, we describe a cohort of 10 patients with scleroderma renal crisis refractory to standard treatment, including blockade of the renin-angiotensin system. Multimodal therapy was initiated, targeting at the removal of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies by plasma exchange and the reduction of vasoconstrictive activity. Further treatment options included angiotensin II type 1 receptor and endothelin-1 type A receptor blockade, iloprost, intravenous immunoglobulins, and immunosuppression. Six patients were hypertensive. On kidney biopsy, concentric intimal sclerosis was present in all patients, whereas acute vascular injury was evident in eight. Levels of anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies were significantly reduced by multimodal treatment. Kidney function improved in three patients with histological signs of severe acute renal vascular damage. This report demonstrates that intensive multimodal therapy taking account of potentially pathogenic anti-angiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies in concert with other vasodilatory interventions provides a salvage option for patients with refractory scleroderma renal crisis.

Renal Benefits of CO2 as a Contrast Media for EVAR Procedures: New Perspectives on 1 Year Outcomes

Background and Objectives: Endovascular aneurism repair (EVAR) is a minimally invasive alternative to open surgery for the treatment of abdominal aortic aneurysm. Iodine contrast medium (ICM) is considered the gold standard, at the high price of related nephrotoxicity and allergic reactions. Carbon dioxide (CO2) has been suggested as an alternative non-nephrotoxic contrast media agent. We aimed to evaluate the safety and the renal impact of the administration of CO2, compared with ICM in EVAR procedures. Design, Setting, Participants, and Measurements: We retrospectively reviewed data of patients who underwent EVAR at the Vascular Surgery Department of the Sant’Orsola Hospital in Bologna. Estimated glomerular filtration rate (eGFR) was evaluated before intervention, immediately after and at 12 months. Results: In total, 22 patients received CO2 and low-dose ICM (CO2 Group) and 22 received standard ICM (Control Group), matched for clinical characteristics and renal function at the time of procedure. Pre and post-operative renal function values (eGFR) were compared between the two groups: in the immediate post-operative the group treated with CO2 and low-dose ICM globally showed a slight improvement in renal function (mean eGFR +5.10%±3.2), meanwhile the group treated with standard dose of ICM presented a significant worsening of renal function compared with pre-procedure values (mean eGFR −9.65%±4). Incidence of post-contrast acute kidney injury (PC-AKI) was 9% in the CO2 group vs 27% in the Control group. At 12 months, the renal impairment was significantly greater in the ICM group than in the CO2 group (mean eGFR decrease −19.2%±11.1 and −7.40%±3.5, respectively). Conclusions: Administration of either CO2 alone or along with low-dose ICM showed to be safer than full-dose ICM alone, lowering the incidence of PC-AKI in patients undergoing EVAR. Unexpectedly, our study revealed also a significant worsening of renal function in patients treated with standard dose of ICM in 1-year follow-up, introducing the concept that acute renal damage caused by ICM could elicit a chronic injury process that affect long-term renal outcomes. Clinical Impact Evaluating the safety and the renal impact of the administration of CO2, compared to Iodinate Contrast Medium, in EVAR procedures represents a first step in order to further tayloring medical procedures on patients characteristics. Our findings can guide the clinicians and surgeons in the procedures choice, not considering only the immediate effect of ICM on renal function but also the potential long-term effects.

Glomerulonephritis in Children: Epidemiological, Clinical, Paraclinical and Therapeutic Profile

Background: Glomerulonephritis (GN) is a rare kidney disease that causes significant morbidity and mortality. They are frequently difficult to treat, and in some cases, no treatment is available, and they can progress to chronic kidney disease (CKD) and end stage renal disease (ESKD). Kidney biopsy is the preferred diagnostic method because it helps determine the precise specific diagnosis, assesses the level of disease activity and severity, and thus aids in proper therapy and prognosis prediction. Methods: Retrospective review of 40 children under the age of 15 with GN diagnosed between 2019 and 2022. Nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome (NS) with acute kidney injury (AKI), subnephrotic proteinuria plus AKI, isolated hematuria, and unexplained renal impairment were the six clinical syndromes for which a kidney biopsy was performed in 25 patients. Hospital admission records, progression notes, and outpatient follow up were used to collect data. Results: Acute glomerulonephritis (AGN) with nephritic syndrome (NS) affected 53% of the patients. Patients with AGN-NS were more likely to develop hypertension (48.0% vs. 15.7%) and acute renal damage (32% vs. 10%). 48% of the patients had Acute Postinfectious Glomerulonephritis. 5% of the patients had membranoproliferative glomerulonephritis. 2.5% of patients with ANCA-negative rapidly progressive glomerulonephritis had extramembranous glomerulonephritis, and 2.5% had extracapillary glomerulonephritis. The kidneys of 24 people were biopsied. The most common reason for a kidney biopsy was rapidly progressing glomerulonephritis. Conclusion: Acute postinfectious glomerulonephritis has been the most common glomerulonephritis in our study over the last three years in our Marrakech department. It manifested as a rapidly progressive glomerulonephritis in twelve of the cases.

Leukemia Infiltration Secondary Acute Renal Damage

Chronic lymphocytic leukemia is a disease that it is developed by cumulation of mature-looking small lymphocytes in blood,bone marrow,lymph nodes,spleen and other lymphatic organs and tissues.It can be attained as asymptomatic lymphocytosis in old patients;on the other hand, kidney dysfunction can also be seen as a preliminary finding. Leukemia infiltration secondary acute renal damage can rarely be seen while renal damage is being occured because of many different reasons in chronic lymphocytic leukemia patients.Here,we aimed to review the literature by presenting 70-year-old patient who was under hematology follow-up due to chronic lymphocytic leukemia,who was hospitalized in our clinic because of acute kidney damage in routine examinations and was found to have leukemic infiltration in pathology.

Clinical features of renal damage associated with Epstein-Barr virus infection in children.

To understand the renal damage and clinical features of pediatric patients with acute Epstein-Barr virus (EBV) infection. In this retrospective observational study, 548 pediatric patients who were admitted to and treated at the Xiamen Women and Children Health Center between January 2017 and December 2021 and who met the criteria of acute EBV infection were selected as participants. The sociodemographic and clinical data of these patients were collected for statistical analysis. The study population was divided into a renal damage group (41 patients) and a non-renal damage group (507 patients), and the characteristics of the two groups were compared. (1) Of the 548 enrolled patients, 340 and 208 were boys and girls, respectively. Among them, 41 patients showed renal damage (renal damage group), including 26 boys and 15 girls, and the incidence rate of renal damage was 7.48%. (2) The major renal involvements in the 41 pediatric patients with acute EBV infection in the renal damage group manifested as hematuria (56.1%), proteinuria (37.71%), hematuria + proteinuria (12.9%), edema (51.22%), hypertension (17.07%), oliguria (4.88%), and acute renal failure (2.44%). (3) The pediatric patients in the renal damage group had statistically significantly longer fever durations, higher blood EBV-DNA loads, and lower blood CD4+/CD8+ T lymphocyte ratios than those in the non-renal damage group. In pediatric patients, the incidence rate of acute EBV-induced renal damage is not low. The clinical manifestations are mostly hematuria or proteinuria, with an overall good prognosis, but occasionally severe renal damage such as acute renal failure. The possibility of secondary renal damage is high when pediatric patients with acute EBV have prolonged fever, high blood EBV-DNA loads, and decreased blood CD4+/CD8+ ratios.

The use of the drug Elizaria – a biosimilar of the original eculizumab in atypical hemolytic-uremic syndrome due to mutation of the С3 gene in children: clinical observation and literature review

This article presents the features of atypical haemolytic-uremic syndrome (ORPHA 544472) in children. Atypical haemolytic-uremic syndrome (aHUS) is defined by a triad: haemolytic anaemia, thrombocytopenia and acute kidney injury in pediatric and adult patients. The OMIM catalogue presents the phenotypic series of aHUS with mutations of the C3, CFB, CFH, CFHR1, CFHR3, DGKE, MCP, THBD genes. Atypical haemolytic-uremic syndrome is often associated with gene mutations in proteins and activators that regulate complement. We report the case of a girl who had a manifestation of aHUS at 8 years 5 months of age and a severe relapse at 8 years 10 months of age. The relapse was characterised by manifestations of haemolytic anaemia, thrombocytopenia, acute renal damage, severe arterial hypertension, high lactate dehydrogenase and membrane attack complex levels and low C3 component. After 5 courses of haemodialysis, 3 haemodiafiltration, diuresis increased and biochemical parameters improved. We presented with ASUS in a child associated with a p.Cys1101Tyr C3 gene mutation. We used a complement inhibitor, Elizaria®, a biosimilar to the original drug eculizumab, to treat a child with atypical haemolytic-uremic syndrome due to the C3 gene mutation. The complement system inhibitor therapy with Elizaria preserved the health and life of a sick girl with a severe relapse of aHUS.

Cardiac surgery-associated acute kidney injury in newborns: A meta-analysis

&lt;b&gt;Introduction&lt;/b&gt;: Acute kidney injury is a common complication following pediatric heart surgery, and it has been linked to an increased risk of morbidity and fatality.&lt;br /&gt; &lt;b&gt;Methods&lt;/b&gt;: The PubMed and Medline databases were combed for relevant research until May 2022. The terms [Cardiac surgery] AND [acute renal injury] AND [newborns OR children OR neonates] AND [randomized control studies OR randomized control trials] were used as search criteria. The studies that met the inclusion criteria were considered qualified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.&lt;br /&gt; &lt;b&gt;Results&lt;/b&gt;: A total of 2,941 newborns or children were enrolled in 14 studies, with 931 developing acute renal damage. 2,095 of the enrolled infants and children received steroid, aminophylline, dexmedetomidine, and acetaminophen therapies. In seven studies, the odds ratio for steroids was not significantly different from control. In contrast, two studies comparing aminophylline to a control group found no statistically significant change. Two studies found no significant difference in dexmedetomidine therapy compared to control. Three trials, however, found a significant difference between the acetaminophen treatment and control groups.&lt;br /&gt; &lt;b&gt;Conclusion&lt;/b&gt;: Acetaminophen was linked to a decreased risk of postoperative acute renal injury, while steroids had no benefit and aminophylline treatment could be justified.

Prevalence of chronic kidney disease among severely gas-exposed survivors in Bhopal, India.

Background The survivors of the 1984 Bhopal gas disaster frequently express concern of them being at higher risk of developing chronic kidney disease (CKD) as a consequence of the long-term health effects of gas exposure. We aimed to estimate the prevalence of CKD among the survivors of severely gas-exposed cohort assembled in 1985 after the Bhopal gas disaster to study the long-term health consequences of gas exposure. Methods We did this cross-sectional study with a sample size of 215 systematically selected participants among the severely gas-exposed survivors in Bhopal to estimate the prevalence of CKD. Sociodemographic and relevant past medical history of the participants was obtained using a semi-structured questionnaire and their blood and urine samples were collected. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Those found with reduced e-GFR and proteinuria, suggestive of CKD, were further surveyed after 3 months to differentiate CKD from acute renal damage. Results The prevalence of CKD among the severely gas-exposed cohort survivors in Bhopal was 16.7%. Multiple logistic regression analysis revealed that body mass index and level of education were significant predictors of CKD. Conclusion The prevalence of CKD among the severely exposed survivors of Bhopal was at par with the national prevalence, putting at rest the apprehension of gas-exposed survivors of being at higher risk of developing CKD.

Renoprotective effect of vinpocetine and cilostazol on glycerol induced renal injury in male rats

Acute kidney injury (AKI) is characterized by a sudden loss of kidney function that is established by increased serum creatinine levels and decreased urinary output. AKI is one of a group of functional kidney conditions&#x0D; known as acute kidney disease and disorders (AKD), which can vary in severity and self-limiting to severe and chronic. Adminstrations of glycerol generate significant elevation in serum urea and creatinine that’s mean occurance of functional abnormalities in the kidney. Vinpocetine drug has many pharmacological targets with multiple action, phosphodiesterase inhibiters-1(PDE-1) inhibitor, a voltage-gated sodium channel, and Inhibitory kinase B (IKK) are 3 main molecule targets of vinpocetine. PDE1 has been implicated in the regulation of vasoconstriction, vascular and cardiac structure remodeling, and neuro-transmission. Cilostazol, a phosphodiesterase (PDE) III inhibitors, that widely used for many cases such as reduces direct vascular injury via different mechanism, such as vasodilation and antiplatelet action, anti-inflammation and platelet-leukocyte interaction minimisation, and inhibition of vascular proliferation via up-regulation of hepatocyte growth factors. In present study, we looked at the effect and mechanism of the drugs vinpocetine and cilostazol in an animal model of glycerol-induced AKI. Experiment done during the 14-day trial, rats were divided into five groups: the control group received 2ml/kg normal saline; the induction group received 10ml/kg intramuscular glycerol injection; the vinpocetine group received 5mg/kg via gavage for 14 days and on day 7 given glycerol IM, the cilostazol group received 50mg/kg for 14 days and on day 7 given glycerol IM, and the combination group received half dose vinpocetine (2.5mg/kg) and cilostazol (25mg/kg). We discovered that the induction group had higher levels of urea and creatinine, as well as increased inflammation and oxidative stress, and that their renal tissue showed morphological changes typical of AKI, whereas the combination groups reduced glycerol induce acute renal damage. This revealed that vinpocetine and cilostazol can reinforce renal rat protection by reducing serum urea and creatinine and improving histopathological changes.

Развитие полиорганной недостаточности при синдроме длительного сдавления на фоне алкогольной интоксикации тяжелой степени (клинический случай)

We consider and analyze a clinical example of a patient with multiple organ failure in crush syndrome of the upper extremities on a hard surface by their own weight in addition to severe damage of ethanol intoxication. We consider etiology, development mechanism, symptoms, diagnosis and treatment of crush syndrome. The main manifestation is muscle breakdown, the breakdown of muscle tissue with subsequent endogenous intoxication by tissue autolysis products, pain syndrome and plasma loss, metabolic and water-electrolyte disorders, thrombosis of the microcirculatory bed. First of all, acute renal damage develops. With severe and extremely severe damage, a shock state with unstable hemodynamics is possible. In unstable hemodynamics, inotropic and vasopressor support is used. The main markers in the diagnosis are creatine phosphokinase, miglobin, an increase in creatinine and urea in the blood serum. Treatment includes intensive therapy in addition to renal replacement therapy – plasmapheresis, hemodialysis, hemodiafiltration. Narcotic analgesics are used to eliminate the pain syndrome. According to the indications, surgical treatment is carried out from necrectomy and fasciotomy to limb amputation. Mortality in crush syndrome reaches from 30 to 70 %. A favorable outcome is possible after a month.

Remdesivir May Be Associated with Acute Kidney Injury in Covid-10 Patients: A Cohort Study

Objective: To assess the outcomes of coronavirus disease-2019 patients with acute renal damage who received remdesivir against placebo at a private hospital in Karachi, Pakistan. Methodology: At the COVID-19 ICU of Hussain Lakhni Hospital, a cohort study was conducted from July 2021 to February 2022. Male and female study participants with COVID-19 and acute renal injury ranged in age from 40 to 80. Remdesivir-treated individuals with COVID-19 acute kidney injury were exposed, but placebo-treated patients with COVID-19 acute kidney injury were not exposed. In-hospital mortality, elevated serum creatinine levels, and prolonged hospital stays were the results. The data was analyzed using SPSS version 23. Results: Patients who took remdesivir had a lower mortality rate than those who were placebo (32.2% vs 67.8%, OR=0.38, 95 percent CI=0.27-0.52), with a p-value of 0.001. Remdesivir was also associated with a shorter hospital stay (4.2% versus 95.8%, OR=0.005, 95 percent CI=.003-0.009) with a p-value of 0.001). However, increased serum creatinine revealed statistically insignificant differences between groups. The odds of in-hospital mortality were 0.376 times lower (AOR=0.376, 95 percent CI=0.275-0.514, p=0.0001) and the odds of a prolonged hospital stay were 0.030 times lower (AOR=0.030, 95 percent CI=0.012-0.074, p=0.001) in the remdesivir group than in the placebo group after controlling for covariates. Practical implication: In literature Remdesvir was associated with acute kidney injury (rise in serum creatinine ) and in many centres ,it was not used in patients with acute kidney injury although it has very beneficial effect in patients of severe covid pneumonia,many centres were not using it in patients of acute renal failure. in our study , rise in serum creatinine was not significant in remdesvir group in patient with acute kidney injury ,so remdesvir must not be withheld in this group of patients as it can decrease the severity of covid pneumonia and saves patients lives Conclusion: Remdesivir is an effective medicine in COVID-19 patients with acute renal damage in terms of in-hospital mortality and duration of stay. Keywords: Acute kidney injury, coronavirus, COVID-19, in-hospital mortality, kidney damage, remdesivir, renal function, serum creatinine

Glimepiride ameliorates renal toxicity induced by cadmium in mice: Modulation of Jun N terminal kinase (JNK)/nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinases (PI3K)/protein kinase (AKT) pathways

AimsNephrotoxicity is one of the most serious health consequences of cadmium (Cd) toxic exposure. Cd was associated with nephrotoxicity through different mechanisms including apoptosis, inflammation, and oxidative stress. This study investigated the effects of glimepiride on renal inflammatory reactions and oxidative stress in response to Cd in mice animal model, pointing to the possible role of JNK/NF-кB and PI3K/AKT signaling. Materials and methodsFour groups of animals were created; the control group, the glimepiride group (4 mg/kg; i.p.), CdCl2 nephrotoxic group (6.5 mg/kg; i.p.), and the CdCl2/glimepiride group. On the other hand, molecular docking studies were used to investigate the affinity of glimepiride towards JNK, AKT, and PI3K targets. Key findingsThe CdCl2 group's serum creatinine and urea levels were found to have a significant increase when compared to the normal group. High expression of 8-OHDG, JNK, AKT, and NGAL was also detected in the CdCl2 group. In addition, coagulative necrosis of the renal tubules and increased immunostaining of NF-κB and PI3K. Furthermore, glimepiride significantly decreased the serum creatinine and urea level and alleviated the degenerative and necrotic changes within the renal tubules. Moreover, the renal NGAL and JNK were suppressed, and oxidants/antioxidants hemostasis was observed. SignificanceThe available data show that glimepiride is an attractive strategy for improving the nephrotoxicity associated with CdCl2 through inhibition of JNK/NF-κB, PI3K/AKT inflammatory pathways. From the abovementioned results, glimepiride treatment might be a potential therapeutic approach to treat renal tissue against severe acute renal damage induced by the toxic effects of CdCl2.