Reports of acute and chronic kidney diseases are increasing in the U.S. and various parts of the world. When looking for a critical metric to understand when not to treat with nephrotoxic medication, we set the standard of having an eGFR less than 60 mL/min per 1.73 m.
Nephrotoxic medications can elicit damage to the kidney via various mechanisms, including alteration in its structure and function. When evaluating the primary etiologies in renal injury, the incidence of drug-induced toxicity has accounted for 20% of all-cause incidents. Besides, when nephrotoxicity from pharmacologic agents is further examined, evidence has shown it to be one of the chief etiologies in intrinsic renal failure aside from the second most common cause, infection. Numerous drugs go under the category of nephrotoxic medications. Tables 1 through 3 are a list of the most common drugs that can damage the kidneys and their drug class.
The more significant percentage of individuals affected by these agents come from the over 70-year-old category. With the aging life expectancy in the United States, we need to choose pharmacologically appropriate agents for our aging population with declining renal functions.
Drugs such as those listed previously elicit damage to renal tissue via numerous mechanisms. A few of these mechanisms include impairment of perfusion, inflammation induction, free radicals formation, and many other mechanisms. A few of the most common mechanisms of action appear below:
A few examples include the effect of ACE inhibitors, ARBs, cyclosporins, NSAIDs, and tacrolimus that affect the intraglomerular hemodynamics via the alteration of the glomerular filtration rate.
Tubular Cell Toxicity
The presence of certain pharmaceutical agents may damage the cells of the proximal tubules via free radical formation, mitochondrial damage, and transport systems damage. These agents include aminoglycosides, amphotericin B, adefovir, cisplatin, and foscarnet.
NSAIDs and rifampin are common causes of acute interstitial tissue inflammation. Chronic forms result from agents, including analgesics, anticancer drugs, lithium, and calcineurin inhibitors.
Antivirals such as acyclovir and antibiotics such as ampicillin have been common etiologies of insoluble crystal formation within renal tissue.
A more detailed list is present in tables 1-3.
The majority of the drugs described are in oral formulations, with a few minor ones available in other forms of administration.
As adverse reactions are the main subject, the full list of renal damage locations appears in tables 1 and 2. Primary sites include the glomerulus and, proximal and distal convoluted renal tubules.
Contraindications to drug administration include the presence of chronic renal disease or end-stage renal disease. As previously mentioned, the presence of a GFR below 60 ml/min per 1.73 m^2 for the definition of moderate chronic renal disease and a creatinine clearance below 30 mL/min as seen in severe chronic kidney disease are critical metrics for treatment judgment.
General guidelines recommend determining baseline renal function before and after initiation of nephrotoxic pharmaceutical agents. The most common formula used in the calculation of glomerular filtration rate is the Schwartz formula. Calculation of GFR (mL/min/1.73 m^2= length (cm) X potassium /serum creatinine (mg/dL). To use clinician judgment in determining whether to withdraw a nephrotoxic agent, we aim to keep the GFR above the chronic kidney disease threshold of 60.
Also, many biomarkers have become available to assess renal toxicity further. A few of these are as follows:
Urine Proteins and Enzymatic activity
Kidney injury Molecule 1
Neutrophil Gelatinase-associated Lipocalin
Type 4 Collagen
Preventative measures aimed at decreasing the incidence of significant nephrotoxic effects include oral administration, low effective doses, and short therapy. Furthermore, the dose can be reduced or discontinued in the setting of toxicity.
In the event that there is a significant nephrotoxic event that is changing the GFR, isotonic repletion can be provided to help dilute serum drug concentrations during therapy. Infants and young children are also a chief demographic in drug-induced nephrotoxicity. Toxicity can present with many different types of renal pathology:
Having an understanding of the different regions of renal damage may allow for a more targeted approach to renal injury, including the development of pharmaceutical agents with greater benefit and decreased toxicity.
Understanding of nephrotoxic pharmaceutical agents is a key component of the interprofessional healthcare team and a patient-centered approach. Starting from the physicians who prescribe the drugs, to the pharmacists who dispense the drug, and the nurses who administer the drugs, there is a chain of transport where many healthcare providers are a part of patient care. Knowing the toxic effects, these agents may present of great importance to the quality of care a patient receives. The nurse should be aware of which drugs are nephrotoxic, especially with patients that already have renal impairment. They can counsel the patients regarding these agents, and report any issues back to the prescriber. The pharmacist can reinforce this counsel, while also performing total medication reconciliation, checking doses (especially those that require renal adjustment), and contacting the clinician if there are any issues. These types of interprofessional collaborations will prevent renal toxicity from occurring when it need not. [Level 5]
Furthermore, through the understanding of preventative measures and thresholds for toxicity, healthcare providers may enhance patient safety. Lastly, with the development of numerous biomarkers targets to types of renal damage, response to treatment can be monitored when a knowledge of the potential renal effects of medication is known. [Level I] 
|||Kaufman J,Dhakal M,Patel B,Hamburger R, Community-acquired acute renal failure. American journal of kidney diseases : the official journal of the National Kidney Foundation. 1991 Feb; [PubMed PMID: 1992662]|
|||Ghane Shahrbaf F,Assadi F, Drug-induced renal disorders. Journal of renal injury prevention. 2015; [PubMed PMID: 26468475]|
|||Schetz M,Dasta J,Goldstein S,Golper T, Drug-induced acute kidney injury. Current opinion in critical care. 2005 Dec; [PubMed PMID: 16292059]|
|||Perazella MA, Drug-induced nephropathy: an update. Expert opinion on drug safety. 2005 Jul [PubMed PMID: 16011448]|
|||Markowitz GS,Fine PL,Stack JI,Kunis CL,Radhakrishnan J,Palecki W,Park J,Nasr SH,Hoh S,Siegel DS,D'Agati VD, Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney international. 2003 Jul; [PubMed PMID: 12787420]|
|||Perneger TV,Whelton PK,Klag MJ, Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. The New England journal of medicine. 1994 Dec 22 [PubMed PMID: 7969358]|
|||Markowitz GS,Perazella MA, Drug-induced renal failure: a focus on tubulointerstitial disease. Clinica chimica acta; international journal of clinical chemistry. 2005 Jan [PubMed PMID: 15563870]|
|||Ingrasciotta Y,Sultana J,Giorgianni F,Caputi AP,Arcoraci V,Tari DU,Linguiti C,Perrotta M,Nucita A,Pellegrini F,Fontana A,Cavagna L,Santoro D,Trifirò G, The burden of nephrotoxic drug prescriptions in patients with chronic kidney disease: a retrospective population-based study in Southern Italy. PloS one. 2014; [PubMed PMID: 24558471]|
|||Ferguson MA,Vaidya VS,Bonventre JV, Biomarkers of nephrotoxic acute kidney injury. Toxicology. 2008 Mar 20; [PubMed PMID: 18294749]|
|||Vaidya VS,Ferguson MA,Bonventre JV, Biomarkers of acute kidney injury. Annual review of pharmacology and toxicology. 2008; [PubMed PMID: 17937594]|
|||Nerlich AG,Schleicher ED,Wiest I,Specks U,Timpl R, Immunohistochemical localization of collagen VI in diabetic glomeruli. Kidney international. 1994 Jun; [PubMed PMID: 7933812]|
|||Alchi B,Nishi S,Kondo D,Kaneko Y,Matsuki A,Imai N,Ueno M,Iguchi S,Sakatsume M,Narita I,Yamamoto T,Gejyo F, Osteopontin expression in acute renal allograft rejection. Kidney international. 2005 Mar; [PubMed PMID: 15698428]|
|||Guo X,Nzerue C, How to prevent, recognize, and treat drug-induced nephrotoxicity. Cleveland Clinic journal of medicine. 2002 Apr; [PubMed PMID: 11996200]|
|||Kim SY,Moon A, Drug-induced nephrotoxicity and its biomarkers. Biomolecules [PubMed PMID: 24130922]|
|||Choudhury D,Ahmed Z, Drug-associated renal dysfunction and injury. Nature clinical practice. Nephrology. 2006 Feb; [PubMed PMID: 16932399]|
|||Bonventre JV,Vaidya VS,Schmouder R,Feig P,Dieterle F, Next-generation biomarkers for detecting kidney toxicity. Nature biotechnology. 2010 May [PubMed PMID: 20458311]|