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Renal toxicity caused by diethylene glycol: an overview

  • Nephrology - Review
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Abstract

Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative overview summarizes selected literature with a focus on clinical findings, pathophysiology, diagnosis including morphological features of renal biopsies, and management. The kidney injury in DEG poisoning is secondary to proximal tubular necrosis caused by DGA. Marked vacuolization and edema of epithelial cells obstruct the lumen, reducing urine flow and, consequently, resulting in anuria and uremia. The clinical alterations due to DEG poisoning are dose-dependent. Patients may present with gastrointestinal symptoms and anion gap metabolic acidosis, followed by renal failure, and, later, encephalopathy and neuropathy. Although this three-phase pattern has been described, signs and symptoms may be overlapping. Data about DEG intoxication is scarce. Sometimes the diagnosis is challenging. The management includes supportive care, gastric decontamination, correction of acid–base disorders, and hemodialysis. The understanding of the metabolic processes related to DEG poisoning may contribute to its management, preventing death, serious sequels, or irreversible lesions.

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References

  1. Rentz ED, Lewis L, Mujica OJ, Barr DB, Schier JG, Weerasekera G et al (2008) Outbreak of acute renal failure in Panama in 2006: a case-control study. Bull World Health Organ 86(10):749–756

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alfred S, Coleman P, Harris D, Wigmore T, Stachowski E, Graudins A (2005) Delayed neurologic sequelae resulting from epidemic diethylene glycol poisoning. Clin Toxicol (Phila) 43(3):155–159

    Article  PubMed  Google Scholar 

  3. Alkahtani S, Sammons H, Choonara I (2010) Epidemics of acute renal failure in children (diethylene glycol toxicity). Arch Dis Child 95(12):1062–1064

    Article  PubMed  Google Scholar 

  4. Asmar A, Mohandas R, Wingo CS (2012) A physiologic-based approach to the treatment of a patient with hypokalemia. Am J Kidney Dis 60(3):492–497

    Article  PubMed  PubMed Central  Google Scholar 

  5. Minas Gerais. Secretaria de Estado de Saúde de Minas Gerais. Subsecretaria de Vigilância em Saúde (2020) Nota técnica n°02/COES-SES/MG. Protocolo de intoxicação exógena por dietilenoglicol (DEG). Belo Horizonte: Brasília (DF): Secretaria de Estado de Saúde de Minas Gerais

  6. Song CH, Bae HJ, Ham YR, Na KR, Lee KW, Choi DE (2017) A case of ethylene glycol intoxication with acute renal injury: successful recovery by fomepizole and renal replacement therapy. Electrolyte Blood Press 15(2):47–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wittschieber D, Heuberger K, Schulz R, Köhler H, Varchmin-Schultheiß K (2019) Fatal poisoning with diethylene glycol in an unusual setting. Forensic Sci Med Pathol 15(4):649–652

    Article  CAS  PubMed  Google Scholar 

  8. Hari P, Jain Y, Kabra SK (2006) Fatal encephalopathy and renal failure caused by diethylene glycol poisoning. J Trop Pediatr 52(6):442–444

    Article  PubMed  Google Scholar 

  9. Gopalakrishnan N, Kamarajan M, Balasubramaniyan T, Sakthirajan R, Dhanapriya J, Dineshkumar T (2016) Diethylene glycol poisoning-induced acute kidney injury. Saudi J Kidney Dis Transpl 27:1276–1279

    Article  PubMed  Google Scholar 

  10. Clay KL, Murphy RC, Watkins WD (1975) Experimental methanol toxicity in the primate: analysis of metabolic acidosis. Toxicol Appl Pharmacol 34(1):49–61

    Article  CAS  PubMed  Google Scholar 

  11. Devoti E, Marta E, Belotti E, Bregoli L, Liut F, Maiorca P et al (2015) Diethylene glycol poisoning from transcutaneous absorption. Am J Kidney Dis 65(4):603–606

    Article  PubMed  Google Scholar 

  12. Heilmair R, Lenk W, Lohr D (1993) Toxicokinetics of diethylene glycol (DEG) in the rat. Arch Toxicol 67:655–666

    Article  CAS  PubMed  Google Scholar 

  13. Besenhofer LM, Adegboyega PA, Bartels M, Filary MJ, Perala AW, McLaren MC et al (2010) Inhibition of metabolism of diethylene glycol prevents target organ toxicity in rats. Toxicol Sci 117(1):25–35

    Article  CAS  PubMed  Google Scholar 

  14. Obatomi DK, Bach PH (1996) Inhibition of mitochondrial respiration and oxygen uptake in isolated rat renal tubular fragments by atractyloside. Toxicol Lett 89(2):155–161

    Article  CAS  PubMed  Google Scholar 

  15. Robinson CN, Latimer B, Abreo F, Broussard K, McMartin KE (2017) In-vivo evidence of nephrotoxicity and altered hepatic function in rats following administration of diglycolic acid, a metabolite of diethylene glycol. Clin Toxicol (Phila) 55(3):196–205

    Article  CAS  PubMed  Google Scholar 

  16. Landry GM, Martin S, McMartin KE (2011) Diglycolic acid is the nephrotoxic metabolite in diethylene glycol poisoning inducing necrosis in human proximal tubule cells in vitro. Toxicol Sci 124(1):35–44

    Article  CAS  PubMed  Google Scholar 

  17. Landry GM, Dunning CL, Conrad T, Hitt MJ, McMartin KE (2013) Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death. Toxicol Lett 221(3):176–184

    Article  CAS  PubMed  Google Scholar 

  18. Forkink M, Smeitink JA, Brock R, Willems PH, Koopman WJ (2010) Detection and manipulation of mitochondrial reactive oxygen species in mammalian cells. Biochim Biophys Acta 1797(6–7):1034–1044

    Article  CAS  PubMed  Google Scholar 

  19. Jezek P, Hlavatá L (2005) Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 37(12):2478–2503

    Article  CAS  PubMed  Google Scholar 

  20. Paddenberg R, Ishaq B, Goldenberg A, Faulhammer P, Rose F, Weissmann N et al (2003) Essential role of complex II of the respiratory chain in hypoxia-induced ROS generation in the pulmonary vasculature. Am J Physiol Lung Cell Mol Physiol 284(5):L710–L719

    Article  CAS  PubMed  Google Scholar 

  21. Nowak G, Schnellmann RG (1997) Renal cell regeneration following oxidant exposure: inhibition by TGF-beta1 and stimulation by ascorbic acid. Toxicol Appl Pharmacol 145(1):175–183

    Article  CAS  PubMed  Google Scholar 

  22. Nowak G, Carter CA, Schnellmann RG (2000) Ascorbic acid promotes recovery of cellular functions following toxicant-induced injury. Toxicol Appl Pharmacol 167(1):37–45

    Article  CAS  PubMed  Google Scholar 

  23. Conrad T, Landry GM, Aw TY, Nichols R, McMartin KE (2016) Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro. Clin Toxicol (Phila) 54(6):501–511

    Article  CAS  PubMed  Google Scholar 

  24. Schep LJ, Slaughter RJ, Temple WA, Beasley DM (2009) Diethylene glycol poisoning. Clin Toxicol (Phila) 47(6):525–35. Erratum in: Clin Toxicol (Phila) 47(8):840

  25. Wiley FH (1938) The formation of oxalic acid from ethylene glycol and related solvents. J Ind Hyg Toxicol 20:269–277

    CAS  Google Scholar 

  26. Haag HB, Ambrose AM (1937) Studies of the physiological effect of diethylene glycol: II toxicity and fate. J Pharmacol Exp Ther 59:93–100

    CAS  Google Scholar 

  27. Morelle J, Kanaan N, Hantson P (2010) The Case: Cranial nerve palsy and acute renal failure after a “special drink.” Kidney Int 77(6):559–560

    Article  PubMed  Google Scholar 

  28. Scalzo AJ (1996) Diethylene glycol toxicity revisited: the 1996 Haitian epidemic. J Clin Toxicol 34(5):513–516

    CAS  Google Scholar 

  29. Drut R, Quijano G, Jones MC, Scanferla P (1994) Hallazgos patológicos en la intoxicación por dietilenglicol [Pathologic findings in diethylene glycol poisoning]. Medicina (B Aires) 54(1):1–5

    CAS  PubMed  Google Scholar 

  30. Shubin AV, Demidyuk IV, Komissarov AA, Rafieva LM, Kostrov SV (2016) Cytoplasmic vacuolization in cell death and survival. Oncotarget 7(34):55863–55869

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wordley E (1947) Diethylene Glycol Poisoning: Report on Two Cases. J Clin Pathol 1:44–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Singh J, Dutta AK, Khare S, Dubey NK, Harit AK, Jain NK et al (2001) Diethylene glycol poisoning in Gurgaon, India, 1998. Bull World Health Organ 79(2):88–95

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Heptinstall RH (1968) Pathology of end-stage kidney disease. Am J Med 44(5):656–663

    Article  CAS  PubMed  Google Scholar 

  34. Jain R, Randev S, Kumar P, Guglani V (2021) Acute Kidney Injury and Encephalopathy in a Child: Diethylene Glycol Poisoning. Indian J Pediatr 88(2):194–195

    Article  PubMed  Google Scholar 

  35. Sosa NR, Rodriguez GM, Schier JG, Sejvar JJ (2014) Clinical, laboratory, diagnostic, and histopathologic features of diethylene glycol poisoning–Panama, 2006. Ann Emerg Med 64(1):38–47

    Article  PubMed  Google Scholar 

  36. Marraffa JM, Holland MG, Stork CM, Hoy CD, Hodgman MJ (2008) Diethylene glycol: widely used solvent presents serious poisoning potential. J Emerg Med 35(4):401–406

    Article  PubMed  Google Scholar 

  37. O’Brien KL, Selanikio JD, Hecdivert C, Placide MF, Louis M, Barr DB et al (1998) Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. Acute Renal Failure Investigation Team JAMA 279(15):1175–1180

    CAS  PubMed  Google Scholar 

  38. Imam YZB, Kamran S, Karim H, Elalamy O, Sokrab T, Osman Y et al (2014) Neurological manifestation of recreational fatal and near-fatal diethylene glycol poisonings: case series and review of literature. Medicine (Baltimore) 93(10):e62

    Article  CAS  PubMed  Google Scholar 

  39. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA (2002) American academy of clinical toxicology Ad Hoc committee on the treatment guidelines for methanol poisoning. American academy of clinical toxicology practice guidelines on the treatment of methanol poisoning. J Clin Toxicol. 40(4):415–46

    CAS  Google Scholar 

  40. Brent J, McMartin K, Phillips S, Aaron C, Methylpyrazole for Toxic Alcohols Study Group (2001) Fomepizole for the treatment of methanol poisoning. N Engl J Med. 344(6):424–429

    Article  CAS  PubMed  Google Scholar 

  41. Brooks DE, Wallace KL (2002) Acute propylene glycol ingestion. J Clin Toxicol 40(4):513–516

    Google Scholar 

  42. Rietjens SJ, de Lange DW, Meulenbelt J (2014) Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol? N Engl J Med. 72(2):73–9.z

    CAS  Google Scholar 

  43. Brophy PD, Tenenbein M, Gardner J, Bunchman TE (2000) Smoyer WE (2000) Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis. 35(5):958–62

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was partially supported by Brazilian National Council of Research Development (CNPq—Grant # 302153/2019-5), Coordination of High Education Level Personnel (CAPES), and Foundation of Research of Minas Gerais (FAPEMIG—CDS—APQ-02541-17).

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Authors and Affiliations

  1. Instituto de Nefropatologia, Belo Horizonte, MG, Brasil

    Stanley de Almeida Araújo & David Campos Wanderley

  2. Centro de Microscopia Eletrônica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

    Stanley de Almeida Araújo & David Campos Wanderley

  3. Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais Belo Horizonte, Avenida Alfredo Balena, 190, 2o andar, sala 281, Bairro Santa Efigênia, MG, CEP 30130-100, Brasil

    Bárbara Caroline Dias Faria, Júlia Cunha Vasconcelos, Aniel Feitosa da Cruz, Vitor Santos de Souza & Ana Cristina Simões-e-Silva

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  1. Stanley de Almeida Araújo
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de Almeida Araújo, S., Faria, B.C.D., Vasconcelos, J.C. et al. Renal toxicity caused by diethylene glycol: an overview. Int Urol Nephrol 55, 2867–2875 (2023). https://doi.org/10.1007/s11255-023-03604-2

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