Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study

McWilliam, Stephen; Antoine, Daniel J.; Sabbisetti, Venkata; Turner, Mark A.; Farragher, Tracey; Bonventre, Joseph V.; Park, B. Kevin; Smyth, Rosalind L; Pirmohamed, Munir

doi:10.1371/journal.pone.0043809

Cited by 74 publications

(72 citation statements)

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“…It is well defined that many drugs, such as the chemotherapeutic drug (cisplatin) and aminoglycoside antibiotics are able to cause nephrotoxicity [54-56]. …”

Section: Resultsmentioning

confidence: 99%

An Overview on Renoprotective Effects of Thymoquinone

et al. 2018

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Background: Kidneys as vital organs remove waste material from blood. Additionally, they may also have a role in the electrolyte balance, regulation of blood pressure, and red blood cell genesis. Kidney diseases may be caused by several factors such as ischemia/reperfusion injury, diabetes, and nephrotoxic agents. Oxidative stress and inflammation are involved in the pathogenesis and progression of kidney diseases. Traditionally, natural antioxidants are used for treatment of renal failure in various countries. Summary: People usually select natural antioxidants since they have an opinion that herbal medicine has not any important side effects. Nigella sativa is a flavoring herb that is widely used as a condiment and as a remedy for many disorders. Thymoquinone (TQ), the most important component of black seeds, mainly oil, is considered as an active agent responsible for a lot of the seed’s useful effects. This review describes the protective roles and related mechanisms of TQ against renal disorders. The search terms, including TQ, antioxidant, renal ischemia-reperfusion, diabetic nephropathy, and nephrotoxic agent were searched in scientific databases. TQ showed anti-inflammatory and antioxidant properties in animal and in vitro models of several renal diseases caused by inflammation and oxidative stress. Key Messages: Experimental studies have shown beneficial effects of TQ against renal diseases; however, well-designed clinical trials in humans are required to confirm these effects.

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“…It is well defined that many drugs, such as the chemotherapeutic drug (cisplatin) and aminoglycoside antibiotics are able to cause nephrotoxicity [54-56]. …”

Section: Resultsmentioning

confidence: 99%

An Overview on Renoprotective Effects of Thymoquinone

et al. 2018

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“…131 Identification and validation of biomarkers would allow earlier detection of AKI in premature infants and permit generalizability between single-center studies. [132][133][134] Biomarkers including urine cystatin C, uromodulin, epithelial growth factor, neutrophil gelatinase-associated lipocalin, and osteopontin predict AKI in specific neonatal populations. 135,136 …”

Section: Acute Kidney Injurymentioning

confidence: 99%

Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

2013

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Thanks to remarkable advances in neonatal intensive care, infants who once had little chance for survival can now enter adulthood. Yet the consequences of premature birth or low birth weight (LBW) on nephrogenesis, final nephron number, and long-term kidney function are unclear. This review focuses on the theory, experimental evidence, and observational data that suggest an increased risk of chronic kidney disease (CKD) for infants born prematurely. Many premature and LBW infants begin life with an incomplete complement of immature nephrons. They are then exposed to a variety of external stressors that can hinder ongoing kidney development or cause additional nephron loss such as hemodynamic alterations, nephrotoxic medications, infections, and suboptimal nutrition. Acute kidney injury, in particular, may be a significant risk factor for the development of CKD. According to Brenner' s hypothesis, patients with decreased nephron number develop hyperfiltration that results in sodium retention, hypertension, nephron loss, and CKD due to secondary focal segmental glomerulosclerosis. Because the risk of CKD in premature and LBW infants has not been accurately determined, there are no evidence-based recommendations for screening or management. Yet with the first generation of infants from the surfactant era only now reaching adulthood, it is possible that there is already an unrecognized epidemic of CKD. We suggest individualized, risk-based assessments of premature and LBW infants due to the increased risk of CKD and call for additional research into the long-term risk for CKD these infants face.

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“…Furthermore, immaturity can result in an altered risk of drug toxicity, even a decreased risk. To illustrate this, neonates appear to be less susceptible to renal toxicity induced by aminoglycosides compared to children and adults, due to reduced intracellular accumulation of these compounds in the renal tubular cells [24,25]. Similar to the expansion of biomarker research in human (adult) medicine, there is an active search for robust biomarkers to evaluate interventions in neonates and infants.…”

Section: Introductionmentioning

confidence: 99%