Acute Failure Research Articles

Open versus mini-invasive partial and radical nephrectomy complications: results from the French national health database

BackgroundLaparoscopic surgery is associated with a lower morbidity than open surgery. No recent data compared kidney cancer surgery in the French population using the National Health Insurance database (PMSI-MCO).AimsWe explore and compare the surgical morbidity rates between laparoscopic and open laparotomy for kidney cancer.MethodsThe initial length of stay and complications parameters during the three postoperative months were described for renal cancer in every French center in 2018. We compared Relative Risks (RR [95% CI]) between laparoscopic and open surgery for both radical and partial nephrectomy.ResultsAmong 8,162 patients, 3,525 had a radical nephrectomy, 978 open, 2,547 laparoscopic surgeries; 4,637 patients had partial nephrectomies, 1,778 open 2,859 laparoscopic surgeries. For radical surgery, the most common complications were urinary infections (7.8%), acute renal failure (8.9%), sepsis (8.4%), bleeding (9.3%), and postoperative anemia (5.9%); the RR for laparoscopic versus open surgery were respectively 0.68 [0.54;0.86], 0.71 [0.57;0.88], 0.69 [0.55;0.86], 0.83 [0.66;1.03], 0.56 [0.43;0.73]. For partial nephrectomies, the most common complications were urinary infections (7.7%), bleeding (11.6%), and postoperative anemia (5.8%), with RR of 0.71 [0.58;0.87], 0.61 [0.52;0.71], and 0.64 [0.51;0.81]. The mean length of stay was 7.7 for open radical nephrectomy, 6.3 for laparoscopic radical nephrectomy, 7.5 for open partial nephrectomy, and 5 for laparoscopic partial nephrectomy.ConclusionsThe laparoscopic approach had fewer postoperative complications and a shorter length of stay than open surgery for partial and radical nephrectomy. The PMSI analysis provided an exhaustive description of surgical practice for kidney cancer and surgical complications in France.Clinical trial numberNot applicable.

ACEIs in high blood pressure: friend or enemy?

Optimal blood pressure control has been one of the fundamental objectives of primary care physicians and other medical specialties for many years. ACEIs (angiotensin-converting enzyme inhibitors) are one of the families of medications with an antihypertensive effect with the greatest experience in their use over decades. A 70-year-old patient previously diagnosed with high blood pressure and treated with ACEI, began in January 2013 with progressive worsening of kidney function.There are several mechanisms by which ACEIs produce an AKF (Acute Kidney Failure), such as efferent arteriolar vasodilatation because of blocking Angiotensin 2 effect or inmunoallergic mechanisms, or even different pathologies that could trigger it (congestive heart failure, liver cirrhosis with ascites and in presence of bilateral renal stenosis or unilateral stenosis of a single functioning kidney). The use of ACEIs as a first-line treatment for high blood pressure is supported by diverse clinical guidelines and by excellent results in a broad profile of patients. In a small percentage of cases, they have shown adverse effects that can affect the functioning of several systems involved in the correct control of the patient's cardiovascular risk, such as the renal system.

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Incidence and risk factors of postoperative delirium in lumbar spinal fusion patients: A National Database analysis

Postoperative delirium (POD) is a frequent complication observed in patients following spinal surgeries. The incidence of POD is particularly concerning for major procedures like lumbar spinal fusion, leading to a range of detrimental outcomes. However, existing research on the prevalence and risk factors associated with POD after lumbar spinal fusion is limited, especially when relying on data from large-scale national databases. This study employed a comprehensive analysis of the National Inpatient Sample (NIS) database, encompassing data from 2010 to 2019. The study population included patients who underwent primary lumbar spinal fusion surgery. We compared patients who did not experience POD with those who developed POD postoperatively, analyzing demographic characteristics, pre-existing comorbidities, and perioperative complications. Analysis of the NIS database identified a total of 493,481 patients who underwent lumbar spinal fusion. The overall incidence of POD following the procedure was 1.07%. Patients who experienced delirium postoperatively exhibited significantly longer hospital stays, incurred higher healthcare costs, and faced a heightened risk of in-hospital mortality (p < 0.001). Additionally, POD following lumbar spinal fusion was associated with various medical complications, including acute renal failure, myocardial infarction, pneumonia, pulmonary embolism, stroke, and urinary tract infections. Several independent predictors were identified as being significantly associated with postoperative delirium, including advanced age (≥65 years old), pre-existing neurological disorders, a history of alcohol or drug abuse, depression, psychotic disorders, fluid and electrolyte imbalances, diabetes, weight loss, deficiency anemia, coagulopathy, congestive heart failure, pulmonary circulation disorders, peripheral vascular disease, chronic renal insufficiency, and receiving treatment at a teaching hospital. Notably, neurological disorders demonstrated the strongest correlation with the development of postoperative delirium. Overall, our analysis revealed a relatively low prevalence of POD following lumbar spinal fusion surgery. Nevertheless, it is critical to investigate and understand the independent predictors of POD to effectively prevent and mitigate its negative impact on patient outcomes.

Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease.

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.

A Rare Presentation of Herpes Simplex Virus Encephalitis With Ischemic Stroke and Associated Acyclovir-Induced Acute Kidney Injury

A Rare Presentation of Herpes Simplex Virus Encephalitis With Ischemic Stroke and Associated Acyclovir-Induced Acute Kidney Injury

Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Clinical characteristics and predictors of complications and mortality in hospitalized octogenarian patients with COVID-19: an ambispective study.

This study aimed to describe the clinical presentation of COVID-19 in hospitalized patients aged 80 or above and to identify predictors for death and complications throughout the epidemic waves of the disease. This was an observational, multicenter, ambispective study conducted between March 2020 and August 2021 using data collected in five centers from southern metropolitan area of Barcelona (COVID-MetroSud cohort). Patients were grouped based on the pandemic waves of inclusion in the registry. We conducted a descriptive analysis, followed by bivariate and multivariate analyses (binary logistic regression) to identify predictors of risk for death or complications. A total of 1192 patients (mean [SD] age 85.7 [4.22] years and 46.8% female) were included. The most frequently reported symptoms in all waves were fever (63.1%), cough (56.5%), dyspnea (48.2%), and asthenia (27.5%). Laboratory and radiological findings consistently showed abnormal bilateral chest X-ray results (72.5% of patients) and elevated inflammatory markers such as lactate dehydrogenase (mean [SD] 335 [188] U/L), C-reactive protein (CRP) (mean [SD] 110 [88.4] U/L), and ferritin (mean [SD] 842 [1561] U/L). Acute respiratory distress syndrome (43.7%), renal failure (19.2%), and delirium (17.5%) were the most frequent complications. The overall mortality rate was 41.4% and declined across the epidemic waves. Age, diabetes mellitus, heart failure, dyspnea, and higher baseline levels of creatinine were identified as risk factors for complications, while a higher Barthel index and presence of cough were found to be protective. Age, dyspnea, abnormal bilateral chest X-ray, CRP, and sodium were identified as risk factors for death. This study demonstrates the clinical presentation of COVID-19 (fever, cough, dyspnea, and asthenia) and the different risk factors for mortality and complications in octogenarian hospitalized patients throughout the pandemic. These findings could be highly valuable for managing future virus pandemics.

Bidirectional Impact of Varying Severity of Acute Kidney Injury on Calcium Oxalate Stone Formation.

Acute Kidney Injury (AKI) is a prevalent renal disorder. The occurrence of AKI may promote the formation of renal calcium oxalate stones by exerting continuous effects on renal tubular epithelial cells. We aimed to delineate the molecular interplay between AKI and nephrolithiasis. A mild (20 min) and severe (30 min) renal ischemia-reperfusion injury model was established in mice. Seven days after injury, calcium oxalate stones were induced using glyoxylate (Gly) to evaluate the impact of AKI on the formation of kidney stones. Transcriptome sequencing was performed on tubular epithelial cells (TECs) to elucidate the relationship between AKI severity and kidney stones. Key transcription factors (TF) regulating differential gene transcription levels were identified using motif analysis, and pioglitazone, ginkgetin, and fludarabine were used for targeted therapy to validate key transcription factors as potential targets for kidney stone treatment. Severe AKI led to increased deposition of calcium oxalate crystals in renal, impaired kidney function, and upregulation of kidney stone-related gene expression. In contrast, mild AKI was associated with decreased crystal deposition, preserved kidney function, and downregulation of similar gene expression. Transcriptomic analysis revealed that genes associated with inflammation and cell adhesion pathways were significantly upregulated after severe AKI, while genes related to energy metabolism pathways were significantly upregulated after mild AKI. An integrative bioinformatic analysis uncovered a TF regulatory network within TECs, pinpointing that PKNOX1 was involved in the upregulation of inflammation-related genes after severe AKI, and inhibiting PKNOX1 function with Pioglitazone could simultaneously reduce the increase of calcium oxalate crystals after severe AKI in kidney. On the other hand, motif analysis also revealed the protective role of STAT1 in the kidneys after mild AKI, enhancing the function of STAT1 with Ginkgetin could reduce kidney stone formation, while the specific inhibitor of STAT1, Fludarabine, could eliminate the therapeutic effects of mild AKI on kidney stones. Inadequate repair of tubular epithelial cells after severe AKI increases the risk of kidney stone formation, with the upregulation of inflammation-related genes regulated by PKNOX1 playing a role in this process. Inhibiting PKNOX1 function can reduce kidney stone formation. Conversely, after mild AKI, effective cell repair through upregulation of STAT1 expression can protect TEC function, reduce stone formation, and activating STAT1 function can also achieve the goal of treating kidney stones.

Acute kidney disease in mice is associated with early cardiovascular dysfunction

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity—indoxyl sulfate (IS) and para-cresyl sulfate (PCS)—and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study.

Analysis of influencing factors of acute kidney injury after unilateral nephrectomy

Unilateral Nephrectomy is one of the most common treatments for surgical diseases of the kidney but often results in postsurgical acute kidney injury (AKI). In the current study, we aimed to investigate the risk factors for AKI in patients who have received Unilateral Nephrectomy. We retrospectively analysed 528 patients who underwent Unilateral Nephrectomy for different etiologies between January 2013 and December 2018 at the Affiliated Hospital of Qingdao University. We recorded the prevalence and severity of AKI, age, gender, diabetes, body mass index (BMI), hypertension, preoperative renal function, etiology, performed surgically, anaemia, albumin, coagulation, lactate dehydrogenase, nitrogen (BUN), and uric acid. Univariate and multivariate logistic regression analyses were used to investigate the predictors of AKI in patients with Unilateral Nephrectomy. Overall, 218 of the 528 patients (41.2%) developed AKI during their hospitalisation. Univariate analysis showed that AKI was significantly associated with gender (male, OR = 1.866, P = 0.001), overweight (OR = 2.19, P = 0.0002), and surgical approach (OR = 1.7, P = 0.018), while multivariate logistic regression analysis showed that male gender (OR = 1.953, P = 0.001), overweight (OR = 2.176, P = 0.001), and preoperative renal function (OR = 0.507, P = 0.001) were independent factors for AKI. Regression analysis among different etiologies showed significant differences in postoperative AKI. After Unilateral nephrectomy, AKI is more likely to occur in overweight male patients with normal kidney function. AKI occurred more frequently in patients who are kidney donors, but rarely in those with non-function kidneys.

Early Prediction of Acute Kidney Injury in Living Donor Liver Transplantation by Serum Cystatin C Concentration at the End of the Surgery.

Acute kidney injury (AKI) is a prevalent complication of liver transplantation, leading to prolonged hospital or intensive care unit stay and significant morbidity. Recently, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have been investigated for their potential role in the early detection of AKI in liver transplantation patients. Our study comprised 60 patients with end-stage liver disease undergoing living donor liver transplantation. Based on the postoperative development of AKI, the patients were categorised into two groups: the AKI group comprising 22 patients and the non-AKI group comprising 38 patients. Serum cystatin C and urine NGAL levels were measured twice: immediately after induction of anaesthesia (baseline) and at the end of the surgery. The overall incidence of AKI was 36.66%. The mean cystatin C level measured at the end of the surgery was significantly higher in the AKI group (1.12 ± 0.40 mg/L) than in the non-AKI group (0.82 ± 0.27 mg/L) [P = .001]. The receiver operating characteristic curve for the postoperative cystatin C biomarker demonstrated a significant difference between the AKI and non-AKI groups [area under the curve: 0.71, P = .007]. However, baseline cystatin C and urine NGAL levels did not significantly differ between the groups. Cystatin C levels measured at the end of the surgery showed a better predictive value and higher accuracy in identifying post-liver transplantation patients with AKI than baseline cystatin C and urine NGAL.

Absence of Kidney Tubular Injury in Patients With Acute Heart Failure With Acute Kidney Injury.

Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes. We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC). Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome. Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population. URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836.

Clove Aqueous Extract Alleviates Acute Kidney Injury Induced by Folic Acid in Rats

Background: Acute Kidney Injury (AKI) is a common clinical disease that has a high incidence and mortality rate. Clove, a robust natural source of bioactive chemicals and rich in secondary metabolites, plays a wide range of biological roles. Aim: The present study aimed to assess the ameliorative efficacy of clove extract against acute renal damage induced by folic acid in rats. Methods: Gas Chromatography/Mass Spectrometry (GC/MS) was used to investigate the main components of clove extract. Folic acid, at a dose of 250 mg/kg, was delivered intraperitoneally to rats to induce AKI. Eighteen rats were divided into three groups: control, AKI, and AKI + clove extract (500 mg/kg). Results: The administration of clove extract significantly restored the levels of creatine, urea, uric acid, sodium, potassium, chloride, creatinine clearance, and microalbumin to nearly normal levels. Also, clove water extract inhibited oxidative stress by decreasing concentrations of Malondialdehyde (MDA) and Nitric Oxide (NO). Furthermore, clove extract elevated the levels of Glutathionereduced (GSH), Catalase (CAT), and Glutathione S-transferase (GST). Kidney section histology showed notable improvements after the administration of clove extract. Conclusion: The clove water extract has been found to contain many bioactive components possessing antioxidant and anti-inflammatory properties, effectively protecting against acute renal injury.

Adverse reaction of specific acute kidney injury caused by atorvastatin: an actual study based on the database of the US FDA adverse event reporting system

ABSTRACT Introduction Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin. Areas Covered Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups. Expert Opinion In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

Predictive value of triglyceride glucose index in acute kidney injury in patients with severe traumatic brain injury

Background At present, the relationship between the Triglyceride-glucose index (TyG index) and Acute kidney injury (AKI) in traumatic brain injury patients in the Intensive Care Unit (ICU) is still unclear. Currently, the relationship between TyG index and AKI occurred within 7 days in the ICU is a highly researched and trending topic. Objective In this study, we conducted in-depth exploration of the relationship between the development of AKI in traumatic brain injury (TBI) patients in the ICU and changes in TyG index, as well as its relevance. Methods A cross-sectional study was conducted with a total of 492 individuals enrolled in the Medical Information Mart for Intensive Care IV(MIMIC-IV) database. Multivariate model logistic regression, smoothed curve fitting and forest plots were utilized to confirm the study objectives. The predictive power of the TyG index for outcome indicators was assessed using subject work characteristics (ROC) curves. As well as comparing the Integrated Discriminant Improvement Index and the Net Reclassification Index of the traditional forecasting model with the addition of the TyG index. Results Of all eligible subjects, 55.9% were male and the incidence of AKI was 59.3%. There was a statistically significant difference in the incidence of AKI within 7 days in the ICU between the different TyG index groups. The difference between TyG index and the risk of AKI within 7 days in the ICU remained significant after adjustment for logistic multifactorial modeling (OR = 2.07, 95% CI = 1.41–3.05, P < 0.001). A similar pattern of associations was observed in subgroup analyses (P values for all interactions were greater than 0.05). The addition of TyG index to the traditional risk factor model improved the predictive power of the risk of AKI within 7 days in ICU (P < 0.05). Conclusion The findings of this study demonstrate a strong association between the TyG index and the occurrence of AKI within 7 days in ICU patients. The TyG index can potentially be used as a risk stratification tool for early identification and prevention of AKI. Implementing preventive strategies targeting patients with a high TyG index may help reduce the burden of AKI in the ICU. Further prospective studies are warranted to validate these findings and explore the clinical utility of the TyG index in AKI prevention.

Dietary Probiotic Pediococcus acidilactici GKA4, Dead Probiotic GKA4, and Postbiotic GKA4 Improves Cisplatin-Induced AKI by Autophagy and Endoplasmic Reticulum Stress and Organic Ion Transporters

Background/Objectives: Acute kidney injury (AKI) syndrome is distinguished by a quick decline in renal excretory capacity and usually diagnosed by the presence of elevated nitrogen metabolism end products and/or diminished urine output. AKI frequently occurs in hospital patients, and there are no existing specific treatments available to diminish its occurrence or expedite recovery. For an extended period in the food industry, Pediococcus acidilactici has been distinguished by its robust bacteriocin production, effectively inhibiting pathogen growth during fermentation and storage. Methods: In this study, the aim is to assess the effectiveness of P. acidilactici GKA4, dead probiotic GKA4, and postbiotic GKA4 against cisplatin-induced AKI in an animal model. The experimental protocol involves a ten-day oral administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 to mice, with a cisplatin intraperitoneal injection being given on the seventh day to induce AKI. Results: The findings indicated the significant alleviation of the renal histopathological changes and serum biomarkers of GKA4, dead probiotic GKA4, and postbiotic GKA4 in cisplatin-induced nephrotoxicity. GKA4, dead probiotic GKA4, and postbiotic GKA4 elevated the expression levels of HO-1 and decreased the expression levels of Nrf-2 proteins. In addition, the administration of GKA4, dead probiotic GKA4, and postbiotic GKA4 significantly reduced the expression of apoptosis-related proteins (Bax, Bcl-2, and caspase 3), autophagy-related proteins (LC3B, p62, and Beclin1), and endoplasmic reticulum (ER) stress-related proteins (GRP78, PERK, ATF-6, IRE1, CHOP, and Caspase 12) in kidney tissues. Notably, GKA4, dead probiotic GKA4, and postbiotic GKA4 also upregulated the levels of proteins related to organic anion transporters and organic cation transporters. Conclusions: Overall, the potential therapeutic benefits of GKA4, dead probiotic GKA4, and postbiotic GKA4 are significant, particularly after cisplatin treatment. This is achieved by modulating apoptosis, autophagy, ER stress, and transporter proteins to alleviate oxidative stress.

Integrated temporal transcriptional and epigenetic single-cell analysis reveals the intrarenal immune characteristics in an early-stage model of IgA nephropathy during its acute injury

RationaleKidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.ObjectiveWe aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).Methods and resultsA murine model was utilized to mimic 3 immunological states –”immune stability (IS), immune activation (IA) and immune remission (IR)” in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.ConclusionsThis study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.

Exploring the Key Pathogenesis and Potential Intervention Targets of Sulforaphane in Acute Kidney Injury in Sepsis Based on Bioinformatics.

The objective was to use bioinformatics to analyze the potential key genes involved in the mechanism of sulforaphane's protective effects in sepsis-associated acute kidney injury (SA-AKI) and to identify potential intervention targets. Gene Expression Omnibus (GEO) gene chip datasets containing gene expression profiles from kidney tissues of SA-AKI patients and normal controls were selected. Upregulated differentially expressed genes (DEGs) were identified using GEO2R. Protein-protein interaction (PPI), GO, and KEGG enrichment analyses were performed. Allyl isothiocyanate's target genes were analyzed in the ChEMBL database, and intersections with the above DEGs were presented in Venn diagrams. Rat tissues were examined for FKBP1A expression using qRT-PCR. A total of 17 DEGs related to SA-AKI were obtained (|log fold change| > 0 and P < .05). KEGG pathway analysis indicated that the primary pathways linked to the elevated DEGs were glycogen breakdown, leukocyte trans-endothelial migration, and T-cell receptor, TNF, and NF-κB signaling. The module and PPI network analysis of common DEGs revealed one cluster and four candidate genes, including OASL, TRRAP, FKBP1A, and BANF. ChEMBL database analysis identified 339 target genes for allyl isothiocyanate, and the intersection with upregulated DEGs related to SA-AKI injury yielded two co-expressed genes, FKBP1A and TRRAP. According to the findings of the qRT-PCR assay, the kidney tissues of the model cohort showed significantly higher expression levels of FKBP1A mRNA than the control cohort (P = .0142). Allyl isothiocyanate may alleviate SA-AKI injury by targeting FKBP1/NF-κB.

Erratum:Trends in Research on Acute Kidney Injury: A Bibliometric Analysis of Academic Journals Published Between the Years 2000 and 2022.

Erratum:Trends in Research on Acute Kidney Injury: A Bibliometric Analysis of Academic Journals Published Between the Years 2000 and 2022.