Nephrotoxicity: A growing problem or an exaggerated fear with unpredictable dimensions?

Published:November 25, 2021DOI:
      Nephrotoxicity is not only a simple matter of a sudden rise in creatinine followed by a return to normal. In many cases, this scenario may be seen without any permanent damage, but in others an acute kidney injury (AKI) episode may progress to some long-term sequelae and affect both the quality and the duration of life. Some discussions of drug-induced nephrotoxicity may be a matter of life and dialysis (e.g. curing a cancer patient with a nephrotoxic chemotherapy regimen but leading to end-stage kidney disease). In certain conditions, the discussion may turn around delaying a life-changing diagnostic/therapeutic intervention (e.g. delaying or not performing a percutaneous coronary intervention due to risk of radiocontrast exposure) or not prescribing a pain killer (like a lower-dose non-steroidal anti-inflammatory drug use for a short term) due to an exaggerated fear of nephrotoxicity. As times change, both for the demographics of people or patients (more elderly, sometimes fragile populations) as well as the therapeutic armamentarium (novel drugs, polypharmacy), there is a careful need to review the scope of nephrotoxicity from time to time. In this issue of the European Journal of Internal Medicine, Robert Unwin discusses the rising problem of toxic nephropathy by highlighting some of the practical aspects [
      • Unwin R.J.
      Toxic nephropathy: adverse renal effects caused by drugs.
      ]. Kidneys are the most sensitive organs to many toxic exposures as there is much more delivery and accumulation of drugs or other nephrotoxic materials due to the high blood flow to the kidneys. The vulnerability of the tubular system, especially the proximal tubules’ high ATP requirement for solute reabsorption, excretion and metabolism, augments the problem of nephrotoxicity in certain conditions [
      • Unwin R.J.
      Toxic nephropathy: adverse renal effects caused by drugs.
      ]. However, the real dimensions or epidemiology of nephrotoxicity still remain to be defined. In most cases, there is no clue to find an offending nephrotoxic exposure in a patient with AKI or acute tubulointerstitial nephritis (TIN), or in some cases it is impossible to detect a causal relationship with the potential nephrotoxin. The definitions of nephrotoxicity that have changed over the years also make it difficult to draw the scope of the problem. Changing definitions or changing therapeutics (like old versus new chemotherapies or contrast agents) lead to a great challenge for providing an exact incidence or prevalence data for nephrotoxicity associated with acute or chronic kidney injury/disease. Given these challenges, Awdishu and Mehta proposed a framework for drug-induced kidney disease (DIKD) as 6 R's: Risk evaluation, timely Recognition, effective Response, Renal support, proper Rehabilitation and more Research [
      • Awdishu L.
      • Mehta R.L.
      The 6R's of drug induced nephrotoxicity.
      ]. This framework may also be used for non-drug nephrotoxicities arising from over-the-counter (OTC) medications, herbal products or environmental toxins.
      To read this article in full you will need to make a payment


        • Unwin R.J.
        Toxic nephropathy: adverse renal effects caused by drugs.
        Eur J Intern Med. 2021;
        • Awdishu L.
        • Mehta R.L.
        The 6R's of drug induced nephrotoxicity.
        BMC Nephrol. 2017; 18: 124
        • Martin M.
        • Wilson F.P.
        Utility of electronic medical record alerts to prevent drug nephrotoxicity.
        Clin J Am Soc Nephrol. 2019; 14: 115-123
        • Piller V.
        • Jarlborg P.
        • Morère P.H.
        Contrast induced nephropathy : myth or reality ?.
        Rev Med Suisse. 2019; 15: 206-210
        • Murray J.
        • Balmuri A.
        • Saurav A.
        • Smer A.
        • Alla V.M.
        Impact of chronic kidney disease on utilization of coronary angiography and percutaneous coronary intervention, and their outcomes in patients with non-ST elevation myocardial infarction.
        Am J Cardiol. 2018; 122: 1830-1836
        • Güven D.C.
        • Ozbek D.A.
        • Sahin T.K.
        • Aksun M.S.
        • Kavgaci G.
        • Cebrayilov C.
        • et al.
        Mo368. The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors: a real-life study.
        Nephrol Dial Transplant. 2021; 36: i253
        • Barnett L.M.A.
        • Cummings B.S.
        Nephrotoxicity and renal pathophysiology: a contemporary perspective.
        Toxicol Sci. 2018; 164: 379-390
        • Belliere J.
        • Mazieres J.
        • Meyer N.
        • Chebane L.
        • Despas F.
        Renal complications related to checkpoint inhibitors: diagnostic and therapeutic strategies.
        Diagnostics. 2021; 11 (Basel)
        • De Broe M.E.
        • Vervaet B.A.
        Is an environmental nephrotoxin the primary cause of CKDu (Mesoamerican nephropathy)? PRO.
        Kidney 360. 2020; 1: 591-595
        • Gobe G.C.
        • Coombes J.S.
        • Fassett R.G.
        • Endre Z.H.
        Biomarkers of drug-induced acute kidney injury in the adult.
        Expert Opin Drug Metab Toxicol. 2015; 11: 1683-1694
        • Awdishu L.
        • Atilano-Roque A.
        • Tuey S.
        • Joy M.S.
        Identification of novel biomarkers for predicting kidney injury due to drugs using "omic" strategies.
        Pharmgenom Pers Med. 2020; 13: 687-705
        • Tuttle K.R.
        • Alicic R.Z.
        • Duru O.K.
        • Jones C.R.
        • Daratha K.B.
        • Nicholas S.B.
        • et al.
        Clinical characteristics of and risk factors for chronic kidney disease among adults and children: an analysis of the CURE-CKD registry.
        JAMA Netw Open. 2019; 2e1918169
        • Perazella M.A.
        Pharmacology behind common drug nephrotoxicities.
        Clin J Am Soc Nephrol. 2018; 13: 1897-1908
        • Kulkarni P.
        Prediction of drug-induced kidney injury in drug discovery.
        Drug Metab Rev. 2021; 53: 234-244