Introduction

Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins are substances displaying nephrotoxicity. Nephrotoxicity should not be confused with the fact that some medications are predominantly excreted by the kidneys and need their dose adjusted for the decreased kidney function (e.g., heparin, lithium).

Nephrotoxicity can be temporary with a temporary elevation of lab values (BUN and/or creatinine).  If these levels are elevated, these may be due to a temporary condition such as dehydration or you may be developing renal (kidney failure). If the cause of the increased BUN and/or creatinine levels is determined early, and your healthcare provider implements the appropriate intervention, permanent kidney problems may be avoided.

Aminoglycoside causes nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multi-ligand receptor megalin. A consensus set of phenotypic criteria for induced nephrotoxicity have recently been published. Novel renal biomarkers, in particular kidney injury molecule-1, identify proximal tubular injury earlier than traditional markers and have shown promise in observational studies. Further studies need to demonstrate a clear association with clinically relevant outcomes to inform translation into clinical practice.

Nephrotoxicity can be diagnosed through a simple blood test. Evaluation of nephrotoxicity through blood tests includes the measurements of blood urea nitrogen (BUN), concentration of serum creatinine, glomerular filtration rate and creatinine clearance. However, these assessments of nephrotoxicity are only possible when a majority of kidney function is damaged. Therefore, discovery and development of biomarkers that can detect kid-ney dysfunction at the early stage are needed. In this review, we summarize the mechanisms of drug-induced nephrotoxicity and highlight their involvement in diseases. We also summarize and present the list of biomarkers for assessment of nephrotoxicity.

Renal toxicity

Renal toxicity associated with sulfonamides is rare as most of the current pharmaceutical preparations are relatively highly soluble at the pH normally occurring in the kidneys. Toxicity occurs due to very high overdosage. Sulfonamides can cause both acute and chronic toxic effects. Animals with renal toxicity will show elevated levels of BUN and creatinine. Knowledge of the complex molecular and pathophysiologic mechanisms leading to nephrotoxicity remains limited, in part, by research that historically focused on single or relatively few risk markers. As such, current kidney injury biomarkers are inadequate in terms of sensitivity and specificity.

In contrast, metabolomics enables screening of a vast array of metabolites simultaneously using NMR and MS to assess their role in nephrotoxicity development and progression. Nephrotoxicity associated with docetaxel administration seems to be limited, although occurrence of hyponatremia and TMA has been reported. Because urinary β2 microglobulin levels are increased after docetaxel administration, docetaxel may have some tubular toxicity.

Nephrotoxicity due to amphotericin occurs in one-third of the patients treated with amphotericin with the risk significantly higher in those treated with high doses. It is important to note that lipid formulation of amphotericin have less nephrotoxicity compared to conventional form.

The Journal of “Clinical Pharmacology and Toxicology Research” is using Editorial Tracking System to maintain quality and transparency to the author in the peer-review process. Review processing will be performed by the editorial board members of the Journal of “Clinical Pharmacology and Toxicology Research” or by Reviewers (outside experts in the field). Two independent reviewer’s approval (Minimum reviewer’s approval) followed by editor approval is obligatory for acceptance of any manuscript excluding an editorial.

Regards,

Mary Wilson,

Editorial office,

Clinical Pharmacology and Toxicology Research

E-mail: pharmatoxicol@eclinicalsci.com