Abstract
Background
Acute kidney injury represents a major adverse effect of vancomycin administration. The aim of the present study is to accumulate all biopsy-proven cases of vancomycin nephrotoxicity and assess the association of histopathological features with renal prognosis.
Methods
Medline, Scopus, CENTRAL, Web of Science, and Clinicaltrials.gov were systematically searched from inception to 29 September 2020. All case reports/series providing individual data of patients with biopsy-proven vancomycin nephrotoxicity were held eligible. A time-to-event analysis was performed evaluating the effects of histological diagnosis on renal recovery.
Results
Overall, 18 studies were included, comprising 21 patients. Acute tubulointerstitial nephritis was the predominant pattern in 9 patients and was associated with a significantly higher risk of permanent renal dysfunction (HR: 5.08, 95% CI: [1.05–24.50)] compared to acute tubular necrosis. Tubulitis and eosinophilic infiltration were the most common histopathological findings, while interstitial fibrosis was linked to significantly worse renal prognosis (HR: 5.55, 95% CI: 1.13–27.27). Immunofluorescence and electron microscopy features were non-specific. Obstruction by tubular casts composed of vancomycin aggregates and uromodulin has been identified as a new mechanism of nephrotoxicity.
Conclusions
Acute tubular necrosis and tubulointerstitial nephritis represent the main histological patterns of vancomycin-induced acute kidney injury. The presence of fibrosis in the context of interstitial inflammation may be linked to lower recovery rates and worse long-term renal outcomes. A novel cast nephropathy obstructive mechanism has been suggested, necessitating further confirmation. Large-scale studies should define the exact indications of kidney biopsy in cases with suspected vancomycin nephrotoxicity.
Similar content being viewed by others
References
Holmes NE, Tong SYC, Davis JS, Hal SJV (2015) Treatment of methicillin-resistant Staphylococcus aureus: vancomycin and beyond. Semin Respir Crit Care Med 36:17–30. https://doi.org/10.1055/s-0034-1397040
Filippone EJ, Kraft WK, Farber JL (2017) The nephrotoxicity of vancomycin. Clin Pharmacol Ther 102:459–469. https://doi.org/10.1002/cpt.726
Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A (2012) Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol 68:1243–1255. https://doi.org/10.1007/s00228-012-1259-9
Rybak MJ, Albrecht LM, Boike SC, Chandrasekar PH (1990) Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother 25:679–687. https://doi.org/10.1093/jac/25.4.679
Bellos I, Karageorgiou V, Pergialiotis V, Perrea DN (2020) Acute kidney injury following the concurrent administration of antipseudomonal β-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect 26:696–705. https://doi.org/10.1016/j.cmi.2020.03.019
Bellos I, Daskalakis G, Pergialiotis V (2020) Relationship of vancomycin trough levels with acute kidney injury risk: an exposure–toxicity meta-analysis. J Antimicrob Chemother 75:2725–2734. https://doi.org/10.1093/jac/dkaa184
Drennan PG, Begg EJ, Gardiner SJ, Kirkpatrick CMJ, Chambers ST (2019) The dosing and monitoring of vancomycin: what is the best way forward? Int J Antimicrob Agents 53:401–407. https://doi.org/10.1016/j.ijantimicag.2018.12.014
Mergenhagen KA, Borton AR (2014) Vancomycin nephrotoxicity: a review. J Pharm Pract 27:545–553. https://doi.org/10.1177/0897190014546114
Pais GM, Liu J, Zepcan S, Avedissian SN, Rhodes NJ, Downes KJ et al (2020) Vancomycin-Induced kidney injury: animal models of toxicodynamics, mechanisms of injury, human translation, and potential strategies for prevention. Pharmacother J Hum Pharmacol Drug Ther 40:438–454. https://doi.org/10.1002/phar.2388
Dalaklioglu S, Tekcan M, Gungor NE, Celik-Ozenci C, Aksoy NH, Baykal A et al (2010) Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury. Toxicol Lett 192:91–96. https://doi.org/10.1016/j.toxlet.2009.10.002
Perazella MA (2019) Drug-induced acute kidney injury: diverse mechanisms of tubular injury. Curr Opin Crit Care 25:550–557. https://doi.org/10.1097/MCC.0000000000000653
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700
Greenhalgh T, Peacock R (2005) Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources. BMJ 331:1064–1065. https://doi.org/10.1136/bmj.38636.593461.68
Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C et al (2020) Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Heal Pharm. https://doi.org/10.1093/ajhp/zxaa036
Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron 120:c179–c184. https://doi.org/10.1159/000339789
Pannu N, James M, Hemmelgarn B, Klarenbach S (2013) Association between AKI, recovery of renal function, and long-term outcomes after hospital discharge. Clin J Am Soc Nephrol 8:194–202. https://doi.org/10.2215/CJN.06480612
Murad MH, Sultan S, Haffar S, Bazerbachi F (2018) Methodological quality and synthesis of case series and case reports. BMJ Evidence-Based Med 23:60–63. https://doi.org/10.1136/BMJEBM-2017-110853
Therneau T. A package for survival analysis in R 2020
Mishra P, Pandey CM, Singh U, Gupta A, Sahu C, Keshri A (2019) Descriptive statistics and normality tests for statistical data. Ann Card Anaesth 22:67–72. https://doi.org/10.4103/aca.ACA_157_18
Fay MP, Proschan MA (2010) Wilcoxon-Mann-Whitney or T-test? on assumptions for hypothesis tests and multiple interpretations of decision rules. Stat Surv 4:1–39. https://doi.org/10.1214/09-SS051
George B, Seals S, Aban I (2014) Survival analysis and regression models. J Nucl Cardiol 21:686–694. https://doi.org/10.1007/s12350-014-9908-2
Marik PE, Ferris N (1997) Delayed hypersensitivity reaction to vancomycin. Pharmacotherapy 17:1341–1344. https://doi.org/10.1002/j.1875-9114.1997.tb03104.x
Hauben M, Adler C (1995) Acute hepatitis, interstitial nephritis, and eosinophilia. Ann Intern Med 122:555–556. https://doi.org/10.7326/0003-4819-122-7-199504010-00020
Ratner SJ (1988) Vancomycin-induced interstitial nephritis. Am J Med 84:561–562. https://doi.org/10.1016/0002-9343(88)90287-2
Eisenberg ES, Robbins N, Lenci M (1981) Vancomycin and interstitial nephritis. Ann Intern Med 95:658. https://doi.org/10.7326/0003-4819-95-5-658_1
Bergman MM, Glew RH, Ebert TH (1988) Acute interstitial nephritis associated with vancomycin therapy. Arch Intern Med 148:2139–2140. https://doi.org/10.1001/archinte.1988.00380100037008
Plakogiannis R, Nogid A (2007) Acute interstitial nephritis associated with coadministration of vancomycin and ceftriaxone: case series and review of the literature. Pharmacotherapy 27:1456–1461. https://doi.org/10.1592/phco.27.10.1456
Babigumira M, Huang B, Werner S, Qunibi W (2017) Delayed manifestation of shunt nephritis: a case report and review of the literature. Case Rep Nephrol 2017:1–9. https://doi.org/10.1155/2017/1867349
Hsu SIH (2001) Biopsy-proved acute tubulointerstitial nephritis and toxic epidermal necrolysis associated with vancomycin. Pharmacotherapy 21:1233–1239. https://doi.org/10.1592/phco.21.15.1233.33901
Pingili CS, Okon EE (2017) Vancomycin-induced leukocytoclastic vasculitis and acute renal failure due to tubulointerstitial nephritis. Am J Case Rep 18:1024-1027. https://doi.org/10.12659/AJCR.905214
Michail S, Vaiopoulos G, Nakopoulou L, Revenas C, Aroni K, Karam P et al (1998) Henoch-Schoenlein purpura and acute interstitial nephritis after intravenous vancomycin administration in a patient with a staphylococcal infection. Scand J Rheumatol 27:233–235. https://doi.org/10.1080/030097498440886
Codding CE, Ramseyer L, Allon M, Pitha J, Rodriguez M (1989) Tubulointerstitial nephritis due to vancomycin. Am J Kidney Dis 14:512–515. https://doi.org/10.1016/S0272-6386(89)80152-0
Gelfand MS, Cleveland KO, Mazumder SA (2014) Vancomycin-induced interstitial nephritis superimposed on coexisting renal disease: the importance of renal biopsy. Am J Med Sci 347:338–340. https://doi.org/10.1097/MAJ.0000000000000240
Hong S, Valderrama E, Mattana J, Shah HH, Wagner JD, Esposito M et al (2007) Vancomycin-induced acute granulomatous interstitial nephritis: therapeutic options. Am J Med Sci 334:296–300. https://doi.org/10.1097/MAJ.0b013e3180a6ec1e
Fahal IH (2014) Uremic sarcopenia: aetiolgy & implications. Ndt 16:518–524. https://doi.org/10.1093/NDT
Wu CY, Wang JS, Chiou YH, Chen CY, Su YT (2007) Biopsy proven acute tubular necrosis associated with vancomycin in a child: case report and literature review. Ren Fail 29:1059–1061. https://doi.org/10.1080/08860220701643773
Wicklow BA, Ogborn MR, Gibson IW, Blydt-Hansen TD (2006) Biopsy-proven acute tubular necrosis in a child attributed to vancomycin intoxication. Pediatr Nephrol 21:1194–1196. https://doi.org/10.1007/s00467-006-0152-0
Wai AO, Lo AMS, Abdo A, Marra F (1998) Vancomycin-induced acute interstitial nephritis. Ann Pharmacother 32:1160–1164. https://doi.org/10.1345/aph.17448
Farheen S-K, Scheetz MH, Ghossein C (2011) Biopsy-proven acute tubular necrosis due to vancomycin toxicity. Int J Nephrol 2011:436856. https://doi.org/10.4061/2011/436856
Htike NL, Santoro J, Gilbert B, Elfenbein IB, Teehan G (2012) Biopsy-proven vancomycin-associated interstitial nephritis and acute tubular necrosis. Clin Exp Nephrol 16:320–324. https://doi.org/10.1007/s10157-011-0559-1
Belen C, Budhiraja P, Bracamonte E, Popovtzer M (2012) Biopsy-proven acute tubular necrosis associated with vancomycin in an adult patient. Ren Fail 34:502–505. https://doi.org/10.3109/0886022X.2012.655683
Kim KM, Sung K, Yang HK, Kim SH, Kim HY, Ban GH et al (2016) Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident post-infectious glomerulonephritis. Korean J Pediatr 59:145–148. https://doi.org/10.3345/kjp.2016.59.3.145
Luque Y, Louis K, Jouanneau C, Placier S, Esteve E, Bazin D et al (2017) Vancomycin-associated cast nephropathy. J Am Soc Nephrol 28:1723–1728. https://doi.org/10.1681/ASN.2016080867
Sawada A, Kawanishi K, Morikawa S, Nakano T, Kodama M, Mitobe M et al (2018) Biopsy-proven vancomycin-induced acute kidney injury: a case report and literature review. BMC Nephrol 19(1):72. https://doi.org/10.1186/s12882-018-0845-1
Tantranont N, Obi C, Luque Y, Truong LD (2019) Vancomycin nephrotoxicity: vancomycin tubular casts with characteristic electron microscopic findings. Clin Nephrol Case Stud 7:66–72. https://doi.org/10.5414/cncs109817
Katikaneni M, Lwin L, Villanueva H, Yoo J (2016) Acute kidney injury associated with vancomycin when laxity leads to injury and findings on kidney biopsy. Am J Ther 23:e1064–e1067. https://doi.org/10.1097/MJT.0000000000000287
Perazella MA, Markowitz GS (2010) Drug-induced acute interstitial nephritis. Nat Rev Nephrol 6:461–470. https://doi.org/10.1038/nrneph.2010.71
Yun D, Jang MJ, An JN, Lee JP, Kim DK, Chin HJ et al (2019) Effect of steroids and relevant cytokine analysis in acute tubulointerstitial nephritis. BMC Nephrol 20:88. https://doi.org/10.1186/s12882-019-1277-2
Esteve E, Luque Y, Waeytens J, Bazin D, Mesnard L, Jouanneau C et al (2020) Nanometric Chemical speciation of abnormal deposits in kidney biopsy: infrared-nanospectroscopy reveals heterogeneities within vancomycin casts. Anal Chem 92:7388–7392. https://doi.org/10.1021/acs.analchem.0c00290
Waikar SS, McMahon GM (2018) Expanding the role for kidney biopsies in acute kidney injury. Semin Nephrol 38:12–20. https://doi.org/10.1016/j.semnephrol.2017.09.001
Legrand M, Mebazaa A (2013) Kidney biopsies in the ICU: is it worth the risk? Minerva Anestesiol 79:5–6
Bellos I, Daskalakis G, Pergialiotis V (2020) Relationship of vancomycin trough levels with acute kidney injury risk: an exposure-toxicity meta-analysis. J Antimicrob Chemother 75:2725–2734. https://doi.org/10.1093/JAC/DKAA184
Badri S, Soltani R, Sayadi M, Khorvash F, Meidani M, Taheri S (2020) Effect of N-acetylcysteine against vancomycin-induced nephrotoxicity: a randomized controlled clinical trial. Arch Iran Med 23:397–402. https://doi.org/10.34172/aim.2020.33
Takigawa M, Yatsu T, Takino Y, Matsumoto S, Kitano T, Lee J et al (2019) High-dose vitamin C preadministration reduces vancomycin-associated nephrotoxicity in mice. J Nutr Sci Vitaminol (Tokyo) 65:399–404. https://doi.org/10.3177/jnsv.65.399
Soltani R, Khorvash F, Meidani M, Badri S, Alaei S, Taheri S (2020) Vitamin e in the prevention of vancomycin-induced nephrotoxicity. Res Pharm Sci 15:137–143. https://doi.org/10.4103/1735-5362.283813
Hori Y, Aoki N, Kuwahara S, Hosojima M, Kaseda R, Goto S et al (2017) Megalin blockade with cilastatin suppresses drug-induced nephrotoxicity. J Am Soc Nephrol 28:1783–1791. https://doi.org/10.1681/ASN.2016060606
Pais GM, Avedissian SN, Nicholas O’Donnell J, Rhodes NJ, Lodise TP, Prozialeck WC et al (2019) Comparative performance of urinary biomarkers for vancomycin-induced kidney injury according to timeline of injury. Antimicrob Agents Chemother 63:e00079. https://doi.org/10.1128/AAC.00079-19
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Informed consent
The present systematic review is based on aggregated data that were retrieved from studies already retrieved. We did not collect individual patient data and did not have direct contact with patients included.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bellos, I., Pergialiotis, V. & Perrea, D.N. Kidney biopsy findings in vancomycin-induced acute kidney injury: a pooled analysis. Int Urol Nephrol 54, 137–148 (2022). https://doi.org/10.1007/s11255-021-02831-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-021-02831-9