Optimising the use of medicines to reduce acute kidney injury in children and babies

Oni, Louise; Hawcutt, Daniel B; Turner, Mark A.; Beresford, MW; McWilliam, Stephen; Barton, Christopher; Park, BK; Murray, Patricia; Wilm, Bettina; Copple, Ian M.; Floyd, Rachel V.; Peak, Matthew; Sharma, Arpita; Antoine, Dan

doi:10.1016/j.pharmthera.2017.02.018

Cited by 8 publications

(8 citation statements)

References 83 publications

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“…The features of TILs differ among diseases. Drug-induced acute kidney injury (AKI), caused by antibiotics or anticancer drugs, is characterized by severe injuries of proximal tubules (PTs) ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney

et al. 2017

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IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36α+ DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36α receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36α stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36α-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36α-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36α overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36α may be a novel kidney injury marker useful for evaluating DT damages.

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Section: Introductionmentioning

confidence: 99%

IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney

et al. 2017

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“…Acute kidney failure may already occur in children after short-term drug use (~ 5 days), especially when predisposing risk factors such as dehydration, prediagnosed kidney disease (renal transplantation), and concomitant therapy with other nephrotoxic drugs are present [185,186]. Kidney damage through NSAIDs occurs through two different mechanisms, which include (1) altered renal hemodynamics by vasoconstriction of the afferent glomerular arteriole leading to reduced renal perfusion, local hypoxia and acute tubular necrosis, and (2) tubular interstitial nephritis mediated by locally increased production of leukotrienes [187]. AKI in children occurs more frequently in critically ill children (27%) rather than in non-critically ill children (5%), and critically ill children are also at a higher risk of drug-induced AKI [188][189][190].…”

Section: Renal Safetymentioning

confidence: 99%

Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years

Ziesenitz

Welzel²,

Dyk³

et al. 2022

Pediatr Drugs

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Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain. NSAIDs are also the main pillars of anti-inflammatory treatment, such as in pediatric inflammatory rheumatic diseases. Limited data are available on the safety of most NSAIDs in infants. Adverse drug reactions may be renal, gastrointestinal, hematological, or immunologic. Since NSAIDs are among the most frequently used drugs in the pediatric population, safety and efficacy studies can be performed as part of normal clinical routine, even in young infants. Available data sources, such as (electronic) medical records, should be used for safety and efficacy analyses. On a larger scale, existing data sources, e.g. adverse drug reaction programs/networks, spontaneous national reporting systems, and electronic medical records should be assessed with childspecific methods in order to detect safety signals pertinent to certain pediatric age groups or disease entities. To improve the safety of NSAIDs in infants, treatment needs to be initiated with the lowest age-appropriate or weight-based dose. Duration of treatment and amount of drug used should be regularly evaluated and maximum dose limits and other recommendations by the manufacturer or expert committees should be followed. Treatment for non-chronic conditions such as fever and acute (postoperative) pain should be kept as short as possible. Patients with chronic conditions should be regularly monitored for possible adverse effects of NSAIDs.

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“…The glomeruli tend to be primarily damaged in focal segmental glomerulosclerosis (FSGS) and in the various types of glomerulonephritis due to genetic mutations or immunological changes and secondarily damaged in systemic diseases such as numerous infectious diseases or autoimmune diseases including systemic lupus erythematosus (SLE; https://www.kidney.org/). On the other hand, the tubulointerstitium tends to be damaged due to the use of antibiotics or anticancer drugs, which usually involve injuries of PTs 4 . Furthermore, the localization of lesions in hereditary kidney diseases depends on the kind of mutated genes.…”

Section: Mirnas In the Kidneysmentioning

confidence: 99%

MicroRNAs associated with the development of kidney diseases in humans and animals

Ichii

Horino

2018

J Toxicol Pathol

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Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18–25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing. Particularly, miR-21 seems to be strongly associated with renal pathogenesis both in the glomerulus and tubulointerstitium. Furthermore, abundant evidence has been gathered showing the involvement of miRNAs in renal fibrosis. Because of the complex morphofunctional organization of the mammalian kidneys, it is crucial both to determine the exact localization of the kidney cells that express the miRNAs, which has been addressed mainly using in situ hybridization methods, and to identify precisely which mRNAs are bound and degraded by these miRNAs, which has been studied mostly through in vitro analysis. To discover novel biomarker candidates, miRNA levels in urine supernatant, sediment, and exosomal fraction were comprehensively investigated in different types of kidney disease, including drug-induced AKI, ischemia-induced AKI, diabetic nephropathy, lupus nephritis, and IgA nephropathy. Recent studies also demonstrated the therapeutic effect of miRNA and/or anti-miRNA administrations. The intent of this review is to illustrate the state-of-the-art research in the field of miRNAs associated with renal pathogenesis, especially focusing on AKI and CKD in humans and animal models.

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Optimising the use of medicines to reduce acute kidney injury in children and babies

Cited by 8 publications

References 83 publications

IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney

IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney

Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years

MicroRNAs associated with the development of kidney diseases in humans and animals

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