ABSTRACT
One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.
Subject(s)
Acute Kidney Injury , Nephritis, Interstitial , Renal Insufficiency, Chronic , Acute Kidney Injury/etiology , Anti-Bacterial Agents/adverse effects , Electrolytes/adverse effects , Humans , Kidney , Nephritis, Interstitial/chemically induced , Nephritis, Interstitial/complications , Renal Insufficiency, Chronic/complicationsABSTRACT
BACKGROUND: Through regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage. METHODS: Of 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR. RESULTS: The results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers. CONCLUSION: The results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04991376 . Registered on 27 July 2021.
Subject(s)
Acute Kidney Injury , Circulating MicroRNA , MicroRNAs , Sepsis , Acute Kidney Injury/complications , Adult , Anti-Bacterial Agents/therapeutic use , Creatinine , Female , Gentamicins , Humans , Interleukin-6/metabolism , Lipocalin-2 , Male , MicroRNAs/genetics , Procalcitonin , Sepsis/complications , Vancomycin/therapeutic useABSTRACT
Acute kidney injury is a common complication in critically ill patients with sepsis and/or septic shock. Further, some essential antimicrobial treatment drugs are themselves nephrotoxic. For this reason, timely diagnosis and adequate therapeutic management are paramount. Of potential acute kidney injury (AKI) biomarkers, non-protein-coding RNAs are a subject of ongoing research. This review covers the pathophysiology of vancomycin and gentamicin nephrotoxicity in particular, septic AKI and the microRNAs involved in the pathophysiology of both syndromes. PubMED, UptoDate, MEDLINE and Cochrane databases were searched, using the terms: biomarkers, acute kidney injury, antibiotic nephrotoxicity, sepsis, miRNA and nephrotoxicity. A comprehensive review describing pathophysiology and potential biomarkers of septic and toxic acute kidney injury in septic patients was conducted. In addition, five miRNAs: miR-15a-5p, miR-192-5p, miR-155-5p, miR-486-5p and miR-423-5p specific to septic and toxic acute kidney injury in septic patients, treated by nephrotoxic antibiotic agents (vancomycin and gentamicin) were identified. However, while these are at the stage of clinical testing, preclinical and clinical trials are needed before they can be considered useful biomarkers or therapeutic targets of AKI in the context of antibiotic nephrotoxicity or septic injury.
Subject(s)
Acute Kidney Injury/etiology , Anti-Bacterial Agents/adverse effects , Sepsis/complications , Sepsis/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Acute Kidney Injury/physiopathology , Animals , Anti-Bacterial Agents/therapeutic use , Biomarkers/analysis , Gentamicins/adverse effects , Gentamicins/therapeutic use , Humans , Kidney/drug effects , Kidney/physiopathology , MicroRNAs/analysis , Sepsis/diagnosis , Sepsis/physiopathology , Vancomycin/adverse effects , Vancomycin/therapeutic useABSTRACT
The presented case demonstrates that acute lead poisoning may occur due to just short-term exposure to a mixture of lead-containing dust and ammunition. Such exposure may result in high blood lead levels persisting for years in the absence of any symptoms. A middle-aged male with a history of an approximately 7-day cleanup of an old recreational firing range with large ammunition and dust deposits presented to an emergency department with abdominal pain, dyspnea, fatigue and impaired cognitive function. Given his occupational history, specific tests were performed that showed high lead concentrations in both blood and urine. The patient was diagnosed with acute lead poisoning. He was started on chelation therapy that improved both clinical and laboratory parameters. Over a subsequent nearly 3-year follow-up, the patient's blood lead levels fluctuated and continued to be increased. Given the absence of other sources of lead exposure, these were likely due to the formation of bone deposits. Med Pr. 2020;71(3):375-9.
