Concise review: Current and emerging biomarkers of nephrotoxicity

Weber, Elijah; Himmelfarb, Jonathan; Kelly, Edward J.

doi:10.1016/j.cotox.2017.03.002

Cited by 19 publications

(14 citation statements)

References 47 publications

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“…Also, novel biomarkers for nephrotoxicity including kidney‐specific proteins or urinary micro RNA are being researched. These may provide advantages over the classic criteria for acute kidney injury such as elevated serum creatinine in association with oliguria and increased blood urea nitrogen, which are not sensitive enough to detect early signs of kidney injury and often indicate only irreversible kidney damage 25 …”

Section: Clinical Pharmacology Of Antibioticsmentioning

confidence: 99%

“…These may provide advantages over the classic criteria for acute kidney injury such as elevated serum creatinine in association with oliguria and increased blood urea nitrogen, which are not sensitive enough to detect early signs of kidney injury and often indicate only irreversible kidney damage. 25 Under which conditions is TDM with individualized dosing of antibiotics useful?…”

Section: Biomarkers: Quantitative Information About Treatment Response and Toxicitymentioning

confidence: 99%

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From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Wicha

Märtson

Nielsen

et al. 2021

Clin Pharma and Therapeutics

169

159

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(ISAP), the PK/PD study group of the European Society of Clinical Microbiology, Infectious Diseases (EPASG) Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have evolved as important tools to inform rational dosing of antibiotics in individual patients with infections. In particular, critically ill patients display altered, highly variable pharmacokinetics and often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used to individualize dosing in this patient group for many years. More recently, there has been increasing research on the use of MIPD software to streamline the TDM process, which can increase the flexibility and precision of dose individualization but also requires adequate model validation and re-evaluation of existing workflows. In parallel, new minimally invasive and noninvasive technologies such as microneedle-based sensors are being developed, which-together with MIPD software-have the potential to revolutionize how patients are dosed with antibiotics. Nonetheless, carefully designed clinical trials to evaluate the benefit of TDM and MIPD approaches are still sparse, but are critically needed to justify the implementation of TDM and MIPD in clinical practice. The present review summarizes the clinical pharmacology of antibiotics, conventional TDM and MIPD approaches, and evidence of the value of TDM/MIPD for aminoglycosides, beta-lactams, glycopeptides, and linezolid, for which precision dosing approaches have been recommended.

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Section: Clinical Pharmacology Of Antibioticsmentioning

confidence: 99%

Section: Biomarkers: Quantitative Information About Treatment Response and Toxicitymentioning

confidence: 99%

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

Wicha

Märtson

Nielsen

et al. 2021

Clin Pharma and Therapeutics

169

159

View full text Add to dashboard Cite

show abstract

“…One of the most promising and intensively investigated approaches is the search for specific biomarkers for early detection of kidney injury. Recently, the FDA and the European Medicines Agency have approved biomarkers for kidney injury in humans who have fulfilled the above criteria including kidney injury molecule‐1 (Kim‐1), cystatin C, α‐glutathione S‐transferase (GST), neutrophil gelatinase‐associated lipocalin, clusterin, osteopontin, and albumin 86,87 . These biomarkers are likely to be superior to sCr because their levels are affected much earlier than those of sCr, so early detection of AKI or nephrotoxicity is possible with them.…”

Section: Management Prevention Diagnosis and Challengesmentioning

confidence: 99%

A Review on Drug‐Induced Nephrotoxicity: Pathophysiological Mechanisms, Drug Classes, Clinical Management, and Recent Advances in Mathematical Modeling and Simulation Approaches

Mody

Ramakrishnan

Chaar

et al. 2020

Clinical Pharm in Drug Dev

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A variety of marketed drugs belonging to various therapeutic classes are known to cause nephrotoxicity. Nephrotoxicity can manifest itself in several forms depending on the specific site involved as well as the underlying pathophysiological mechanisms. As they often coexist with other pathophysiological conditions, the steps that can be taken to treat them are often limited. Thus, drug-induced nephrotoxicity remains a major clinical challenge. Prior knowledge of risk factors associated with special patient populations and specific classes of drugs, combined with early diagnosis, therapeutic drug monitoring with dose adjustments, as well as timely prospective treatments are essential to prevent and manage them better. Most incident drug-induced renal toxicity is reversible only if diagnosed at an early stage and treated promptly. Hence, diagnosis at an early stage is the need of the hour to counter it. Significant recent advances in the identification of novel early biomarkers of nephrotoxicity are not beyond limitations. In such a scenario, mathematical modeling and simulation (M&S) approaches may help to better understand and predict toxicities in a clinical setting. This review summarizes pathophysiological mechanisms of drug-induced nephrotoxicity, classes of nephrotoxic drugs, management, prevention, and diagnosis in clinics. Finally, it also highlights some of the recent advancements in mathematical M&S approaches that could be used to better understand and predict drug-induced nephrotoxicity.

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“…First, kidney organoids are not a structure amenable to facilitated transport studies. Given that the primary reason an NCE induces nephrotoxicity is accumulation in the proximal tubule (Weber et al, 2017), protocols need to be established for isolation of pure tubule epithelial cells from organoids. Then these cell isolates could be used to populate 3D MPS as previously described.…”

Section: Current Challenges and Future Perspectivesmentioning

confidence: 99%

Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics

Bajaj¹,

Chowdhury²,

Yucha³

et al. 2018

Drug Metab Dispos

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The kidney is a major clearance organ of the body and is responsible for the elimination of many xenobiotics and prescription drugs. With its multitude of uptake and efflux transporters and metabolizing enzymes, the proximal tubule cell (PTC) in the nephron plays a key role in the disposition of xenobiotics and is also a primary site for toxicity. In this minireview, we first provide an overview of the major transporters and metabolizing enzymes in the PTCs responsible for biotransformation and disposition of drugs. Next, we discuss different cell sources that have been used to model PTCs in vitro, their pros and cons, and their characterization. As current technology is inadequate to evaluate reliably drug disposition and toxicity in the kidney, we then discuss recent advancements in kidney microphysiological systems (MPS) and the need to develop robust in vitro platforms that could be routinely used by pharmaceutical companies to screen compounds. Finally, we discuss the new and exciting field of stem cell-derived kidney models as potential cell sources for future kidney MPS. Given the push from both regulatory agencies and pharmaceutical companies to use more predictive "human-like" in vitro systems in the early stages of drug development to reduce attrition, these emerging models have the potential to be a game changer and may revolutionize how renal disposition and kidney toxicity in drug discovery are evaluated in the future.

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Concise review: Current and emerging biomarkers of nephrotoxicity

Cited by 19 publications

References 47 publications

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

A Review on Drug‐Induced Nephrotoxicity: Pathophysiological Mechanisms, Drug Classes, Clinical Management, and Recent Advances in Mathematical Modeling and Simulation Approaches

Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics

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