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Lithium poisoning and renal replacement therapy: pathophysiology and current clinical recommendations

  • Nephrology - Review
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Abstract

Lithium intoxication is still an undefined and underestimated disease, especially those cases requiring extracorporeal treatment. Lithium is a monovalent cation with small molecular mass of 7 Da that has been regularly and successfully used since 1950 in the treatment of mania and bipolar disorders. However, its careless assumption can lead to a wide spectrum of cardiovascular, central nervous system and kidney diseases in case of acute, acute on chronic and chronic intoxications. In fact, lithium serum range is strict between 0.6 and 1.3 mmol/L, with a mild lithium toxicity observed at the steady-state of 1.5–2.5 mEq/L, moderate toxicity when lithium reaches 2.5–3.5 mEq/L, and severe intoxication with observed serum levels > 3.5 mEq/L. Its favorable biochemical profile allows the complete filtration and partial reabsorption in the kidney due to the similarity to sodium and also the complete removal by renal replacement therapy, that should be considered in specific poisoning conditions. In this narrative and updated review we discussed a clinical case of lithium intoxication, the different pattern of diseases attributable to excessive lithium load and the current indications for extracorporeal treatment.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Baird-Gunning J, Lea-Henry T, Hoegberg LCG et al (2017) Lithium poisoning. J Intensive Care Med 32(4):249263

    Article  Google Scholar 

  2. Rhee T, Olfson M, Nierenberg A, Wilkinson S (2020) 20-Year trends in the pharmacologic treatment of bipolar disorder by psychiatrists in outpatient care settings. Am J Psychiatry 177(8):706–715. https://doi.org/10.1176/appi.ajp.2020.19091000

    Article  PubMed  PubMed Central  Google Scholar 

  3. Meltzer H (2012) Antipsychotic agents and lithium. In: Katsung BG, Masters SB, Trevor AJ (eds) Basic and clinical pharmacology, 12th edn. McGraw-Hill Medical, New York, pp 501–520

    Google Scholar 

  4. Timmer RT, Sands JM (1999) Lithium intoxication. J Am Soc Nephrol 10:666–674

    Article  CAS  PubMed  Google Scholar 

  5. Khasraw M, Ashley D, Wheeler G, Berk M (2012) Using lithium as a neuroprotective agent in patients with cancer. BMC Med 10:131–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gosselin S, Juurlink DN, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, Hoffman RS (2014) Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 52:856–867

    Article  CAS  PubMed  Google Scholar 

  7. Finley PR, Warner MD, Peabody CA (1995) Clinical relevance of drug interactions with lithium. Clin Pharmacokinet 29:172–191

    Article  CAS  PubMed  Google Scholar 

  8. Okusa MD, Crystal LJ (1994) Clinical manifestations and management of acute lithium intoxication. Am J Med 97:383–389

    Article  CAS  PubMed  Google Scholar 

  9. Porto FH, Leite MA, Fontenelle LF, Marrocos RP, Szczerback NF, de Freitas MR (2009) The syndrome of irreversible lithium-effectuated neurotoxicity (SILENT): one-year follow-up of a single case. J Neurol Sci 277:172–173

    Article  PubMed  Google Scholar 

  10. Adityanjee, Munshi KR, Thampy A (2005) The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol 28:38–49

    Article  CAS  PubMed  Google Scholar 

  11. ZalloAtxutegi E, Pacheco MT, Izaguirre NB, Ansorena MAP (2008) Syndrome of irreversible lithium-effectuated neurotoxicity. A propos of a case. Psiquiatr Biol 15:56–58

    Google Scholar 

  12. Robben JH, Knoers NV, Deen PM (2006) Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Ren Physiol 291(2):F257–F270

    Article  CAS  Google Scholar 

  13. Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E (2011) alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. J Am Soc Nephrol 22(2):253–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Grunfeld J, Rossier B (2009) Lithium nephrotoxicity revisited. Nat Rev Nephrol 5(5):270–276. https://doi.org/10.1038/nrneph.2009.43

    Article  CAS  PubMed  Google Scholar 

  15. Tandon P, Wong N, Zaltzman J (2015) Lithium-induced minimal change disease and acute kidney injury. N Am J Med Sci 7(7):328. https://doi.org/10.4103/1947-2714.161252

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bosquet S, Descombes E, Gauthier T, Fellay G, Regamey C (1997) Nephrotic syndrome during lithium therapy. Nephrol Dial Transplant 12(12):2728–2731. https://doi.org/10.1093/ndt/12.12.2728

    Article  CAS  PubMed  Google Scholar 

  17. Lavergne V, Nolin TD, Hoffman RS, Roberts D, Gosselin S, Goldfarb DS, Kielstein JT, Mactier R, Maclaren R, Mowry JB, Bunchman TE, Juurlink D, Megarbane B, Anseeuw K, Winchester JF, Dargan PI, Liu KD, Hoegberg LC, Li Y, Calello DP, Burdmann EA, Yates C, Laliberté M, Decker BS, Mello-DaSilva CA, Lavonas E, Ghannoum M (2012) The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology. Clin Toxicol (Phila) 50:403–413

    Article  PubMed  Google Scholar 

  18. Anonymous (2004) Position paper: whole bowel irrigation. J Toxicol Clin Toxicol 42(6):843–854

  19. BretaudeauDeguigne M, Hamel JF, Boels D, Harry P (2013) Lithium poisoning: the value of early digestive tract decontamination. Clin Toxicol (Phila) 51:243–248

    Article  CAS  Google Scholar 

  20. Scharman EJ (1997) Methods used to decrease lithium absorption or enhance elimination. J Toxicol Clin Toxicol 35:601–608

    Article  CAS  PubMed  Google Scholar 

  21. Zimmerman JL (2003) Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med 31:2794–2801

    Article  PubMed  Google Scholar 

  22. Waring WS (2006) Management of lithium toxicity. Toxicol Rev 25:221–230

    Article  CAS  PubMed  Google Scholar 

  23. Ott M, Stegmayr B, Renberg ES, Werneke U (2016) Lithium intoxication: incidence, clinical course and renal function- a population based retrospective cohort study. J Psychopharmacol 30(10):1008–1019. https://doi.org/10.1177/0269881116652577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Von Hartitzsch B, Hoenich NA, Leigh RJ, Wilkinson R, Frost TH, Weddel A, Posen GA (1972) Permanent neurological sequelae despite haemodialysis for lithium intoxication. BMJ 4:757–759

    Article  Google Scholar 

  25. Bailey AR, Sathianathan VJ, Chiew AL, Paterson AD, Chan BS, Arora S (2011) Comparison of intermittent haemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement haemofiltration for lithium toxicity: a case report. Crit Care Resusc 13:120–122

    PubMed  Google Scholar 

  26. Goodman JW, Goldfarb DS (2006) The role of continuous renal replacement therapy in the treatment of poisoning. Semin Dial 19:402–407

    Article  PubMed  Google Scholar 

  27. Hazouard E, Ferrandière M, Rateau H, Doucet O, Perrotin D, Legras A (1999) Continuous veno-venous haemofiltration versus continuous veno-venous haemodialysis in severe lithium self-poisoning: a toxicokinetics study in an intensive care unit. Nephrol Dial Transplant 14:1605–1606

    Article  CAS  PubMed  Google Scholar 

  28. Wilson JH, Donker AJ, van der Hem GK, Wientjes J (1971) Peritoneal dialysis for lithium poisoning. BMJ 2:749–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jaeger A, Sauder P, Kopferschmitt J, Tritsch L, Flesch F (1993) When should dialysis be performed in lithium poisoning? A kinetic study in 14 cases of lithium poisoning. J Toxicol Clin Toxicol 31:429–447

    Article  CAS  PubMed  Google Scholar 

  30. Bellomo R, Boyce N (1992) Current approaches to the treatment of severe lithium intoxication. Lithium 3:245–248

    CAS  Google Scholar 

  31. Borrás-Blasco J, Sirvent AE, Navarro-Ruiz A, Murcia-López A, Romero-Crespo I, Enriquez R (2007) Unrecognized delayed toxic lithium peak concentration in an acute poisoning with sustained release lithium product. South Med J 100:321–323

    Article  PubMed  Google Scholar 

  32. Eyer F, Pfab R, Felgenhauer N, Lutz J, Heemann U, Steimer W, Zondler S, Fichtl B, Zilker T (2006) Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychopharmacol 26:325–330

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Leonardo Spatola.

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Spatola, L., Maringhini, S., Canale, C. et al. Lithium poisoning and renal replacement therapy: pathophysiology and current clinical recommendations. Int Urol Nephrol 55, 2501–2505 (2023). https://doi.org/10.1007/s11255-023-03558-5

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