Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.

Exploring the Role of Serum Cystatin C in Early Detection of Acute Kidney Injury among On-Pump Cardiac Surgery Patients: A Single-Center Investigation in Bangladesh

Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.

Risk Factors for Acute Kidney Injury in Patients Receiving Antibiotic Therapy:A Systematic Review and Meta-Analysis

[Objectives]To systematically analyze the risk factors for acute kidney injury(AKI)in patients treated with antibiotics and to conduct a meta-analysis of published clinical studies.[Methods]PubMed,Web of Science,and Embase were searched for relevant cohort and case-control studies from January 1,2001,to October 31,2022.Meta-analysis was performed using RevMan5.4 and StataMP15.[Results]A total of 22 studies were included.Regarding patient factors,serum creatinine(SCr;MD=1.03,95%CI of-0.07 to-0.02)was associated with increased antibiotic-associated AKI.Regarding the comorbidities and clinical factors,diabetes(OR=1.34,95%CI of 1.06 to 1.69,tumor(OR=2.07,95%CI of 1.13 to 3.79),pneumonia(OR=1.83,95%CI of 1.24 to 2.71),mechanical ventilation(OR=3.44,95%CI of 1.93 to 6.12),and ICU admission(OR=2.83,95%CI of 2.13 to 3.75)increased the risk of AKI in patients receiving antibiotic therapy.Regarding drug factors,diuretics(OR=2.76,95%CI of 2.16 to 3.52)increased the risk of antibiotic-associated AKI.[Conclusions]This paper may assist clinicians in predicting the risk factors for AKI in patients receiving antibiotic therapy.

Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary tract.It is regarded as one of the most prevalent causes of acute kidney injury(AKI),accounting for 5%–10%of cases.Acute severe obstruction of the urinary tract is a potentially threatening situation for the kidneys and therefore requires prompt identification and management to relieve obstruction.The aim of the present article is to review and synthesize available evidence on obstructive uropathy,providing a clinical guideline for clinicians.A literature review on obstructive uropathy in the context of AKI was performed,focusing on the least clarified aspects regarding diagnosis and management.Recent literature searching was conducted in English and top-level evidence articles including systematic reviews,metanalyses and large series were prioritized.Acute obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the kidney.Early recognition of the leading cause and its exact location is essential to ensure prompt urinary drainage together with the most suitable drainage technique selection.A multidisciplinary approach,including urologists,nephrologists,and other medical specialties,is best suited to correctly manage concomitant hemodynamic changes,fluid and electrolyte imbalances,and other related issues.Obstructive uropathy is one of the leading causes of AKI.Recognition of patients suitable for early diversion and feasibility or adequate selection of the indicated technique is sometimes challeng-ing.A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management.

Eff ects of continuous renal replacement therapy on infl ammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury

BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

The Role for AVE0991 (MAS-Receptor Angiotensin II (1-7) Agonist) in Reducing Cisplatin-Induced Acute Kidney Injury on C57BL/6 Mice

Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.

Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury

BACKGROUND:To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor(MANF) in regulating sepsis-associated acute kidney injury(S-AKI).METHODS:A total of 96 mice were randomly divided into the control group,control+MANF group,S-AKI group,and S-AKI+MANF group.The S-AKI model was established by injecting lipopolysaccharide(LPS) at 10 mg/kg intraperitoneally.MANF(200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups.An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups.Serum and kidney tissue samples were obtained for biochemical analysis.Western blotting was used to detect the protein expression of MANF in the kidney,and enzyme-linked immunosorbent assay(ELISA) was used to determine expression of MANF in the serum,pro-inflammatory cytokines(tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]).Serum creatinine(SCr),and blood urea nitrogen(BUN)were examined using an automatic biochemical analyzer.In addition,the kidney tissue was observed for pathological changes by hematoxylin-eosin staining.The comparison between two groups was performed by unpaired Student’s t-test,and statistics among multiple groups were carried out using Tukey’s post hoc test following one-way analysis of variance(ANOVA).A P-value <0.05 was considered statistically significant.RESULTS:At the early stage of S-AKI,MANF in the kidney tissue was up-regulated,but with the development of the disease,it was down-regulated.Renal function was worsened in the S-AKI group,and TNF-α and IL-6 were elevated.The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney.The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group.CONCLUSION:MANF treatment may significantly alleviate renal injury,reduce the inflammatory response,and alleviate or reverse kidney tissue damage.MANF may have a protective effect on S-AKI,suggesting a potential treatment for S-AKI.

Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery:A prospective observational study

BACKGROUND Patients admitted to intensive care unit(ICU) after cardiac surgery develop acute kidney injury(AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome.AIM To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome.METHODS This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome.Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development.RESULTS After ICU admission, 55 patients(26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore Ⅱ(OR: 1.18;95%CI: 1.06-1.31, P = 0.003), white blood cells(WBC) pre-operatively(OR: 1.0;95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease(OR: 2.82;95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113(777–2195) vs 714(511–1020) min, P = 0.0001] and ICU length of stay [70(28–129) vs 26(21–51) h, P = 0.0001], higher rate of ICU-acquired weakness(16.4% vs 5.3%, P =0.015), reintubation(10.9% vs 1.3%, P = 0.005), dialysis(7% vs 0%, P = 0.005), delirium(36.4% vs 23.8%, P = 0.001) and mortality(3.6% vs 0.7%, P = 0.046).CONCLUSION Patients present frequently with AKI after cardiac surgery. EuroScore Ⅱ, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic

BACKGROUND There are two known types of exercise-induced acute renal failure.One is the long-known myoglobinuria-induced acute renal failure due to severe rhabdomyolysis,and the other is the recently recognized non-myoglobinuria-induced acute renal failure with mild rhabdomyolysis.Exercise-induced acute renal failure was first reported in 1982.Non-myoglobinuria-induced acute renal failure is associated with severe low back pain and patchy renal vasoconstriction,and it is termed post-exercise acute renal failure because it usually occurs hours after exercise.It is also called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise(ALPE).AIM To makes a significant contribution to medical literature as it presents a study that investigated a not-widely-known type of exercise-induced acute renal failure known as ALPE.METHODS We performed a database search selecting papers published in the English or Japanese language.A database search was lastly accessed on September 1,2022.The results of this study were compared with those reported in other case series.RESULTS The study evaluated renal hypouricemia as a key risk factor of ALPE.The development of ALPE is due to the sum of risk factors such as exercise,hypouricemia,nonsteroidal anti-inflammatory drugs,vasopressors,and dehydration.CONCLUSION In conclusion,hypouricemia plays a key role in the development of ALPE and is often associated with anaerobic exercise.The development of ALPE is a result of the cumulative effects of risk factors such as exercise,hypouricemia,NSAIDs,vasopressors,and dehydration.

Protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats

Objective:To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.Methods:A total of 60 Wister rats were included in the study and divided into control group(n = 10),model group(n = 25) and treatment group(n = 25).Model group and treatment group received intraperitoneal injection of endotoxin(ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL.Five rats were taken out of model group and treatment group respectively at 1 h(T1),6 h(T2),12 h(T3),24 h(T4) and 48 h(T5),for intraperitoneal injection of ET 30 mg/kg.Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET.For three groups,5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points.Concentrations of serum tumor necrosis factor and ET-1 were determined by using ELISA.The renal pathologic changes were observed under the microscope.Results:Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5(P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5(P < 0.05).At T2-T5,blood urea nitrogen levels in model group and treatment group were significantly higher than control group(P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5(P < 0.05).Concentrations of serum tumor necrosis factor in model group and treatment group were significantly higher than control group at T1-T5(P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5(P < 0.05).Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5(P <0.05) while the levels in treatment group at T1-T4 were significantly lower man model group(P <0.05).Rats in control group showed no swelling or hyperaemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells.Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition,hyperaemia and angiectasis in glomerulus,degenerative opacities and vacuolar degeneration,and maximized injury were observed at T4.Injury in renal tissue in treatment group was significantly milder than model group.Conclusions:Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.

Acute renal injury after partial hepatectomy

Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury(AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs.

Caspase-1 inhibition alleviates acute renal injury in rats with severe acute pancreatitis

AIM:To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis(SAP).METHODS:Forty-two Sprague-Dawley rats were randomly divided into three groups:healthy controls(HC,n=6),SAP rats treated with saline(SAP-S,n=18),or SAP rats treated with a caspase-1/interleukin(IL)-1β-converting-enzyme(ICE)inhibitor(SAP-I-ICE,n=18).SAP was induced by retrograde infusion of 5%sodium taurocholate into the bile-pancreatic duct.HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate.Rats received an intraperitoneal injection of isotonic saline(SAP-S)or the inhibitor(SAP-ICE-I)at 2 and 12 h after induction of acute pancreatitis.Surviving rats were sacrificed at different time points after SAP induction;all samples were obtained and stored for subsequent analyses.The levels of blood urea nitrogen(BUN)and creatinine(Cr)were measured using automatic methods,and serum IL-1βconcentrations were measured by an enzymelinked immunosorbent assay.Intrarenal expression of IL-1β,IL-18 and caspase-1 mRNAs was detected by RT-PCR.IL-1βprotein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining,respectively.RESULTS:The serum levels of BUN and Cr in the SAP-S group were 12.48±2.30 mmol/L and 82.83±13.89μmol/L at 6 h,23.53±2.58 mmol/L and 123.67±17.67μmol/L at 12 h,and 23.60±3.33 mmol/L and125.33±21.09μmol/L at 18 h,respectively.All were significantly increased compared to HC rats(P<0.01for all).Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h(P<0.01 for all).Serum IL-1βlevels in the SAP-S group were 276.77±44.92 pg/mL at 6 h,308.99±34.95pg/mL at 12 h,and 311.60±46.51 pg/mL at 18 h;all significantly higher than those in the HC and SAP-ICE-I groups(P<0.01 for all).Intrarenal expression of IL-1βmRNA was weak in HC rats,but increased significantly in SAP-S rats(P<0.01).ICE inhibition significantly decreased the expression of IL-1βand IL-18 mRNAs(P<0.05 for all vs SAP-S),whereas caspase-1 mRNA expression was not significantly different.Weak IL-1βimmunostaining was observed in HC animals,and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells.IL-1βimmunostaining was significantly descended in SAP-ICE-I rats compared to SAP-S rats(P<0.05).Caspase-1 inhibition had no effect on the severity of kidney tissue destruction.CONCLUSION:The expression of caspase-1-activated cytokines IL-1βand IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP.Caspase-1inhibition improves renal function effectively.

Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP). METHODS: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-α, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation. RESULTS: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P < 0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P < 0.01, 29.200 ± 5.710 μmol/L vs 38.400 ± 11.344 μmol/L; P < 0.05, 33.533 ± 10.106 μmol/L vs 45.154 ± 17.435 μmol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P < 0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P < 0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P < 0.05, 57.50 (22.50) and 52.50 (15.00) μmol/L vs 65.00 (7.50) μmol/L; P < 0.01, 57.50 (27.50) and 45.00 (12.50) μmol/L vs 74.10 (26.15) μmol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-α (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P < 0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91 ± 20.61 and 66.86 ± 22.10 U/mL, 63.13 ± 26.31 and 53.63 ± 12.28 U/mL vs 101.46 ± 14.67 and 105.33 ± 18.10 U/mL, respectively]. CONCLUSION: Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.

Effects of prostaglandin E combined with continuous renal replacement therapy on septic acute kidney injury

BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.

Optimal indicator for changing the filter during the continuous renal replacement therapy in intensive care unit patients with acute kidney injury:A crossover randomized trial

BACKGROUND:The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy(CRRT)in intensive care unit(ICU)patients with acute kidney injury(AKI).METHODS:Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial,i.e.,groups A and B.Patients in the group A were firstly treated with continuous veno-venous hemofiltration(CVVH),followed by continuous veno-venous hemodiafiltration(CVVHDF).Patients in the group B were firstly treated with CVVHDF followed by CVVH.Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared.A correlation analysis between the delivered dose and pre-filter pressure(P_(PRE))and transmembrane pressure(P_(TM))was performed.Receiver operating characteristic(ROC)curves were constructed to evaluate the accuracy of P_(TM) as an indicator for filter replacement.RESULTS:A total of 50 cases were analyzed,27 in the group A and 23 in the group B.Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities,compared with those at the initiation of treatment(all P<0.05).In the late stage of CRRT,the possible rebound of serum medium-molecular-weight solute concentration was observed.P_(TM) was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities.The threshold for predicting the rebound of serum concentration of medium-molecularweight solute by P_(TM) was 146.5 mm Hg(1 mm Hg=0.133 k Pa).CONCLUSIONS:The filter can be used as long as possible within the manufacturer’s safe use time limits to remove small-molecular-weight solutes.P_(TM) of 146.5 mm Hg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.

Changing picture of renal cortical necrosis in acute kidney injury in developing country

Renal cortical necrosis(RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome(HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury(AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications(septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main(60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients.

Profile of Patients with Acute Renal Injury in N’Djamena: About 36 Cases

Introduction: The incidence of acute renal injury (AKI) has increased in recent decades. Acute renal failure is defined by the abrupt arrest (within hours or days) of the kidney excretory function. Oliguria (urine output 24h) is presented in about half of the cases. The circumstances of the occurrence of AKI are multiple: surgical, traumatic, obstetric, medical, often obvious. Its prognosis depends on the speed of management and the associated organ failure. The objective of this study is to describe the profile of patients in emergency hemodialysis at the Nephrology Unit of the National Reference General Hospital (HGRN) in N’Djamena, Chad. Methods: This was a multicenter, descriptive study in patients with acute renal failure place over a period of 12 months in the emergency departments of the 2 hospitals in N’Djamena. Defined as carriers of an AKI (RIFLE criteria), patients with: 1) Oliguria: urinary output 400 ml/24h (<0.5 ml/kg/h in children) or anuria: urinary output 300 ml/24h;2) Associated with an increase in serum creatinine: serum creatinine × 3 or serum creatinine> 350 μmol/l or decrease of GFR by 75%. Results: Of the 311 patients admitted, 36 cases met the inclusion criteria, a frequency of 11.57%. The mean age was 34.46 years with extremes ranging from 7 to 80 years. The female sex predominated with 52.80% as sex ratio of 0.91. Isolated hypertension was noted with 38.88%. Dyspnea accounted for 41.66% of patients admitted to emergency departments. In our series, 50% of our patients had hyperthermia at admission. Oliguria was observed in 41.70% of the cases. Edema accounted for 33.33% of cases. The AKI with the “failure” criterion was 58.34% (21/36), with the criterion “injury” 25% (9 cases) and the criterion “risk” 16.66 (6 cases). AKI were organic in 83.34% (30/36). It was noted that 14 patients, 38.8% had an infectious syndrome. There were 6 patients who had (16.66%) an obstructive AKI, 5 patients (13.88%) had eclampsia, 4 patients (11.12%) had hepatocellular insufficiency, 3 patients (8.34% Cardiac, 2 patients (5.56%) extracellular dehydration and 2 patients (5.56%) whose cause is indeterminate. It was noted that 10 patients, as 27.7%, had fully recovered their renal function after vascular filling and etiological treatment. Four (4) patients with obstructive obstruction were referred to the urology department. There were 22 patients who had benefited from the hemodialysis. 6 patients recovered completely their renal function. We had recorded a number of deaths in our study which was 44.44% (16/36). Septic shock was the most frequent cause of death in 50% of cases. Conclusion: The incidence of AKI in our study was 11.57%. It affects a young population and despite the therapeutic progress, the mortality remains high. The causes are multiple, entangled, dominated by infectious syndrome and hypovolemia. Prevention seems to be the best therapeutic option to avoid the installation or worsening of an AKI.

Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis. MethodsA model for bilateral post ischemic renal injury in rats was developed by clamping renal pedicles for 45 min. Renal tissular DNA fragmentation analysis and renal tissular HE staining were used. Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT mediated dUTP nick and labeling (TUNEL). ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury. Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries. ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

Efficacy of Ulinastatin Combined with Continuous Renal Replacement Therapy in the Treatment of Sepsis Acute Kidney Injury and Its Effects on Systemic Inflammation, Immune Function and miRAN Expression

Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.

Advances in oxidative stress and NOD-like/toll-like receptors in acute renal injury

Acute Kidney Injury(AKI)is a clinical syndrome characterized by rapid renal deterioration with high morbidity and mortality.Renal reperfusion(IRI),renal toxicity and sepsis are the main causes of AKI.IRI is one of the main causes of acute kidney injury in clinic,accounting for 75%of all the causes of AKI[1].The fatality rate of AKI caused by IRI is high,and the surviving patients may leave chronic renal impairment with different degrees[2].A number of studies have shown that ischemia-reperfusion injury leading to renal dysfunction is directly related to oxidative stress,and the inhibition of oxidative stress through nod-like/toll-like signaling pathway can reduce acute renal injury.This review summarizes the research progress in regulating oxidative stress and the relationship between innate immune receptors and acute renal injury.