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Nephrotoxicity of Antimicrobials and Antibiotics

      Medication-induced nephrotoxicity remains one of the most common causes of acute kidney injury (AKI) among hospitalized patients. Within the extensive group of medications associated with AKI, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. Clinical manifestations range from mild forms of tubular injury to significant deterioration of kidney function requiring acute renal replacement therapy. Several mechanisms are described, although the most frequent are acute interstitial nephritis, acute tubular necrosis, intratubular crystal deposition, and proximal/distal tubulopathy with electrolyte wasting abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease, and concomitant use of medication with nephrotoxic potential. Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity.

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      References

        • Kim S.Y.
        • Moon A.
        Drug-induced nephrotoxicity and its biomarkers.
        Biomol Ther (Seoul). 2012; 20: 268-272
        • Ho E.S.
        • Lin D.C.
        • Mendel D.B.
        • Cihlar T.
        Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1.
        J Am Soc Nephrol. 2000; 11: 383-393
        • Wijnholds J.
        • Mol C.
        • Deemter L.V.
        • et al.
        Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.
        Proc Natl Acad Sci U S A. 2000; 97: 7476-7481
        • Lechner J.
        • Pfaller W.
        Interferon α2b increases paracellular permeability of renal proximal tubular LLC-PK1 cells via a mitogen activated protein kinase signaling pathway.
        Ren Fail. 2001; 23: 573-588
        • Berns J.S.
        • Cohen R.M.
        • Stumacher R.J.
        • Rudnick M.R.
        Renal aspects of therapy for human immunodeficiency virus and associated opportunistic infections.
        J Am Soc Nephrol. 1991; 1: 1061-1080
        • Perazella M.A.
        Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity.
        Am J Med Sci. 2003; 325: 349-362
        • Coroneos E.
        • Petrusevsk G.
        • Varghes F.
        • Truong D.F.
        Focal segmental glomerulosclerosis with acute renal failure associated with α-interferon therapy.
        Am J Kidney Dis. 1996; 28: 888-892
        • Traynor A.
        • Kuzel T.
        • Samuelson E.
        • Kanwar Y.
        Minimal-change glomerulopathy and glomerular visceral epithelial hyperplasia associated with alpha-interferon therapy for cutaneous T-cell lymphoma.
        Nephron. 1994; 67: 94-100
        • Beaufils H.
        • Deray G.
        • Katlama C.
        • et al.
        Foscarnet and crystals in glomerular capillary lumens.
        Lancet. 1990; 336: 755
        • Sax P.
        • Zolopa A.
        • Brar I.
        • et al.
        Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study.
        J Acquir Immune Defic Syndr. 2014; 67: 52-58
        • Antela A.
        • Aguiar C.
        • Compston J.
        • et al.
        The role of tenofovir alafenamide in future HIV management.
        HIV Med. 2016; 17: 4-16
        • Serota D.P.
        • Franch H.A.
        • Cartwright E.J.
        Acute kidney injury in a patient on tenofovir alafenamide fumarate after initiation of treatment for hepatitis C virus infection.
        Open Forum Infect Dis. 2018; 5: ofy189
        • Labarga P.
        • Barreiro P.
        • Martin-Carbonero L.
        Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.
        AIDS. 2009; 23: 689-696
        • Rodríguez-Nóvoa S.
        • Labarga P.
        • Soriano V.
        Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study.
        Clin Infect Dis. 2009; 48: e108-e116
        • Cooper R.D.
        • Wiebe N.
        • Smith N.
        • Keiser P.
        • Naicker S.
        • Tonelli M.
        Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.
        Clin Infect Dis. 2010; 51: 496-505
        • Daudon M.
        • Estépa L.
        • Viard J.P.
        • Joly D.
        • Jungers P.
        Urinary stones in HIV-1-positive patients treated with indinavir.
        Lancet. 1997; 349: 1294-1295
        • Kopp J.B.
        • Miller K.D.
        • Mican J.A.M.
        • et al.
        Crystalluria and urinary tract abnormalities associated with indinavir.
        Ann Intern Med. 1997; 127: 119-125
        • Fogo A.B.
        • Lusco M.A.
        • Najafian B.
        • Alpers C.E.
        AJKD atlas of renal pathology: indinavir nephrotoxicity.
        Am J Kidney Dis. 2017; 69: e3
        • Eck P.
        • Silver S.M.
        • Clark E.C.
        Acute renal failure and coma after a high dose of oral acyclovir.
        N Engl J Med. 1991; 325: 1178-1179
        • Bean B.
        • Aeppli D.
        Acyclovir-induced renal failure, clinical course and histology.
        Am J Med. 1988; 84: 1067-1071
        • Goldfarb D.S.
        • Coe F.L.
        Foscarnet crystal deposition and renal failure.
        Am J Kidney Dis. 1998; 32: 519-520
        • Bendz H.
        • Aurell M.
        Drug-induced diabetes insipidus incidence, prevention and management.
        Drug Saf. 1999; 21: 449-456
        • Pisoni R.
        • Ruggenenti P.
        • Remuzzi G.
        Drug-induced thrombotic microangiopathy: incidence, prevention and management.
        Drug Saf. 2001; 24: 491-501
        • Rönnblom L.E.
        • Alm G.V.
        • Oberg K.E.
        Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors.
        Ann Intern Med. 1991; 115: 178-183
        • Markowitz G.S.
        • Nasr S.H.
        • Stokes M.B.
        • D'Agati V.D.
        Treatment with IFN-{alpha}, -{beta}, or -{gamma} is associated with collapsing focal segmental glomerulosclerosis.
        Clin J Am Soc Nephrol. 2010; 5: 607-615
        • Moore R.D.
        • Smith C.R.
        • Lipsky J.J.
        • Mellits E.D.
        • Lietman P.S.
        Risk factors for nephrotoxicity in patients treated with aminoglycosides.
        Ann Intern Med. 1984; 100: 352-357
        • Nagai J.
        • Takano M.
        Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity.
        Drug Metab Pharmacokinet. 2004; 19: 159-170
        • Patel R.
        • Savage A.
        Symptomatic hypomagnesemia associated with gentamicin therapy.
        Nephron. 1979; 23: 50-52
        • Muriithi A.K.
        • Nasr S.H.
        • Leung N.
        Utility of urine eosinophils in the diagnosis of acute interstitial nephritis.
        Clin J Am Soc Nephrol. 2013; 8: 1857-1862
        • Burgess L.D.
        • Drew R.H.
        Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam.
        Pharmacotherapy. 2014; 34: 670-676
        • Newman T.J.
        • Dreslinski G.R.
        • Tadros S.S.
        Safety profile of aztreonam in clinical trials.
        Rev Infect Dis. 1985; 7: S648-S655
        • Cotner S.E.
        • Rutter W.F.
        • Burgess D.R.
        Influence of β-lactam infusion strategy on acute kidney injury.
        Antimicrob Agents Chemother. 2017; 61 (e00871-17)
        • Bird S.T.
        • Etminan M.
        • Brophy J.M.
        • Hartzema A.G.
        • Delaney J.A.
        Risk of acute kidney injury associated with the use of fluoroquinolones.
        CMAJ. 2013; 185: E475-E482
        • Thorsteinsson S.B.
        • Bergan T.
        • Oddsdottir S.
        • Rohwedder R.
        • Holm R.
        Crystalluria and ciprofloxacin, influence of urinary pH and hydration.
        Chemotherapy. 1986; 32: 408-417
        • Cheah C.Y.
        • De Keulenaer B.
        • Leahy M.F.
        Fluoroquinolone-induced immune thrombocytopenia: a report and review.
        Intern Med J. 2009; 39: 619-623
        • Bailie G.R.
        • Neal D.
        Vancomycin ototoxicity and nephrotoxicity. A review.
        Med Toxicol Adverse Drug Exp. 1988; 3: 376-386
        • Sinha Ray A.
        • Haikal A.
        • Hammoud K.A.
        • Yu A.S.
        Vancomycin and the risk of AKI: a systematic review and meta-analysis.
        Clin J Am Soc Nephrol. 2016; 11: 2132-2140
        • Cosgrove S.E.
        • Vigliani G.A.
        • Fowler Jr., V.G.
        Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic.
        Clin Infect Dis. 2009; 48: 713-721
        • Kullar R.
        • McClellan I.
        • Geriak M.
        • Sakoulas G.
        Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis.
        Pharmacotherapy. 2014; 34: 582-589
        • Abraham G.
        • Finkelberg D.
        • Spooner L.M.
        Daptomycin-induced acute renal and hepatic toxicity without rhabdomyolysis.
        Ann Pharmacother. 2008; 42: 719-721
        • Li J.
        • Nation R.L.
        • Milne R.W.
        • Turnidge J.D.
        • Coulthard K.
        Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria.
        Int J Antimicrob Agents. 2005; 25: 11-25
        • Nation R.L.
        • Li J.
        Colistin in the 21st century.
        Curr Opin Infect Dis. 2009; 22: 535-543
        • Kim J.
        • Lee K.H.
        • Yoo S.
        • Pai H.
        Clinical characteristics and risk factors of colistin-induced nephrotoxicity.
        Int J Antimicrob Agents. 2009; 34: 434-438
        • Spapen H.
        • Jacobs R.
        • Van Gorp V.
        • Troubleyn J.
        • Honoré P.M.
        Renal and neurological side effects of colistin in critically ill patients.
        Ann Intensive Care. 2011; 1: 14
        • Vardakas K.Z.
        • Falagas M.E.
        Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis.
        Int J Antimicrob Agents. 2017; 49: 233-238
        • Fanos V.
        • Cataldi L.
        Amphotericin B-induced nephrotoxicity: a review.
        J Chemother. 2000; 12: 463-470
        • Branch R.A.
        Prevention of amphotericin B-induced renal impairment. A review on the use of sodium supplementation.
        Arch Intern Med. 1988; 148: 2389-2394
        • Alexander B.D.
        • Wingard J.R.
        Study of renal safety in amphotericin B lipid complex–treated patients.
        Clin Infect Dis. 2005; 40: S414-S421
        • Fisher M.A.
        • Talbot G.H.
        • Maislin G.
        • McKeon B.P.
        • Tynan K.P.
        • Strom B.L.
        Risk factors for amphotericin B-associated nephrotoxicity.
        Am J Med. 1989; 87: 547-552
        • Barrett J.P.
        • Vardulaki K.A.
        • Conlon C.
        • et al.
        A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations.
        Clin Ther. 2003; 25: 1295-1320
        • Bates D.W.
        • Su L.
        • Yu D.T.
        • et al.
        Mortality and cost of acute renal failure associated with amphotericin B therapy.
        Clin Infect Dis. 2001; 32: 686-693
        • Villanueva A.
        • Arathoon E.G.
        • Gotuzzo E.
        • Berman R.S.
        • DiNubile M.J.
        • Sable C.A.
        A randomized double-blind study of caspofungin versus amphotericin for the treatment of Candida esophagitis.
        Clin Infect Dis. 2001; 33: 1529-1535
        • Arathoon E.G.
        • Gotuzzo E.
        • Noriega L.M.
        • Berman R.S.
        • DiNubile M.J.
        • Sable C.A.
        Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases.
        Antimicrob Agents Chemother. 2002; 46: 451-457
        • Walsh T.J.
        • Teppler H.
        • Donowitz G.R.
        • et al.
        Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.
        N Engl J Med. 2004; 351: 1391-1402
        • Wegner B.
        • Baer P.
        • Gauer S.
        • Oremek G.
        • Hauser I.A.
        • Geiger H.
        Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly damages distal renal tubular cells.
        Nephrol Dial Transplant. 2005; 20: 2071-2079