Pulmonary congestion and systemic congestion in hemodialysis: dynamics and correlations.

Introduction: Systemic congestion and pulmonary congestion (PC) are common in hemodialysis (HD) patients. However, the relationship between these two entities is not quite clear. We study this relationship and attempt to uncover the factors that may affect it considering different inter-dialytic intervals. Methods: A prospective pilot observational and interventional study including 18 HD patients was conducted. The following were obtained: i) B-line score (BLS) by lung ultrasound (LUS) (reflecting significant pulmonary congestion if BLS > 5), ii) echocardiography, iii) bioelectrical impedance analysis (BIA) (reflecting global volume status), and iv) inferior vena cava (IVC) dynamics (reflecting systemic congestion) before and after the first two consecutive HD sessions of the week, with different inter-dialytic intervals (68 hours and 44 hours). Serum N-terminal pro-brain natriuretic peptide type B (NT-proBNP) levels were obtained before each session. Then, patients were randomized into two groups: the active group, where dry weight was reduced according to BLS + standard of care, and the control group, where dry weight was modified according to standard of care. All the measures were repeated on day 30. Results: We found no correlation between pulmonary congestion represented by BLS and IVC dimensions and dynamics reflecting systemic congestion, independent of different inter-dialytic intervals. Pulmonary congestion was quite prevalent, as mean pre- and post-dialysis BLSs were quite elevated (16 ± 5.53 and 15.3 ± 6.63, respectively) in the first session compared with the second session (16.3 ± 5.26 and 13.6 ± 5.83, respectively). Systolic (left ventricular ejection fraction) and diastolic cardiac function (e/è ratio) parameters from one side and pulmonary congestion (BLS) from the other were not always correlated. BLS was correlated to e/è ratio before HD (session 1) (R 2 = 0.476, p = 0.002) and after HD (session 2) (R 2 = 0.193, p = 0.034). Pulmonary congestion reflected by BLS was correlated to the global volume state reflected by BIA only in the second HD session (HD2) (R 2 = 0.374, p = 0.007). NT-proBNP levels and BLS were correlated before both sessions (R 2 = 0.421, p = 0.004, and R 2 = 0.505, p = 0.001, respectively). Systemic congestion was quite prevalent, as mean pre- and post-dialysis IVC dimensions and dynamics were quite elevated in both sessions, with a higher level of systemic congestion in the first HD session (diameter and collapsibility of 2.1 cm and 23%, and 2.01 cm and 19%, respectively) compared with the second session (1.98 cm and 17.5%, and 1.9 cm and 22%, respectively) without reaching statistical significance. IVC dimensions and global volume status measured by BIA were correlated in the second dialysis session (R 2 = 0.260, p = 0.031). No correlation was found between IVC dimensions and diastolic cardiac function (e/è ratio) parameters or with NT-proBNP levels. On day 30, BLS was significantly reduced in the active group, whereas no difference was found in the control group. However, no real impact was observed on IVC dimensions and dynamics or in total volume status by BIA. Conclusion: Pulmonary congestion is common in HD patients even after reaching their dry weight at the end of two consecutive sessions, and it is not correlated to systemic congestion, suggesting a complex multifactorial pathophysiology origin. Global volume status reflected by BIA and cardiac function are not always related to either systemic congestion represented by IVC dimensions or pulmonary congestion represented by BLS. Fluid redistribution anomalies may allow pulmonary congestion accumulation independently from systemic congestion and global volume status (non-cardiogenic pulmonary congestion). We recommend a personalised approach when managing HD patients by integrating systemic and pulmonary congestion parameters. Dry weight modification guided by repeat LUS may safely reduce pulmonary congestion. However, no impact was observed on systemic congestion or global volume status.

Antiphospholipid Antibodies Associated with Native Arteriovenous Fistula Complications in Hemodialysis Patients: A Comprehensive Review of the Literature.

Antiphospholipid antibody (aPL)-persistent positivity is frequent in hemodialysis (HD) patients. Native arteriovenous fistula (AVF) complications such as stenosis and thrombosis are among the most important causes of morbidity and mortality in hemodialysis patients. The association between aPL positivity and AVF thrombosis seems to now be well established. However, whether aPL positivity is associated with other AVF complications, such as maturation failure or stenosis, is not well known. Given the significant impact of AVF failure on patient's prognosis, it is of interest to further investigate this particular point in order to improve prevention, surveillance and treatment, and, ultimately, the patient's outcome. This literature review aims to report the recent literature on aPL-associated native AVF complications.

Longitudinal Follow-Up of Serum and Urine Biomarkers Indicative of COVID-19-Associated Acute Kidney Injury: Diagnostic and Prognostic Impacts.

In patients hospitalized for severe COVID-19, the incidence of acute kidney injury (AKI) is approximately 40%. To predict and understand the implications of this complication, various blood and urine biomarkers have been proposed, including neutrophil gelatinase-associated lipocalin (NGAL), chemokine (C-C motif) ligand 14 (CCL14), cystatin C, leucine aminopeptidase (LAP), and soluble urokinase plasminogen activator (suPAR). This study, conducted between mid-January and early May 2021, aimed to assess the diagnostic and prognostic capabilities of these biomarkers in a cohort of COVID-19 patients monitored during the initial two weeks of hospitalization. Among the 116 patients included in this study, 48 developed AKI within the first three days of hospitalization (41%), with 29 requiring intensive care unit (ICU) admission, and the overall mortality rate was 18%. AKI patients exhibited a statistically significant increase in urinary LAP levels, indicating acute tubular injury as a potential mechanism underlying COVID-19-related renal damage. Conversely, urinary NGAL and CCL-14 excretion rates did not differ significantly between the AKI and non-AKI groups. Importantly, elevated plasma suPAR and cystatin C levels upon admission persisted throughout the first week of hospitalization and were associated with unfavorable outcomes, such as prolonged ICU stays and increased mortality, irrespective of AKI development. In conclusion, this study underscores the early predictive value of urinary LAP levels in identifying acute tubular injury in COVID-19-induced AKI. Moreover, elevated plasma suPAR and cystatin C levels serve as valuable prognostic markers, offering insights into the short-term morbidity and mortality risks among COVID-19 patients, regardless of AKI occurrence. These findings shed light on the complex interplay between COVID-19, renal injury, and biomarkers with diagnostic and prognostic potential.

Multiple Complications of Crohn's Disease and the Need for Early and Continuous Multidisciplinary Undertaking.

Crohn's disease is an inflammatory disease that typically affects the bowels but can also have many different extraintestinal manifestations. One of those complications is immunoglobulin A nephropathy (IgAN), which is one of the most encountered renal lesions in the setting of Crohn's disease. Another point of focus for Crohn's patients is the risk of cancer, with a higher risk of colorectal cancer but also extraintestinal neoplasia such as hepatobiliary, hematological, and urinary tract neoplasia. We present the case of a young patient suffering from long-term Crohn's disease and subsequent IgAN leading to end-stage kidney disease and hemodialysis. The patient was diagnosed young and had undergone multiple surgeries and different treatments in various countries. He then presented in our center already with advanced chronic renal failure from IgAN that was unknown due to poor multidisciplinary follow-up. Shortly after starting hemodialysis, he developed a large abdominal mass, first thought to result from Crohn's-related fistula. This mass turned out to be a urachal adenocarcinoma, a rare type of bladder cancer with an especially poor prognosis. It is not known whether this type of cancer is associated with either Crohn's disease or IgAN, and no such association has been previously described. The treatment of urachal cancer usually relies on surgery, with the addition of chemotherapy in some cases. Unfortunately for our patient, his case was already so advanced at the moment of diagnosis that he was excluded from curative treatment and quickly passed away thereafter. This case illustrates many important aspects of the rigorous follow-up that is needed for Crohn's patients, with regular check-ups, screening investigations, and the need for multidisciplinary evaluation. Furthermore, it describes the development of a rare type of cancer in the setting of Crohn's disease and IgAN, with no prior established link between these different pathologies.

Evaluation of Transplant Suitability in a Patient with Previous Colorectal Cancer and Subsequent Radiation Cystitis: Insights from a Complicated Case.

Assessing transplant suitability can be a meticulous process, involving multiple investigations and various specialties. This process is well described in the latest KDIGO guidelines. We recently asked ourselves if those guidelines are still relevant to current clinical practice given the rapid evolution of modern medicine, especially in the field of oncology. We present the complicated case of a 60-year-old woman with ESKD (end-stage kidney disease) and a prior history of cancer, with secondary urological complications, to illustrate different interesting considerations for KT (kidney transplant). Our patient was diagnosed with rectal cancer at the age of 46, for which she was treated with surgery and radiotherapy before developing chronic radiation cystitis. This was followed by repeated urinary tract infections and secondary nephrolithiasis, ultimately leading to severe bilateral hydronephrosis and obstructive ESKD. We know that the type of cancer and its characteristics should be evaluated in detail, and we should offer patient-tailored recommendations after a multidisciplinary evaluation. In our case, the prior rectal cancer is not to be feared because curative treatment has been achieved and the patient has been cancer-free for 14 years, knowing that this type of cancer is not at high risk of recurrence after transplantation. The frail urological anatomy, however, represents a bigger challenge. Not only does it complicate the technical feasibility of KT but it also increases the risk of complications and graft failure. It is difficult to clearly determine KT possibility when considering it in such patients. What is clear on the other hand is that such a decision should be taken considering the choice of the patient and the involved physicians. We should also consider the potential benefits and risks of KT in order to make an informed decision.

Native Mitral Valve Endocarditis Caused by a Non-HACEK Gram-Negative Pathogen in a Hemodialysis Patient.

Infective endocarditis (IE) due to non-HACEK (species other than Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia accounts for less than 2% of all IE cases but is proven to be associated with higher mortality, even more so in hemodialysis (HD) patients. Few data are available in the literature concerning non-HACEK Gram-negative (GN) IE in this immunocompromised population with multiple comorbidities. We report the atypical clinical presentation of an elderly HD patient diagnosed with a non-HACEK GN IE, namely E. coli, successfully treated with intravenous (IV) antibiotics. The objective of this case study and related literature was to highlight the limited applicability of the modified Duke criteria in the HD population, as well as the frailty of HD patients that increases their susceptibility to IE due to unexpected microorganisms that could have fatal consequences. The need for a multidisciplinary approach of an IE in HD patients is therefore imperative.

Jejunal perforation secondary to blind insertion of peritoneal dialysis catheter: a case report and review of literature.

BACKGROUND: Peritoneal dialysis (PD) depends upon a functioning and durable access to the peritoneal cavity. Many techniques exist to insert a peritoneal catheter, showing similar outcomes and benefits. Blind percutaneous insertion represents a bedside intervention predominantly performed by nephrologists requiring only local anesthesia, sedation and minimal transcutaneous access. Although current guidelines recommend insertion techniques allowing visualization of the peritoneal cavity, the blind percutaneous approach is still widely used and has been proven safe and effective to bring durable peritoneal dialysis access. Herein, we described a rare case of jejunal perforation secondary to blind PD catheter placement, and conduct a review of the current medical literature describing early bowel perforations secondary to PD catheter placement, gathering descriptions of symptomatology and outcomes and their relations to the insertion technique. CLINICAL PRESENTATION: We herein describe the case of a 48 year-old patient with a history of appendectomy who suffered from triple jejunal perforation after blind percutaneous insertion and subsequent embedment of his peritoneal catheter. Accurate diagnosis was made 1 month after insertion due to atypical clinical presentation and because physicians had no access to the peritoneal cavity after catheter embedment. After surgical repair and broad-spectrum antibiotics, the patient was switched to HD. CONCLUSION: Early catheter-related visceral injury is a rare, yet threatening condition that is almost always causing a switch to hemodialysis or death. Our review highlights that laparoscopic catheter placement might bring better outcomes if perforation occurs, as it allows immediate diagnosis and treatment. On the contrary, catheter embedment may delay clinical diagnosis and therefore bring worse outcomes.

Assessment of the Cytotoxicity, Mutagenicity, and Genotoxicity of Two Traditional Chinese Herbs: Aristolochia baetica and Magnolia officinalis.

Herbal remedies used in traditional medicine often contain several compounds combined in order to potentiate their own intrinsic properties. However, herbs can sometimes cause serious health troubles. In Belgium, patients who developed severe aristolochic acid nephropathy ingested slimming pills containing root extracts of an Aristolochia species, as well as the bark of Magnolia officinalis. The goal of the study was to evaluate, on a human renal cell line, Aristolochia and Magnolia extracts for their cytotoxicity by a resazurin cell viability assay, and their genotoxicity by immunodetection and quantification of the phosphorylated histone γ-H2AX. The present study also sought to assess the mutagenicity of these extracts, employing an OECD recognized test, the Ames test, using four Salmonella typhimurium strains with and without a microsomial fraction. Based on our results, it has been demonstrated that the Aristolochia-Magnolia combination (aqueous extracts) was more genotoxic to human kidney cells, and that this combination (aqueous and methanolic extracts) was more cytotoxic to human kidney cells after 24 and 48 h. Interestingly, it has also been shown that the Aristolochia-Magnolia combination (aqueous extracts) was mutagenic with a TA98 Salmonella typhimurium strain in the presence of a microsomial liver S9 fraction. This mutagenic effect appears to be dose-dependent.

Undetected Iatrogenic Drug-Induced Complications in a Hemodialyzed Anuric Patient: A Case Report and Review of the Literature.

Anuric hemodialyzed end-stage renal disease patients are prone to multiple complications and comorbidities and are therefore often treated with various medications. Adverse drug reactions and risk factors leading to them can be difficult to discern in such polymedicated patients. Most problems regarding low phosphate levels are frequently underdiagnosed in clinical practice and sometimes overlooked in these regularly hyperphosphatemic patients. Hemodialysis vascular accesses are frequently subject to infections and therefore require adapted antibiotic treatments. We report a case of an occult severe multifactorial hypophosphatemia in an anuric hemodialyzed patient with multiple comorbidities who required two hospitalizations for encephalopathy, seizures, and cardiac failure. Retrospective analysis of the medical record revealed several underlying causes of hypophosphatemia, as well as undetected risk factors for adverse drug reactions related to cephalosporins. A global approach to these concerns in routine clinical practice would raise awareness of often disregarded issues related to hypophosphatemia and drug prescription in these patients.

[Negative impact of COVID-19 pandemic on peritonitis rate in peritoneal dialysis patients: Pleading for a continuous educational training]. / Conséquences de la pandémie de COVID-19 sur le taux de péritonites de dialyse péritonéale : plaidoyer pour une formation continue ininterrompue.

BACKGROUND: Peritonitis is a common complication of chronic peritoneal dialysis treatment contributing to both technique failure and/or death. Little is effectively known about the actual benefits of a continuous training program on peritonitis rates. In the present study, we measured the impact of our patients' training protocol on peritonitis rates. We further studied which consequences the COVID-related disruption of our follow-up program had on peritonitis rates. METHODS: We present our yearly peritonitis rates since our patients' training and retraining program was implemented in 2010. We then focused our study on three consecutive years: 2019, 2020 (emergence of COVID-19), and 2021, collecting microbiological data from each peritonitis episode. Statistical analysis were used to corroborate our findings. RESULTS: Since 2010, peritonitis rates declined linearly (R2=0,6556; df=8; P<0.01) until its nadir in 2019 with 4 peritonitis episodes. The majority of infections were then treated in the outpatient Clinic. In 2020, our continuous technique evaluation decreased by 51% and 28 peritonitis episodes occurred, 47% secondary to strict cutaneous bacteria's, and 31% gastro-intestinal, irrespective of patients' experience or peritoneal dialysis modality. The hospitalization rate reached 71%. Having restored our protocol, we decreased peritonitis rates by 50% in 2021. CONCLUSIONS: Risk factors for peritonitis are identifiable and modifiable and require sustained intervention, continuous visual monitoring and training. These interventions significantly reduce peritonitis rates. Any brief interruption to patients' technique evaluation may elevate peritonitis rates significantly.

Nephroprotective Effects of Two Ganoderma Species Methanolic Extracts in an In Vitro Model of Cisplatin Induced Tubulotoxicity.

Although cisplatin is used as a first-line therapy in many cancers, its nephrotoxicity remains a real problem. Acute kidney injuries induced by cisplatin can cause proximal tubular necrosis, possibly leading to interstitial fibrosis, chronic dysfunction, and finally to a cessation of chemotherapy. There are only a few nephroprotective actions that can help reduce cisplatin nephrotoxicity. This study aims to identify new prophylactic properties with respect to medicinal mushrooms. Among five Ganoderma species, the methanolic extracts of Ganoderma tuberculosum Murill., Ganoderma parvigibbosum Welti & Courtec. (10 µg/mL), and their association (5 + 5 µg/mL) were selected to study respective in vitro effects on human proximal tubular cells (HK-2) intoxicated by cisplatin. Measurements were performed after a pretreatment of 1 h with the extracts before adding cisplatin (20 µM). A viability assay, antioxidant activity, intracytoplasmic ß-catenin, calcium, caspase-3, p53, cytochrome C, IL-6, NFκB, membranous KIM-1, and ROS overproduction were studied. Tests showed that both methanolic extracts and their association prevented a loss of viability, apoptosis, and its signaling pathway. G. parvigibbosum and the association prevented an increase in intracytoplasmic ß-catenin. G. parvigibbosum prevented ROS overproduction and exhibited scavenger activity. None of the extracts could interfere with pro-inflammatory markers or calcium homeostasis. Our in vitro data demonstrate that these mushroom extracts have interesting nephroprotective properties. Finally, the chemical content was investigated through a phytochemical screening, and the determination of the total phenolic and triterpenoid content. Further studies about the chemical composition need to be conducted.

Iatrogenic Infective Endocarditis in Hemodialysis Patients: A Case Report and Review of the Literature.

Foreign bodies such as implanted cardiac devices are susceptible to infections and may be involved in infective endocarditis. Exposure to pathogens, by frequent use of intravascular accesses for hemodialysis (i.e., catheters or fistulas), combined with high rates of degenerative heart valve diseases in hemodialysis patients, both favor the development of infective endocarditis in this population. The mitral and aortic valves are predominantly implicated in endocardial infections. The involvement of both mitral and tricuspid valves is rare in the general population but can occur in hemodialysis patients with implanted cardiac devices. Infective endocarditis is associated with high morbidity and mortality rates among hemodialysis patients, mostly because of the complications of septic emboli. Prevention, prophylaxis, and early diagnosis of endocarditis can be lifesaving in this fragile population. We report a case of right and left heart methicillin-sensitive Staphylococcus aureus endocarditis with cerebral septic emboli in an elderly hemodialysis patient carrier of an arteriovenous fistula and an ipsilateral nonleadless pacemaker.

Clinical management of a granulomatous tubulointerstitial nephritis associated with a bilateral granulomatous anterior uveitis: A challenging case report and review of the literature.

Acute granulomatous tubulointerstitial nephritis (GTIN) is a rare finding in renal biopsy. Differential diagnosis is facilitated when GTIN is associated with granulomatous bilateral anterior uveitis (GBAU). Nevertheless, differentiation between a rare form of granulomatous tubulointerstitial nephritis and uveitis syndrome (TINU) and sarcoidosis can be challenging. We report a case of biopsy-proven GTIN with concomitant GBAU, leading to a dead-end diagnosis. We discuss workup and propose a diagnostic algorithm based on a literature review. We also report a successful treatment of ophthalmologic and renal relapse using mycophenolate mofetil.

Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition.

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFß in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.

Aristolochic acid I as an emerging biogenic contaminant involved in chronic kidney diseases: A comprehensive review on exposure pathways, environmental health issues and future challenges.

Described in the 1950s, Balkan Endemic Nephropathy (BEN) has been recognized as a chronic kidney disease (CKD) with clinical peculiarities and multiple etiological factors. Environmental contaminants - aromatic compounds, mycotoxins and phytotoxins like aristolochic acids (AAs) - polluting food and drinking water sources, were incriminated in BEN, due to their nephrotoxic and carcinogenic properties. The implication of AAs in BEN etiology is currently a highly debated topic due to the fact that they are found within the Aristolochiaceae plants family, used around the globe as traditional medicine and they were also incriminated in Aristolochic Acid Nephropathy (AAN). Exposure pathways have been investigated, but it is unclear to what extent AAs are acting alone or in synergy with other cofactors (environmental, genetics) in triggering kidney damage. Experimental studies strengthen the hypothesis that AAI, the most studied compound in the AAs class, is a significant environmental contaminant and a most important causative factor of BEN. The aim of this review is to compile information about the natural exposure pathways to AAI, via traditional medicinal plants, soil, crop plants, water, food, air. Data that either supports or contradicts the AAI theory concerning BEN etiology was consolidated and available solutions to reduce human exposure were discussed. Because AAI is a phytotoxin with physicochemical properties that allow its transportation in environmental matrices from different types of areas (endemic, nonendemic), and induce CKDs (BEN, AAN) and urinary cancers through bioaccumulation, this review aims to shed a new light on this compound as a biogenic emerging pollutant.

Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells.

Aristolochic acids (AAs) are powerful nephrotoxins that cause severe tubulointerstitial fibrosis. The biopsy-proven peritubular capillary rarefaction may worsen the progression of renal lesions via tissue hypoxia. As we previously observed the overproduction of reactive oxygen species (ROS) by cultured endothelial cells exposed to AA, we here investigated in vitro AA-induced metabolic changes by 1H-NMR spectroscopy on intracellular medium and cell extracts. We also tested the effects of nebivolol (NEB), a ß-blocker agent exhibiting antioxidant properties. After 24 h of AA exposure, significantly reduced cell viability and intracellular ROS overproduction were observed in EAhy926 cells; both effects were counteracted by NEB pretreatment. After 48 h of exposure to AA, the most prominent metabolite changes were significant decreases in arginine, glutamate, glutamine and glutathione levels, along with a significant increase in the aspartate, glycerophosphocholine and UDP-N-acetylglucosamine contents. NEB pretreatment slightly inhibited the changes in glutathione and glycerophosphocholine. In the supernatants from exposed cells, a decrease in lactate and glutamate levels, together with an increase in glucose concentration, was found. The AA-induced reduction in glutamate was significantly inhibited by NEB. These findings confirm the involvement of oxidative stress in AA toxicity for endothelial cells and the potential benefit of NEB in preventing endothelial injury.

Characterization of cytotoxic effects of aristolochic acids on the vascular endothelium.

Aristolochic acid nephropathy (AAN) is characterized by interstitial fibrosis, proximal tubular atrophy, and hypoxia. A correlation between a reduced peritubular capillary density and the severity of fibrosis has been demonstrated. As calcium, redox and energetic homeostasis are crucial in maintaining endothelial cell function and survival, we aimed to investigate AA-induced disturbances involved in endothelial cell injury. Our results showed a cytotoxic effect of AA on EAhy926 endothelial cells. Exposure of aortic rings to AA impaired vascular relaxation to Acetylcholine (ACh). Increased levels of intracellular reactive oxygen species (ROS) were observed in cells exposed to AA. Pre-treatment with antioxidant N-acetyl cysteine inhibited AA-induced cell death. Superoxide dismutase resulted in restoring ACh-induced relaxation. An increase in intracellular calcium level ([Ca2+]i) was observed on endothelial cells. Calcium chelators BAPTA-AM or APB, a specific inhibitor of IP3R, improved cell viability. Moreover, AA exposure led to reduced AMP-activated protein kinase (AMPK) expression. AICAR, an activator of AMPK, improved the viability of AA-intoxicated cells and inhibited the rise of cytosolic [Ca2+]i levels. This study provides evidence that AA exposure increases ROS generation, disrupts calcium homeostasis and decreases AMPK activity. It also suggests that significant damage observed in endothelial cells may enhance microcirculation defects, worsening hypoxia and tubulointerstitial lesions.