1898 Clinical Journal of the American Society of Nephrology

Table 1. Nephrotoxic drugs and intoxicants Table 1. (Continued)

Therapeutic medications Environmental intoxicants

Antimicrobial Heavy metals
Aminoglycosides Lead
Antiviral agents Mercury
Amphotericin B Cadmium
Colistin Uranium
Polymixin B Copper
Sulfadiazine Bismuth
Quinolones Solvents
Vancomycin Hydrocarbons
Chemotherapy Other toxins
Platins Silicon
Ifosfamide Germanium
Mitomycin
Gemcitabine NSAIDs, nonsteroidal anti-inflammatory drugs; COX,
Methotrexate cyclo-oxygenase; ACE, angiotensin-converting enzyme;
Pentostatin ARBs, angiotensin-receptor blockers; SGLT-2, sodium glucose
Interleukin-2 (high dose) transporter-2; NaP, sodium phosphate; IVIg, intravenous
Antiangiogenesis agents immunoglobulin; sp., species.
Immunotherapies (immune checkpoint inhibitors, chimeric
antigen receptor T cells)
Analgesics
NSAIDs majority of potentially nephrotoxic medications, many are
Selective COX-2 inhibitors also available as over-the-counter preparations. Radiocon-
Phenacetin trast agents, in particular those delivered intra-arterially at
Analgesic combinations
Immunosuppressives
high dose, are another potential cause of AKI (22,23).
Calcineurin inhibitors In addition to Food and Drug Administration (FDA)–
Sirolimus, everolimus approved medications, unregulated sources of potentially
Other nephrotoxic substances are the alternative/complementary
ACE inhibitors/ARBs/renin inhibitors products, which are widely available at most health food
SGLT-2 inhibitors (canagloflozin, dapagliflozin)
Methoxyflurane stores (17–20). Included are items described as herbal rem-
Sucrose (IVIg excipient), hydroxyethyl starch, mannitol, dextran edies, natural products, and nutritional supplements (16).
Pamidronate, Zolendronate Another concern is that these products often contain a
Topiramate, Zonisamide number of harmful chemicals and/or contaminants that
Orlistat
Statins
are not listed on the label (16–20). Not uncommonly, the
Mesalamine substances listed on the package label are present in varying
Alternative/health products amounts ranging from large, to small, to even nonexistent. In
Herbal remedies addition to direct nephrotoxicity, herbal products may in-
Aristolochic acid teract with conventional drugs producing another potential
Ephedra sp.
Glycyrrhiza sp. avenue of nephrotoxicity. Examples of such unlisted contents
Datura sp. include Ephedra species and aristolochic acid as well herbal
Taxus celebica products adulterated with phenylbutazone and other non-
Uno degatta steroidal anti-inflammatory drugs (NSAIDs), cadmium, and
Cape aloes
Adulterants
dichromate (16–20).
Mefenamic acid
Dichromate
Cadmium
Drug Dose and Duration of Therapy
Phenylbutazone One of the most important parts of drug-induced
Melamine nephrotoxicity is the innate kidney toxicity of the offending
Diagnostic agents agent. A number of drug characteristics and their varied
Radiocontrast mechanisms of action play a role in causing kidney injury
High osmolar
Low osmolar
(Figure 1). High doses and prolonged courses of certain
Iso-osmolar nephrotoxins will enhance risk for kidney injury via exces-
Other agents sive exposure of the kidney, even in patients with minimal
Gadolinium (in high dose) or no underlying risk. Several drugs such as the amino-
Oral NaP solution (colonoscopy prep) glycosides, platinums, amphotericin B, and colistin fall into
this category (24–28).

Drug Characteristics (Solubility, Structure, and Charge)

Drugs and metabolites that are insoluble in the urine
may cause acute crystalline nephropathy by precipitating
in distal tubular lumens (11,29–31). This process is en-
hanced further by reduced urinary flow rates, urine pH
(depending on drug pKa), excessive drug dosing, and rapid