Nephrotoxic Drugs Research Articles

Point of care creatinine testing for early detection of renal dysfunction in Tanzanian HIV patients: a study protocol

BackgroundRenal dysfunction (RD) is more prevalent among people living with HIV (PLHIV) in sub-Saharan Africa (SSA) due to factors such as co-infections, hypertension, diabetes, and nephrotoxic antiretroviral drugs like tenofovir. Early detection of RD is critical but limited by resource constraints in many SSA countries, including Tanzania. Point-of-care (POC) tests, such as the Stat-Sensor Creatinine test by Nova Biomedical, present a cost-effective and non-invasive option for early detection. This study will evaluate the diagnostic performance of the Stat-Sensor creatinine test in detecting renal dysfunction in HIV care and treatment clinics (CTCs) in Tanzania. It will be conducted for a period of six months, from November 2024 to April 2025.MethodologyThe study will measure point-of-care creatinine using a rapid creatinine dipstick against the standard serum creatinine test. The diagnostic performance and agreement to diagnose renal dysfunction will be assessed using a standardized statistical approach: Bland-Altman analysis and linear mixed-effects models to test agreement between creatinine dipstick tests with serum creatinine. Receiver operating characteristics (ROC) statistics will be used to test the diagnostic performance of the creatinine dipstick test to diagnose renal dysfunction.DiscussionWe hypothesize that POC creatinine testing will show strong diagnostic performance, providing a reliable, rapid, and cost-efficient alternative for RD detection, leading to better patient outcomes and integration of POC tests into routine HIV care.Ethical clearanceThe study protocol was reviewed and approved by the Muhimbili University of Health and Allied Sciences Research and Publication committee in June 2024 with reference number, MUHAS-REC-05-2024-2275.

A Systematic Review of the Costs of Drug-Associated Acute Kidney Injury and Potential Cost Savings with Nephrotoxin Stewardship Prevention Strategies.

There is a scarcity of information related to the financial impact of acute kidney injury (AKI), and even more so the economics of drug-associated AKI (D-AKI). Our goal was to provide a comprehensive summary of the economic burden of D-AKI by evaluating the costs of D-AKI compared to not developing AKI and cost savings associated with nephrotoxin stewardship approaches. Following the PRISMA guidelines, a literature search was conducted using PubMed to identify articles from database inception through November 2023. The main outcomes included AKI incidence, resource use, and cost of nephrotoxin stewardship programs/D-AKI event or no event. Key findings were summarized based on whether the study compared the cost of D-AKI vs. no AKI or identified potential cost savings associated with a nephrotoxin stewardship method to prevent D-AKI or worsening D-AKI. All costs were adjusted to USD2023. Twenty-five studies met the inclusion criteria. Eight studies compared the cost of D-AKI to no AKI. Total admission costs of patients who developed D-AKI ranged from $47,696 to $173,569. Nineteen studies implemented nephrotoxin stewardship with 12 substituting a less nephrotoxic drug; five using therapeutic drug monitoring and two altering drug dosing to limit exposure. Overall, these prevention strategies ranged from $5,171 to $364,973 in total medical cost savings and $17 to $942 in total cost savings per patient-day. The in-hospital economic impact of D-AKI is substantial. Implementing nephrotoxin stewardship strategies to reduce D-AKI is associated with cost savings. Institutions should adopt strategic and efficient nephrotoxin stewardship programs to optimize patient care and reduce costs.

Does serum neutrophil gelatinase–associated lipocalin level predict acute kidney injury in patients with acute rhabdomyolysis in the emergency department? A multicentre prospective study

ObjectivesThe major complication of rhabdomyolysis is acute kidney injury (AKI), which requires prompt treatment. Currently, few biomarkers are available for the early detection of AKI. Serum neutrophil gelatinase–associated lipocalin (NGAL) has been suggested as an early biomarker for renal ischemia. However, its capacity to predict AKI in patients presenting with rhabdomyolysis in the emergency department (ED) remains unclear. The aim of this study was to evaluate the ability of NGAL to predict 48-hour AKI.DesignProspective, multicentre study.SettingFive adult EDs in France from August 2013 to December 2015.ParticipantsNGAL levels were measured on ED admission in patients with rhabdomyolysis. A total of 197 patients were enrolled, and 189 (96%) were analysed, of whom 89 (47%) were women. Patients were included if they presented to the ED with rhabdomyolysis and a creatine phosphokinase (CPK) level above 1000 IU/L. Exclusion criteria were pregnancy, presentation with acute coronary syndrome, the need for iodinated contrast, chronic dialysis or recent use of nephrotoxic drugs (within 72 hours prior to the ED visit). Patients who withdrew consent or had AKI due to other causes were also excluded.Primary and secondary outcome measuresThe primary outcome was AKI at 48 hours, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included in-hospital mortality, length of hospital stay, admission to intensive care and the need for renal replacement therapy.ResultsOverall, 54 (29%) patients developed AKI by day 2. The area under the ROC curve (AUC-ROC) for NGAL in predicting AKI on day 2 was 0.60 (95% CI 0.51 to 0.70), with an optimal cut-off of 129 ng/mL. The sensitivity was 0.65, and specificity was 0.50. After adjustment for CPK levels, age, sex and oxygen saturation, the AUC-ROC for predicting AKI on day 2 increased slightly to 0.64 (95% CI 0.54 to 0.74).ConclusionNGAL has limited ability to predict day 2 AKI in patients presenting with acute rhabdomyolysis in the ED.Trail registration numberNCT01544231.Comité de Protection des Personnes Sud Méditerranée III n°2011-A01059-32.

Construction and Evaluation of Hepatic Targeted Drug Delivery System with Hydroxycamptothecin in Stem Cell-Derived Exosomes.

Hydroxycamptothecin (HCPT) is commonly used in the treatment of liver cancer; however, its low water solubility and poor stability significantly limit its clinical application. In recent years, research on exosomes has deepened considerably. Exosomes possess a unique phospholipid bilayer structure, enabling them to traverse tissue barriers, which provides natural advantages as drug carriers. Nevertheless, delivering exosomes safely and efficiently to target cells remains a major challenge. In this study, we utilized the affinity of the SP94 peptide for human liver cancer cell receptors. HCPT was coated with exosomes in our experimental design, and the exosome membrane was modified with SP94 peptide to facilitate drug delivery to liver cancer cells. Exosomes were purified from bone marrow mesenchymal stem cells, and targeted peptides were attached to their surfaces via post-insertion techniques. Subsequently, HCPT was incorporated into the exosomes through electroporation. Using the HepG2 hepatoma cell line, we evaluated a series of in vitro pharmacodynamics and studied pharmacokinetics and tissue distribution in animal models. The results indicated that ligand-targeted, modified drug-carrying exosomes significantly enhance drug bioavailability, prolong retention time in vivo, and facilitate liver targeting. Moreover, this approach reduces drug nephrotoxicity, enhances anti-tumor efficacy, and lays the groundwork for the development of novel liver cancer-targeting agents.

Drug-induced acute kidney injury: a cohort study on incidence, identification of pathophysiological mechanisms, and prognostic factors.

Acute Kidney Injury (AKI) is a common clinical syndrome characterized by an abrupt decline in the glomerular filtration rate (GFR), which can cause severe alterations in blood volume and acid-base balance. Drug-Induced Acute Kidney Injury (DI-AKI) is associated with exposure to nephrotoxic medications, particularly among hospitalized patients. Adverse drug reactions comprises type A and type B reactions. Type A reactions are predictable based on the pharmacology of the substance, dose-dependent, and manifest as Acute Tubular Necrosis (ATN). Type B reactions are unpredictable, idiosyncratic, not dose-dependent, and manifest as Acute Interstitial Nephritis (AIN), Crystal-Induced Nephropathy, among others. To evaluate DI-AKI incidence, identify the main associated drugs and the pathophysiological mechanism of the observed injury, analyze prognostic factors associated with unfavorable outcomes, and compare the outcomes of death and the need for Acute Kidney Support Therapy (AKST) between patients with DI-AKI vs. AKI due to other etiologies. A retrospective cohort study conducted at the Hospital das Clínicas of the Faculty of Medicine of Botucatu - UNESP (HC-FMB), using data from patients hospitalized between January 2016 and April 2022 and followed, via consultation, by the AKI-Nephrology team. Inclusion criteria: diagnosis of AKI and Chronic Kidney Disease (CKD) with superimposed AKI. Exclusion criteria: patients under 18 years old or on chronic Renal Replacement Therapy. AKI was diagnosed based on creatinine increase as established by KDIGO 2012. Data were presented as mean and standard deviation or median with interquartile range and frequency. Statistical significance was set at 5% (p < 0.05). Comparative analyses were performed using the Chi-Square test for categorical variables and the T-test for continuous variables. Subsequently, logistic regression was performed to identify factors associated with the need for AKST and death. A total of 1,398 patients were analyzed, most of them males (61.4%), with a mean age of 64 years ±14.4 years. The most prevalent etiology of AKI was Mixed Ischemic + Septic AKI (28%). DI-AKI was a significant cause of AKI (19.3%). Of these, 25.2% were isolated DI-AKI and 74.8% were Mixed DI-AKI + Ischemia and/or Sepsis. Among patients with DI-AKI, the mean age was 61.15 ± 15.26, males were the most frequent, the majority were not subjected to AKST and survived. Most of these patients were hospitalized in the ward, did not need vasoactive drugs, nor did they use mechanical ventilation. DI-AKI showed lower severity and mortality compared to other AKI etiologies but had a similar need for AKST (26.3% vs. 35.4%, p < 0.05 and 31.8% vs. 36.8%, p > 0.05). Most nephrotoxic drugs caused type A reactions, with Vancomycin being the primary nephrotoxin. Among drugs associated with DI-AKI, Vancomycin was associated with a higher need for AKST and death, while Amphotericin B was associated with a lower risk of AKST and death. Although the mortality rate is lower among DI-AKIs compared to other AKI etiologies, the need for AKST was similar. Therefore, it is recommended that DI-AKI be recognized early to enable dose reduction or even drug suspension, depending on the type of reaction, to reduce healthcare costs and improve clinical outcomes for patients.

Dynamic Kidney Organoid Microphysiological Analysis Platform.

Kidney organoids, replicating human development, pathology, and drug responses, are a promising model for advancing bioscience and pharmaceutical innovation. However, reproducibility, accuracy, and quantification challenges hinder their broader utility for advanced biological and pharmaceutical applications. Herein, we present a dynamic kidney organoid microphysiological analysis platform (MAP), designed to enhance organoid modeling and assays within physiologically relevant environments, thereby expanding their utility in advancing kidney physiology and pathology research. First, precise control of the dynamic microenvironment in MAP enhances the ability to fine-tune nephrogenic intricacies, facilitating high-throughput and reproducible human kidney organoid development. Also, MAP's miniaturization of kidney organoids significantly advances pharmaceutical research by allowing for detailed analysis of entire nephron segments, which is crucial for assessing the nephrotoxicity and safety of drugs. Furthermore, the MAP's application in disease modeling faithfully recapitulates pathological development and functions as a valuable testbed for therapeutic exploration in polycystic kidney diseases. We envision the kidney organoid MAP enhancing pharmaceutical research, standardizing processes, and improving analytics, thereby elevating the quality and utility of organoids in biology, pharmacology, precision medicine, and education.

Clinical Profile And Aetiology of Acute Kidney Injury Developing In Patients Hospitalized Due To Non-Renal Cause With Pre-Existing Normal Renal Function

Background: Acute kidney injury (AKI) is a common complication in patients hospitalized for non-kidney disease and having normal renal function. Early detection of development of deteriorating renal function and assessment of its cause can help to manage the cases effectively and can prevent further kidney damage or progression to end stage renal failure. Methods: This observational study was done on 50 patients selected from the departments of Medicine and Nephrology of Dhaka Medical College (DMCH) and BSMMU, from June 2012 to November 2012. Patients were included in the study who developed clinical features and biochemical findings of acute kidney injury, while being admitted with various non-renal diseases and had previous normal renal function. Results: In this study the cause of deterioration of renal function was Sepsis in 44.0% of the patients, 42.0% had fluid loss, 6.0% had used nephrotoxic drugs, 4.0% had hepatitis, 2.0% patients each had pancreatitis and insect bite respectively. 40% of the patients were above 40 years of age, 54% were male. Vomiting was present in 42% of the patients and diarrhoea in 20% of the patients. 26% patients had DM and 22% had hypertension. Conclusion: Sepsis and hypovolemia were the common causes of developing acute kidney injury in the hospital. In-hospital mortality was 18.0% and 22.0% patients developed CKD after three months follow-up. J Dhaka Med Coll. 2023; 32(1) : 85-91

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.

Risk factors for acute kidney injury in children with critical illness

Background Acute kidney injury (AKI) is an acute functional kidney disorder that increases morbidity and mortality in children. The mortality rate for critically ill patients accompanied by AKI is quite high and is influenced by the degree of AKI, the severity of the disease, and organ function disorders. Understanding the risk factors of developing AKI in children with critical illness can help prevent AKI. Objective To determine the risk factors for AKI in children with critical illness. Methods This retrospective cohort study included 255 children aged 1 month to 18 years admitted at the pediatric intensive care unit (PICU) of dr. Zainoel Abidin Regional Public Hospital, Banda Aceh, Aceh, from January to December 2022 using medical record data. Bivariate and multivariate analyses were performed. Results Acute kidney injury occurred in 68 (26.7%) patients. Based on pRIFLE criteria, 34 (50%) patients had AKI in the failure stage. Risk factors for AKI in children with critical illness were in descending order of RR: sepsis (RR 14.3; 95%CI 11.68 to 18.66; P=0.000), mechanical ventilation (RR 12.13; 95%CI 8.75 to 15.98; P=0.000), respiratory disorders (RR 2.51; 95%CI 2.06 to 4.02; P=0.003), congenital heart disease (RR 2.08; 95%CI 2.00 to 3.05; P=0.004), CNS disorders (RR 1.24; 95%CI 1.02 to 2.49; P=0.048), nephrotoxic drug use (RR 1.41; 95%CI 1.24 to 3.08; P=0.000), and age 1 month to 5 years (RR 0.072; 95%CI 0.16 to 0.32; P=0.010). Conclusion Sepsis is a risk factor for AKI in children with critical illness, followed by mechanical ventilation use, respiratory disorders, nephrotoxic drug use. Age &lt;5 years is a protective factor.

Galangin prevents gentamicin-induced nephrotoxicity by modulating oxidative damage, inflammation and apoptosis in rats.

The well-known antibiotic gentamicin (GEN) works well against a variety of pathogenic bacteria, nevertheless its therapeutic use might be limited by the possibility of nephrotoxicity. The naturally occurring flavonoid galangin (GAL) has several interesting anti-inflammatory and antioxidant properties. The present study evaluated the nephroprotective effect of GAL on GEN-induced renal injury. Rats received GAL for 14 days and GEN from day 8 to day 14. There was a significant increase in serum urea and creatinine along with several histopathological changes in the kidney following GEN administration. GEN-treated rats also showed increased levels of kidney MDA and NO, and decreased GSH content and activities of antioxidant enzymes. Rats received GEN also demonstrated increased NF-κB p65, iNOS, TNF-α, IL-1β and IL-6 levels in the kidney. GAL remarkably prevented tissue injury, attenuated MDA and NO levels, improved antioxidants, and decreased levels of inflammatory mediators in the kidney of GEN-treated rats. Furthermore, GEN-administrated rats exhibited increased Bax and caspase-3 with concomitant decline in Bcl-2 levels in the kidney, an effect that GAL attenuated. In conclusion, GAL prevents GEN-induced nephrotoxicity by attenuating oxidative stress, inflammation, and apoptosis and augmenting antioxidant defense, suggesting its therapeutic potential against drug nephrotoxicity.

Preterm Birth and Kidney Health: From the Womb to the Rest of Life.

Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care.

Simultaneous Percutaneous Coronary Intervention (PCI) and Endovascular Aneurysm Repair (EVAR): A Preliminary Report.

Background: Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI-EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods: Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results: Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180-240 min), the average fluoroscopy duration was 41.7 min (range: 35-50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30-40 mL), and the mean length of hospitalization was 2.7 days (range: 2-5 days). Conclusions: In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

Unveiling the Landscape of Acute Kidney Injury in Surgical Patients: A Systematic Review of Risk Factors and Clinical Biomarkers

Acute Kidney Injury (AKI) is a critical complication with significant implications for surgical patients, leading to increased morbidity, mortality, and healthcare costs. Identifying the risk factors and clinical biomarkers associated with AKI in the surgical context is essential for timely intervention and personalized management. To address this knowledge gap, we conducted a systematic review to comprehensively analyze existing literature on AKI in surgical patients. In this paper, we provided a systemically review analysis based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique for AKI risk factors and clinical biomarkers. The advanced searching into two powerful databases which is Scopus, Pubmed and Mendeley. Based on searching, find finally main data n=30 and will be analyzed using the synthesis approach. Through a meticulous search and appraisal of studies in reputable scientific databases, we identified a diverse range of research articles, clinical trials, and cohort studies that met our rigorous inclusion criteria. Synthesizing the findings from these studies, we explored the multifactorial nature of AKI, encompassing patient-related factors, surgical variables, and exposure to potential nephrotoxic agents. Our review revealed that AKI in surgical patients is influenced by a complex interplay of risk factors, including patient demographics, comorbidities, surgical procedures, anaesthetic management, and exposure to nephrotoxic drugs. The systematic analysis identified the most common drug classes associated with drug-induced AKI, such as diuretics, ACE inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and antibiotics

The Acute Kidney Intervention and Pharmacotherapy (AKIP) List: Standardized List of Medications That Are Renally Eliminated and Nephrotoxic in the Acutely Ill.

The objective of this project was to develop a standardized list of renally eliminated and potentially nephrotoxic drugs that will help inform initiatives to improve medication safety. Several available lists of medications from the published literature including original research articles and reviews, and from regulatory agencies, tertiary references, and clinical decision support systems were compiled, consolidated, and compared. Only systemically administered medications were included. Medication combinations were included if at least 1 active ingredient was considered renally dosed or potentially nephrotoxic. The medication list was reviewed for completeness and clinical appropriateness by a multidisciplinary team of individuals with expertise in critical care, nephrology, and pharmacy. An initial list of renally dosed and nephrotoxic drugs was created. After reconciliation and consensus from clinical experts, a standardized list of 681 drugs is proposed. The proposed evidence-based standardized list of renally dosed and potentially nephrotoxic drugs will be useful to harmonize epidemiologic and medication quality improvement studies. In addition, the list can be used for clinical purposes with surveillance in nephrotoxin stewardship programs. We suggest an iterative re-evaluation of the list with emerging literature and new medications on an approximately annual basis.

Nanotechnology-Based Drug Delivery Systems for Treating Acute Kidney Injury.

Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.

Renal dysfunction in surgical patients.

To provide an overview of the current diagnostic criteria for acute kidney injury (AKI) including their limitations and to discuss prevention and treatment approaches in the perioperative setting. AKI is common in the perioperative period and is associated with worse short- and long-term outcomes. Current definitions of AKI have several limitations and lead to delayed recognition of kidney dysfunction which is why novel diagnostic approaches by using renal biomarkers may be helpful. In general, prevention of the development and progression of AKI is vital as a causal treatment for AKI is currently not available. Optimization of kidney perfusion and avoidance of nephrotoxic drugs reduce the occurrence of AKI in surgical patients. Angiotensin II as a new vasopressor, the use of remote ischemic preconditioning, and amino acids may be approaches with a positive effect on the kidneys. Evidence suggests that the implementation of supportive measures in patients at high risk for AKI might reduce the occurrence of AKI. Novel biomarkers can help allocating resources by detecting patients at high risk for AKI.

Polymyxin B vs. colistin: the comparison of neurotoxic and nephrotoxic effects of the two polymyxins

BackgroundThe study aimed to compare polymyxin B with colistimethate sodium (CMS) regarding neurotoxicity, nephrotoxicity and 30-day mortality in patients with MDR Gram-negatives.MethodsAll adult patients who received polymyxin B or CMS for at least 24 h for the treatment of MDR microorganisms were evaluated retrospectively.ResultsAmong 413 initially screened patients, 147 patients who were conscious and able to express their symptoms were included in the neurotoxicity analysis. 13 of 77 patients with polymyxin B and 1 of 70 with CMS had neurotoxic adverse events, mainly paresthesias. All events were reversible after drug discontinuation. Among 290 patients included in nephrotoxicity analysis, the incidence of acute kidney injury (AKI) was 44.7% and 40.0% for polymyxin B and CMS, respectively (p = 0.425). AKI occurred two days earlier with colistin than polymyxin B without statistical significance (median (IQR): 5 (3–11) vs. 7 (3–12), respectively, p = 0.701). Polymyxin therapy was withdrawn in 41.1% of patients after AKI occurred and CMS was more frequently withdrawn than polymyxin B (p = 0.025). AKI was reversible in 91.6% of patients with CMS and 79% with polymyxin B after the drug withdrawal. Older age, higher baseline serum creatinine and the use of at least two nephrotoxic drugs were independent factors associated with AKI (OR 1.05, p < 0.001; OR 2.99, p = 0.022 and OR 2.45, p = 0.006, respectively). Septic shock, mechanical ventilation, presence of a central venous catheter and Charlson comorbidity index (OR 2.13, p = 0.004; OR 3.37, p < 0.001; OR 2.47, p = 0.004 and OR 1.21, p p < 0.001, respectively) were the independent predictors of mortality. The type of polymyxin was not related to mortality.ConclusionsNeurotoxicity is a relatively common adverse event that leads to drug withdrawal during polymyxins, particularly polymyxin B. Nephrotoxicity is very common during polymyxin therapy and the two polymyxins display similar nephrotoxic events with high reversibility rates after drug withdrawal. Close monitoring of AKI is crucial during polymyxin therapy, particularly, for elderly patients, patients who have high baseline creatinine, and using other nephrotoxic drugs.

Drug-Related Glomerular Phenotypes: A Global Pharmacovigilance Perspective.

Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors' knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as 'potential nephrotoxins' (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as 'non-nephrotoxic', a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

Clinicopathological features and outcomes of PLA2R-related membranous nephropathy with renal glycosuria.

Membranous nephropathy (MN) is an immune complex-mediated disease. Massive proteinuria can lead to Fanconi syndrome, clinically manifesting as renal glycosuria. The prevalence and prognosis of M-type phospholipase A2 receptor (PLA2R)-related MN with renal glycosuria remain unknown. Patients diagnosed with PLA2R-related MN with renal glycosuria were reviewed, and the control group comprised patients with MN without renal glycosuria who were randomly selected at a ratio of 1:3. 50 patients diagnosed with PLA2R-related MN with renal glycosuria from January 2015 to January 2020 were included, with a prevalence of 2.3%. Compared with patients without renal glycosuria, those with renal glycosuria exhibited greater proteinuria, lower estimated glomerular filtration rate (eGFR), and higher use of diuretics, anticoagulants, antibiotics, traditional Chinese medicine, and tacrolimus within 3 months prior to renal biopsy (all p<0.05). Histologically, patients with renal glycosuria exhibited more severe pathological stages, acute/chronic tubulointerstitial lesions, and tubulointerstitial inflammation (all p<0.05). Of the 10 patients treated with rituximab (RTX), proteinuria remission was maintained in 6 (60%) patients, and urine glucose remission was achieved in 5 of these 6 patients (83.3%). Multivariate Cox regression analysis showed that renal glycosuria and age &gt;50 years were independent risk factors for end-stage renal disease (ESRD) or a 30% reduction in the eGFR in patients with PLA2R-related MN. PLA2R-related MN patients with renal glycosuria presented with more severe clinicopathological manifestations and worse prognoses. Nephrotoxic drugs should be administered rationally, and RTX should be considered as a promising treatment option.

Association between preoperative proton pump inhibitor use and postoperative acute kidney injury in patients undergoing major surgery

Background Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain. Methods This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality. Results A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04–2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03–1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55–4.85). Conclusions Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.