Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

Clinical characteristics and treatment compounds of obesity-related kidney injury

Disorders in energy homeostasis can lead to various metabolic diseases,particularly obesity.The obesity epidemic has led to an increased incidence of obesityrelated nephropathy(ORN),a distinct entity characterized by proteinuria,glomerulomegaly,progressive glomerulosclerosis,and renal function decline.Obesity and its associated renal damage are common in clinical practice,and their incidence is increasing and attracting great attention.There is a great need to identify safe and effective therapeutic modalities,and therapeutics using chemical compounds and natural products are receiving increasing attention.However,the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN.In this review,we summarize the important clinical features and compound treatment strategies for obesity and obesityinduced kidney injury.We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation,oxidative stress,insulin resistance,fibrosis,kidney lipid accumulation,and dysregulated autophagy.In addition,detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized.The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases,fostering the anticipation of novel insights in this domain.

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.

Revaccination after Acute Kidney Injury Associated with Prior COVID-19 Vaccination: Case Report

Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In situations where a new virulent strain of virus emerges or in patients at risk of severe complication from infection, it may be reasonable to consider revaccination following appropriate counselling with close monitoring of renal function.

Study of the OPG/RANKL/RANK signaling pathway in mice treated with sepsis-related acute kidney injury

Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.

Contribution of gut microbiota to drug-induced liver injury

Drug-induced liver injury(DILI)is caused by various drugs with complex pathogenesis,and diverse clinical and pathological phenotypes.Drugs damage the liver directly through drug hepatotoxicity,or indirectly through drug-mediated oxidative stress,immune injury and inflammatory insult,which eventually lead to hepatocyte necrosis.Recent studies have found that the composition,relative content and distribution of gut microbiota in patients and animal models of DILI have changed significantly.It has been confirmed that gut microbial dysbiosis brings about intestinal barrier destruction and microorganisms translocation,and the alteration of microbial metabolites may cause or aggravate DILI.In addition,antibiotics,probiotics,and fecal microbiota transplantation are all emerging as prospective therapeutic methods for DILI by regulating the gut microbiota.In this review,we discussed how the altered gut microbiota participates in DILI.

Sequential experimental observation on the curative effect of Yingbupu decoction of Zhuang medicine on stage I and II acute kidney injury

Objective:To observe the clinical efficacy of the Zhuang medicine Yingbupu decoction on stage I and II acute kidney injury through sequential test.Methods:The open one-way qualitative response sequential design of experiments was adopted,and the patients with AKI in phase I and II who met the inclusion criteria were divided into the treatment group and the control group according to the order of hospitalization by random number table.On the basis of basic treatment,the treatment group was treated with Zhuang medicine Yingbupu decoction,and the control group was treated with Jinshuibao tablet.The clinical efficacy,TCM syndrome score,24 h urine volume,serum creatinine(Scr),microalbumin in urine(mAlb),neutrophil Gelatinase related lipid delivery albumin(NGAL)of the two groups were compared,and the adverse reactions and complications of the two groups were observed.Results:After 14 d of treatment,when the treatment group reached the 10th case,the experimental line contacted the upper bound U-line and reached the experimental standard to terminate the experiment.The effective hypothesis was accepted,and it was believed that the Zhuang medicine Yingbupu decoction had a therapeutic effect on stage I and II AKI.The conclusion was drawn that the treatment group received the Zhuang medicine Yingbupu.The clinical effective rate and improvement days were similar between the two groups,and there was no significant difference(P>0.05).However,the integral value of traditional Chinese medicine syndrome in the treatment group was lower than that in the control group(P<0.05),After treatment,the Scr,mAlb,and NGAL levels of patients in both groups were lower than before treatment(P<0.05).After treatment,the Scr,mAlb,and NGAL values in the treatment group were significantly lower than those in the control group(P<0.05).After treatment,the 24-hour urine volume in both groups was higher than that before treatment,and the values in the treatment group were significantly higher than those in the control group(P<0.05).During the treatment period,there were no significant adverse reactions or complications in either group.Conclusion:The Zhuang medicine Yingbupu decoction is effective in treating stage I and II AKI,and the Zhuang medicine Yingbupu can significantly improve the symptoms and quality of life of patients with stage I and II AKI.Its improvement of renal function is better than that of Jinshuibao tablets,and its safety is good.

Predictors of Fatal Outcome in Hospitalised Adult Patients with Acute Kidney Injury at Two Tertiary Hospitals in Sub-Saharan Africa

Introduction: Data on mortality in acute kidney injury (AKI) derives from high-income countries where AKI is hospital-acquired and occurs in elderly patients with a high burden of cardiovascular disease. In sub-Saharan Africa (SSA), AKI is community-acquired occurring in healthy young adults. We aimed to identify predictors of fatal outcomes in patients with AKI in two tertiary hospitals in Cameroon. Methods: Medical records of adults with confirmed AKI, from January 2018 to March 2020 were retrieved. The outcomes of interest were in-hospital deaths and presumed causes of death. We used multiple logistic regressions modeling to identify predictors of death. The study was approved by the ethics boards of both hospitals. Values were considered significant for a p-value of 0.05. Results: We included 285 patient records (37.2% females). The mean (SD) age was 50.1 (19.0) years. Hypertension (n = 97, 34.0%), organ failure (n = 88, 30.9%), and diabetes (n = 60, 21.1%) were the main comorbidities. The majority of patients had community-acquired AKI (78.6%, n = 224), were KDIGO stage 3 (88.8%, n = 253), and needed dialysis (52.6%, n = 150). Up to 16.7% (n = 25) did not receive what was needed. The in-hospital mortality rate was 29.1% (n = 83). Lack of access to dialysis (OR = 27.8;CI: 5.2 - 149.3, p = 0.001), hypotension (OR = 11.8;CI: 1.3 - 24.8;p = 0.001) and ICU admission (OR = 5.7;CI: 1.3 - 24.8, p = 0.001) were predictors of mortality. The presence of co-morbidities or underlying diseases (n = 46, 55%) were the main causes of death. Conclusions: In-hospital AKI mortality is high, as in other low- and middle-income economies. Lack of access to dialysis and the severity of the underlying illness are major predictors of death.

Sound waves and solutions:Point-of-care ultrasonography for acute kidney injury in cirrhosis

This article delves into the intricate challenges of acute kidney injury(AKI)in cirrhosis,a condition fraught with high morbidity and mortality.The complexities arise from distinguishing between various causes of AKI,particularly hemodynamic AKI,in cirrhotic patients,who experience hemodynamic changes due to portal hypertension.The term"hepatocardiorenal syndrome"is introduced to encapsulate the intricate interplay among the liver,heart,and kidneys.The narrative emphasizes the often-overlooked aspect of cardiac function in AKI assessments in cirrhosis,unveiling the prevalence of cirrhotic cardiomyopathy marked by impaired diastolic function.The conventional empiric approach involving volume expansion and vasopressors for hepatorenal syndrome is critically analyzed,highlighting potential risks and variable patient responses.We advocate for a nuanced algorithm for AKI evaluation in cirrhosis,prominently featuring point-of-care ultrasonography(POCUS).POCUS applications encompass assessing fluid tolerance,detecting venous congestion,and evaluating cardiac function.

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.

Clinical Presentation and Treatment Outcomes of Pregnancy-Related Acute Kidney Injury among Pregnant Women Admitted at the Benjamin Mkapa Hospital in Tanzania

Background: Globally, PRAKI is among the leading causes of death in pregnant women. The prevalence, causes and outcome of this condition vary among countries due to differences in environmental, socioeconomic, and health delivery systems. The common causes that have been reported in several studies are PIH, Haemorrhages and Sepsis while the outcomes may be either complete renal recovery, progression to CKD and hence dialysis dependency or death. This study aimed at determining clinical presentation and treatment outcomes of Pregnancy-Related Acute Kidney Injury in Pregnant women admitted at the Benjamin Mkapa Hospital, Dodoma, Tanzania. Results: Out of 4007 pregnant women who were admitted to the maternity ward 51 pregnant women were found to have PRAKI. Of those with PRAKI, 74.5% were between 21 to 25 years. The leading causes of PRAKI were PPH 12 (23.53%), Eclampsia 12 (23.53%), and pre-eclampsia 12 (23.5%). Hemodialysis therapy was provided to 22 (43.1%) patients, 15 (29.4%) individuals recovered spontaneously with medical management and 14 (27.5%) missed haemodialysis therapy due to various reasons. The mortality due to PRAKI was 17 (33.3%). Conclusion and Recommendation: Pre-eclampsia/eclampsia and post-partum haemorrhage were found to be the main causes of PRAKI. The mortality related to PRAKI is high and Hemodialysis therapy is vital help to prevent deaths for pregnant women with PRAKI. Pregnant women who develop acute kidney injury should be followed closely and a nephrologist should be consulted early. Early referral should be done by the lower level facilities for all at-risk pregnant women to a specialized multidisciplinary health facility.

Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute Kidney Injury: A Case Report

Spontaneous Tumor Lysis Syndrome (STLS) is a rare oncologic condition caused by the breakdown of neoplastic tissue in the absence of traditional anti-tumor therapy. It is postulated that cancers with rapidly dividing cells lead to increased cell turnover which exceeds the kidneys’ ability to adequately filtrate by-products of cellular breakdown (i.e., phosphate, potassium, anduric acid), leading to end organ damage. It has been reported in the past that kidney failure is a sequelae of Tumor Lysis Syndrome (TLS), but there have been no reports that demonstrate acute kidney injury (AKI) preceding TLS. The case presented here demonstrates TLS in a patient with no formal cancer diagnosis, who had received no chemotherapy or radiation that was precipitated by an iatrogenic AKI with chlorthalidone and ibuprofen. This unusual pattern of AKI preceding STLS may provide insight into the pathophysiology of the condition and could possibly lead to greater understanding of this phenomenon.

Exertional Rhabdomyolysis Induced Acute Kidney Injury: A Case Report and Literature Review

Background: The exRML (exertional rhabdomyolysis) is a pathophysiologic condition of skeletal muscle cell damage and breakdown associated with high intensity or prolonged exercise, normal exercise under extreme circumstances, or sudden and excessive skeletal muscle contraction. It may manifest from the increase in CK (creatine kinase) or MYO (myoglobin), a protein that can cause life-threatening injury to the kidney (AKI, acute kidney injury), and may or may not be associated with myoglobinuria. Here, we presented a case of exRML with AKI, and then reviewed the related reports. Vigorous hydration, sodium bicarbonate and furosemide are key treatments. Aim: To examine an elderly patient with exRML induced AKI and the key treatment process. Case summary: A 61-year-old man left our hospital without permission after his admission and has been walking for almost 30 kms with no water and food intake, then was diagnosed exRML and exRML induced AKI with an obvious elevation of CK, MYO and decrease of eGFR (estimated glomerular filtration rate) after coming back, and was treated with vigorous hydration, loop diuresis, sodium bicarbonate, prostaglandin and Shenkang injection. After vigorous resuscitation, the patient’s renal function, CK and MYO returned normal. Conclusions: The exRML can cause serious complications such as AKI and death. Delayed diagnosis can be critical;therefore, manner of time should be taken to achieve a favorable prognosis.

A Case of Waldenström Macroglobulinemia with Acute Kidney Injury as the First Manifestation and Literature Review

Waldenström macroglobulinemia is a rare lymphoid tumor accounting for 2% of all hematological malignancies. Renal complications are less common compared to multiple myeloma, with the most frequent renal manifestations being microproteinuria and microhematuria. This paper presents a case of Waldenström macroglobulinemia with acute kidney injury as the initial manifestation. A 75-year-old male was admitted to the Affiliated Hospital of Hebei University after elevated blood creatinine levels were detected for one day. Upon admission, his blood creatinine was 255 μmol/L, urine protein was 1+, urine erythrocytes were negative, electrophoresis showed IgM positivity in the κ-region, and a bone marrow biopsy indicated a tendency towards lymphoplasmacytic lymphoma. The patient was discharged after receiving a treatment regimen of prednisone acetate, thalidomide, and cyclophosphamide, and continued oral medication outside the hospital. The patient returned two weeks later due to diarrhea and was found to have a blood creatinine level of 985 μmol/L, along with severe acidosis and hyperkalemia. The patient refused renal replacement therapy and was not followed up, resulting in a poor prognosis. Additionally, a review of the literature is provided to contextualize this case within the broader scope of existing research.

COVID-19-related liver injury:Focus on genetic and drug-induced perspectives

BACKGROUND Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is considered as one of the major etiopathogenetic factors for liver injury.Recent evidence has shown that an underlying genetic factor may also occur.Hence,it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.AIM To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019(COVID-19)-related liver injury.METHODS Reference Citation Analysis,PubMed,Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration,site and type of study,sample size with any subgroups and drug-induced liver injury outcome.Genetic aspects were extracted from the most current pertinent publications.RESULTS In all studies,the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease,hospital stay,number of COVID-19 treatment drugs and worse clinical outcomes.In addition,membrane bound O-acyltransferase domain containing 7 rs641738,rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients.CONCLUSION Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a geneticpropensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients shouldbe done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration.Additional molecular and translational research is warranted in this regard.

Dissecting the molecular pathophysiology of drug-induced liver injury

Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways.

Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

AIM To summarize and compare the clinical characteristics of drug-induced liver injury(DILI) and primary biliary cirrhosis(PBC).METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data(sex and age),biochemical indexes(total protein,albumin,alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,indirect bilirubin,alkaline phosphatase,and gamma glutamyltransferase),immunological indexes [immunoglobulin(Ig) A,Ig G,Ig M,antinuclear antibody,anti-smooth muscle antibody,anti-mitochondrial antibody,and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients,untyped DILI patients and patients with different types of DILI(hepatocellular type,cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes(except ALB),immunological indexes,positive rates of autoantibodies(except SMA),and number of cases of patients with different ANA titers(except the group at a titer of 1:10000)significantly differed between DILI patients and PBC patients. Biochemical indexes,immunological indexes,and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes(n = 30),inflammatory cell infiltration around bile ducts(n = 29),and atypical hyperplasia of small bile ducts(n = 28). DILI manifested mainly as fatty degeneration of hepatocytes(n = 15) and spotty necrosis or loss of hepatocytes(n = 14).CONCLUSION Although DILI and PBC share some similar laboratory tests(biochemical and immunological indexes) and pathological findings,they also show some distinct characteristics,which are helpful to the differential diagnosis of the two diseases.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.