New drugs for acute kidney injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Pickkers P
PROVIDER: S-EPMC9705447 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
New drugs for acute kidney injury.
Pickkers Peter P Murray Patrick T PT Ostermann Marlies M
Intensive care medicine 20220823 12
Similar Datasets
Project description:Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs.
| S-EPMC11297046 | biostudies-literature
Project description:Objective: To provide insights into the diagnosis and therapy of SA-AKI via ferroptosis genes. Methods: Based on three datasets (GSE57065, GSE30718, and GSE53771), we used weighted co-expression network analysis to identify the key regulators of SA-AKI, its potential biological functions, and constructed miRNA‒mRNA complex regulatory relationships. We also performed machine learning and in vitro cell experiments to identify ferroptosis genes that are significantly related to SA-AKI in the two datasets. The CIBERSORT algorithm evaluates the degree of infiltration of 22 types of immune cell. We compared the correlation between ferroptosis and immune cells by Pearson's correlation analysis and verified the key genes related to the immune response to reveal potential diagnostic markers. Finally, we predicted the effects of drugs and the potential therapeutic targets for septic kidney injury by pRRophetic. Results: We found 264 coDEGs involving 1800 miRNA molecules that corresponded to 210 coDEGs. The miRNA‒mRNA ceRNA interaction network was constructed to obtain the top-10 hub nodes. We obtained the top-20 ferroptosis genes, 11 of which were in the intersection. We also identified a relationship between ferroptosis genes and the immune cells in the AKI dataset, which showed that neutrophils were activated and that regulatory T cells were surpassed. Finally, we identified EHT1864 and salubrinal as potential therapeutic agents. Conclusion: This study demonstrated the roles of miR-650 and miR-296-3p genes in SA-AKI. Furthermore, we identified OLFM4, CLU, RRM2, SLC2A3, CCL5, ADAMTS1, and EPHX2 as potential biomarkers. The irregular immune response mediated by neutrophils and Treg cells is involved in the development of AKI and shows a correlation with ferroptosis genes. EHT 1864 and salubrinal have potential as drug candidates in patients with septic acute kidney injury.
| S-EPMC9792148 | biostudies-literature
Project description:Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.
| S-EPMC9283743 | biostudies-literature
Project description:Background and objectivesLittle is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials.Design, setting, participants, & measurementsWe systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials.ResultsIn the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis.ConclusionsCurrent evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
| S-EPMC7792639 | biostudies-literature
Project description:The goal of this observational study is to compare anesthetic modalities (intravenous propofol anesthesia with sevoflurane gas anesthesia) in patients who underwent colorectal cancer resection surgery regarding the outcome of acute kidney injury.
The main questions it aims to answer are:
* is there a difference in acute kidney injury incidence in the two anesthetic modalities?
* is there a difference in plasma creatinine between the two anesthetic modalities?
* are there any patient characteristics or intraoperative factors that effect the incidence of acute kidney injury in either anesthetic modality?
The study will analyze data from the CAN clinical trial database. (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia, NCT01975064)
| 2751857 | ecrin-mdr-crc
Project description: Not available
| S-EPMC7491389 | biostudies-literature
Project description:BackgroundWe sought to comprehensively describe drug-related components associated with acute kidney injury (AKI) in patients with chronic kidney disease (CKD), describing the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the 1-year incidences of the recurrence of drug-related AKI, kidney failure, and death.MethodsCKD-REIN is a French national prospective cohort of 3033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 ml/min/1.73 m²). AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital reports, medical records, and patient interviews. Expert nephrologists used the KDIGO criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs).ResultsOver a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3033 study participants. The drug-related component associated with AKI accounted for 236 cases, and 28% were judged to be preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. A history of cardiovascular events, diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs taken daily were associated with a greater risk of drug-related AKI. Full recovery was not attained in 64 (27%) of the 236 cases of drug-related AKI. The 1-year cumulative incidences of recurrence of drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI.ConclusionsDrug-related AKI is prevalent among patients with CKD. Even though a substantial proportion of these events were classified as stage 1, our findings point to a poor prognosis.
| S-EPMC11707387 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) and chronic kidney disease (CKD) have become worldwide public health problems, but little information is known about the epidemiology of acute kidney disease (AKD)-a state in between AKI and CKD. We aimed to explore the incidence and outcomes of hospitalized patients with AKD after AKI, and investigate the prognostic value of AKD in predicting 30-day and one-year adverse outcomes.MethodsA total of 2,556 hospitalized AKI patients were identified from three tertiary hospitals in China in 2015 and followed up for one year.AKD and AKD stage were defined according to the consensus report of the Acute Disease Quality Initiative 16 workgroup. Multivariable regression analyses adjusted for confounding variables were used to examine the association of AKD with adverse outcomes.ResultsAKD occurred in 45.4% (1161/2556) of all AKI patients, 14.5% (141/971) of AKI stage 1 patients, 44.6% (308/691) of AKI stage 2 patients and 79.6% (712/894) of AKI stage 3 patients. AKD stage 1 conferred a greater risk of Major Adverse Kidney Events within 30 days (MAKE30) (odds ratio [OR], 2.36; 95% confidence interval 95% CI [1.66-3.36]) than AKD stage 0 but the association only maintained in AKI stage 3 when patients were stratified by AKI stage. However, compared with AKD stage 0, AKD stage 2-3 was associated with higher risks of both MAKE30 and one-year chronic dialysis and mortality independent of the effects of AKI stage with OR being 31.35 (95% CI [23.42-41.98]) and 2.68 (95% CI [2.07-3.48]) respectively. The association between AKD stage and adverse outcomes in 30 days and one year was not significantly changed in critically ill and non-critically ill AKI patients. The results indicated that AKD is common among hospitalized AKI patients. AKD stage 2-3 provides additional information in predicting 30-day and one-year adverse outcomes over AKI stage. Enhanced follow-up of renal function of these patients may be warranted.
| S-EPMC8158174 | biostudies-literature
Project description:Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various pharmacologic or nonpharmacologic interventions, reliable means to prevent or reverse acute kidney injury are still lacking. Nevertheless, several recent randomized multicenter trials provide new insights into renal replacement strategies, composition of intravenous fluid replacement, goal-directed fluid therapy, or remote ischemic preconditioning in their impact on perioperative acute kidney injury. This review provides an update on the latest progress toward the understanding of disease mechanism, diagnosis, and managing perioperative acute kidney injury, as well as highlights areas of ongoing research efforts for preventing and treating acute kidney injury in surgical patients.
| S-EPMC10924686 | biostudies-literature
Project description:The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled. The result is a lower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect at a given sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factors as eligibility criteria for trial enrollment in early AKI has the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. In the hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease the sample size, and lower the cost of AKI trials.
| S-EPMC4869991 | biostudies-literature