Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast‐Induced Nephropathy: A Failure of Academic Clinical Science

Sandilands, Euan A; Rees, J. K. H.; Raja, Khuram; Dhaun, Neeraj; Morrison, Emma; Hickson, Kirsty; Wraight, Jonathan; Gray, Tanya; Briody, Lesley; Cameron, Sharon; Thompson, Adrian; Johnston, Neil R.; Uren, Neal; Goddard, Jane; Treweeke, Andy; Rushworth, Gordon F.; Webb, David J.; Bateman, D. N.; Norrie, John; Megson, Ian L.; Eddleston, Michael

doi:10.1002/cpt.2541

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…These uncertainties must be considered when interpreting the results of this study. In the future, the new and old prophylactic effects on contrast media exposure must be extensively examined, considering the trend of N-acetylcysteine and others [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study

et al. 2023

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Background With the constant need for technique improvement for ensuring correct diagnoses and precise treatment, imaging examinations that use contrast media have become unavoidable and indispensable. However, the long-term effects of contrast media on renal function remain unclear in populations with advanced renal failure. This study aimed to examine the relationship between contrast media exposure and long-term trends in renal function in patients with renal failure. Methods This retrospective cohort study included patients with a definitive diagnosis of chronic kidney disease who visited medical institutions in Japan between April 2012 and December 2020. The cohort was divided into contrast agent therapy and non-contrast agent therapy groups. The assessment indices were the number of contrast exposures and renal function decline. Renal function decline was calculated based on observed chronic kidney disease stage trends and glomerular filtration rate correspondence tables sourced from various guidelines. A stratified analysis focusing on changes in renal function while accounting for the acceleration of chronic kidney disease progression was also performed. Results After adjusting for patient background with propensity score matching, 333 patients each were included in both groups. The observation period was 5.3 ± 2.1 and 4.9 ± 2.2 years per case in the contrast-enhanced and non-contrast-enhanced groups, respectively. The baseline estimated glomerular filtration rate at the beginning of the observation period was 55.2 ± 17.8 mL/min/1.73 m2 in the contrast-enhanced groups (P = 0.65). Although only slightly different in both groups, the glomerular filtration rate change was 1.1 ± 3.3 mL/min/1.73 m2/year in the contrast agent therapy group and tended to be higher with contrast media exposure. Stratified analysis showed that the annual glomerular filtration rate changes in patients with more contrast media exposures and altered renal function were 7.9 ± 7.1 mL/min/1.73 m2/year and 4.7 ± 3.6 mL/min/1.73 m2/year in the contrast agent therapy and non-contrast agent therapy groups, respectively (1.69 times, P < 0.05). Conclusion We were able to identify a clinical trend of successful measures for preventing adverse renal outcomes associated with contrast media exposure. However, increased frequency of contrast media exposure has a long-term effect on renal function in patients with altered it. Appropriate treatment choices related to contrast media may control chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study

et al. 2023

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“…This suggests that NAC treatment might have a therapeutic window to utilize the nephroprotective effect (216). NAC also failed to offer renal protection in patients with stage 3 chronic kidney disease at risk of contrast-induced nephropathy (217).…”

Section: Antioxidantsmentioning

confidence: 99%

NETosis: an emerging therapeutic target in renal diseases

Juha,

Molnár,

Jakus

et al. 2023

Front. Immunol.

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IntroductionNeutrophil extracellular traps (NETs) are web-like structures composed of nuclear and granular components. The primary role of NETS is to prevent the dissemination of microbes and facilitate their elimination. However, this process is accompanied by collateral proinflammatory adverse effects when the NET release becomes uncontrollable, or clearance is impaired. Although NET-induced organ damage is conducted primarily and indirectly via immune complexes and the subsequent release of cytokines, their direct effects on cells are also remarkable. NETosis plays a critical pathogenic role in several renal disorders, such as the early phase of acute tubular necrosis, anti-neutrophil cytoplasmic antibody-mediated renal vasculitis, lupus nephritis, thrombotic microangiopathies, anti-glomerular basement membrane disease, and diabetic nephropathy. Their substantial contribution in the course of these disorders makes them a desirable target in the therapeutic armamentarium. This article gives an in-depth review of the heterogeneous pathogenesis and physiological regulations of NETosis and its pivotal role in renal diseases. Based on the pathogenesis, the article also outlines the current therapeutic options and possible molecular targets in the treatment of NET-related renal disorders.MethodsWe carried out thorough literature research published in PubMed and Google Scholar, including a comprehensive review and analysis of the classification, pathomechanisms, and a broad spectrum of NET-related kidney disorders.ConclusionsNETosis plays a pivotal role in certain renal diseases. It initiates and maintains inflammatory and autoimmune disorders, thus making it a desirable target for improving patient and renal outcomes. Better understanding and clinical translation of the pathogenesis are crucial aspects to treatment, for improving patient, and renal outcomes.

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“…In this issue of Clinical Pharmacology and Therapeutics , we examine the use of N ‐acetylcysteine to prevent iodinated radiographic contrast‐induced renal dysfunction (Figure 1). Sandilands 6 describes a group of four soundly designed and well‐conducted experimental medicine studies investigating the mechanistic basis of this hypothesis. They measured pharmacokinetics of oral and i.v.…”

Section: Figurementioning

confidence: 99%

Clinical Pharmacology and the Best Use of Public Research Investment

Kraft

2022

Clin Pharma and Therapeutics

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Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast‐Induced Nephropathy: A Failure of Academic Clinical Science

Cited by 5 publications

References 39 publications

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study

NETosis: an emerging therapeutic target in renal diseases

Clinical Pharmacology and the Best Use of Public Research Investment

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