Nephrotoxizität und Langzeitbehandlung mit Lithium

 

 Buy Article Permissions and Reprints

Zusammenfassung

In der systematischen Übersichtsarbeit werden die verfügbaren Daten zu nephrotoxischen Effekten einer Langzeitbehandlung mit Lithium unter besonderer Berücksichtigung klinischer, pathophysiologischer und epidemiologischer Aspekte dargestellt. Lithium kann zu tubulärer Dysfunktion (nephrogener Diabetes insipidus, hyperchlorämische metabolische Azidose, vermehrte Natriurese) und lithiuminduzierter Nephropathie (LIN) mit eingeschränkter glomerulärer Filtrationsrate führen. Für das Vorgehen bei LIN unter laufender Lithiumbehandlung existieren gegenwärtig keine Leitlinien, sodass im Hinblick auf die Fortsetzung der Lithiumbehandlung jeweils eine individuelle Nutzen-Risiko-Bewertung erfolgen muss.

Abstract

With particular focus on clinical, pathophysiologic and epidemiologic aspects this systematic review article presents the available data on nephrotoxic effects of a long-term treatment with lithium. Lithium may lead to tubular dysfunction (LITD = nephrogenic diabetes insipidus, hyperchloremic metabolic acidosis, increased natriuresis) and lithium-induced nephropathy (LIN) with reduced glomerular filtration rate (GFR). The histopathologic finding of LIN is chronic tubulo-interstitial nephritis. LITD frequently presents with polydipsia/-uria and reduced urine osmolality, while LIN features a wide clinical spectrum ranging from clinically asymptomatic presentations with reduced GFR to end-stage renal failure. LIN seems to feature slow progression and is significantly less frequent than LITD. Regular monitoring of renal function is indispensable for patients treated with lithium. Patients with reduced GFR under treatment with lithium should always be presented to a nephrologist. Currently, there are no guidelines for the handling of patients with LIN and ongoing treatment with lithium. Thus, regarding continuation of lithium-treatment an individual benefit/risk assessment is necessary.

• Literatur

• 1 Johnson F. The history of lithium therapy. London: Macmillan; 1984
  Google Scholar
• 2 Garrod A. The nature and treatment of gout and rheumatic gout. London: Walton; 1859
  Google Scholar
• 3 Parker G. John Cade. Am J Psychiatry 2012; 169: 125-126
  CrossrefPubMedGoogle Scholar
• 4 Mitchell S. On the use of bromide of lithium. Am J Med Sci 1877; 60: 443-445
  PubMedGoogle Scholar
• 5 Mitchell S. Clinical lecture on nervousness in the male. Med News 1877; 35: 177-184
  PubMedGoogle Scholar
• 6 Hammond W. A treatise on diseases of the nervous system. New York: Appleton; 1871
  Google Scholar
• 7 Schioldann J. The Lange theory of “periodical depressions”. Adelaide: Adelaide Academic Press; 2001
  Google Scholar
• 8 Schou M, Juel-Nielsen N, Strömgren E et al. The treatment of manic psychoses by the administration of lithium salts. J Neurol Neurosurg Psychiatr 1954; 17: 250-260
  CrossrefPubMedGoogle Scholar
• 9 Cipriani A, Barbui C, Salanti G et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 2011; 378: 1306-1315
  CrossrefPubMedGoogle Scholar
• 10 Geddes J, Burgess S, Hawton K et al. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry 2004; 161: 217-222
  CrossrefPubMedGoogle Scholar
• 11 Burgess S, Geddes J, Hawton K et al. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev 2001; CD003013
  PubMedGoogle Scholar
• 12 Cipriani A, Smith K, Burgess S et al. Lithium versus antidepressants in the long-term treatment of uniplar affective disorder. Cochrane Database Syst Rev 2006; CD003492
  PubMedGoogle Scholar
• 13 Bauer M, Adli M, Baethge C et al. Lithium augementation therapy in refractory depression: clinical evidence and neurobiological mechanisms. Can J Psychiatry 2003; 48: 440-448
  PubMedGoogle Scholar
• 14 Tondo L, Hennen J, Baldessarini R. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand 2001; 104: 163-172
  CrossrefPubMedGoogle Scholar
• 15 Cipriani A, Pretty H, Hawton K et al. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry 2005; 162: 1805-1819
  CrossrefPubMedGoogle Scholar
• 16 Müller-Oerlinghausen B, Felber W, Berghöfer A et al. The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients. Arch Suicide Res 2005; 9: 307-319
  CrossrefPubMedGoogle Scholar
• 17 DGBS, DGPPN. S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen. 2012. Langversion (Mai). Im Internet: http://www.dgppn.de/fileadmin/user_upload/_medien/download/pdf/kurzversion-leitlinien/s3-leitlinie-bipolar.pdf (Stand: 30.07.2013)
  Google Scholar
• 18 Rote Liste 2011 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Frankfurt/Main: Rote Liste Service GmbH; 2011
  Google Scholar
• 19 Lombardi G, Panza N, Biondi D et al. Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study. J Endocrinol Invest 1993; 16: 259-263
  PubMedGoogle Scholar
• 20 Kusalic M, Engelsmann F. Effect of lithium maintenance therapy on thyroid and parathyroid function. J Psychiatry Neurosci 1999; 24: 227-233
  PubMedGoogle Scholar
• 21 Malhi G, Tanious M, Das P et al. The science and practice of lithium therapy. Aust N Z J Psychiatry 2012; 46: 192-211
  CrossrefPubMedGoogle Scholar
• 22 Bowden C, Calabrese J, Ketter T et al. Impact of lamotrigine and lithium on weight in obese an nonobese patients with bipolar I disorder. Am J Psychiatry 2006; 163: 1199-1201
  CrossrefPubMedGoogle Scholar
• 23 Sachs G, Bowden C, Calabrese J et al. Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disord 2006; 8: 175-181
  CrossrefPubMedGoogle Scholar
• 24 Keck P, McElroy S. Bipolar disorder, obesity, and pharmacotherapy-associated weight gain. J Clin Psychiatry 2003; 64: 1426-1435
  CrossrefPubMedGoogle Scholar
• 25 Timmer R, Sands J. Lithium intoxication. J Am Soc Nephrol 1999; 10: 666-674
  CrossrefPubMedGoogle Scholar
• 26 Hsu C, Liu P, Chen J et al. Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology 2005; 103: 101-106
  CrossrefPubMedGoogle Scholar
• 27 Roose S, Nurnberger J, Dunner D et al. Cardiac sinus node dysfunction during lithium treatment. Am J Psychiatry 1979; 136: 804-806
  PubMedGoogle Scholar
• 28 Chang Y, Lin H, Deng H. Subclinical lithium neurotoxicity: correlation of neural conduction abnormalities and serum lithium level in manic-depressive patients with lithium treatment. Acta Neurol Scand 1990; 82: 82-86
  PubMedGoogle Scholar
• 29 Adityanjee MBBS, Munshi K, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol 2005; 28: 38-49
  CrossrefPubMedGoogle Scholar
• 30 Fountoulakis K, Vieta E, Bouras C et al. A systematic review of existing data on long-term lithium therapy: neuroprotective or neurotoxic?. Int J Neuropsychopharmacol 2008; 11: 269-287
  PubMedGoogle Scholar
• 31 Lydiard R, Gelenberg A. Hazards and adverse effects of lithium. Ann Rev Med 1982; 33: 327-344
  CrossrefPubMedGoogle Scholar
• 32 Kropf D, Müller-Oerlinghausen B. Changes in learning, memory, and mood during lithium treatment. Approach to a research strategy. Acta Psychiatr Scand 1979; 59: 97-124
  CrossrefPubMedGoogle Scholar
• 33 Grandjean E, Aubry J. Lithium: updated human knowledge using an evidence-based approach: Part II: clinical pharmacology and therapeutic monitoring. CNS Drugs 2009; 23: 331-349
  CrossrefPubMedGoogle Scholar
• 34 Wingo A, Wingo T, Harvey P et al. Effects of lithium on cognitive performance: a meta-analysis. J Clin Psychiatry 2009; 70: 1588-1597
  CrossrefPubMedGoogle Scholar
• 35 Grünfeld J, Rossier B. Lithium nephrotoxicity revisited. Nat Rev Nephrol 2009; 5: 270-276
  CrossrefPubMedGoogle Scholar
• 36 Finley P, Warner M, Peabody C. Clinical relevance of drug interactions with lithium. Clin Pharmacokinet 1995; 29: 172-191
  CrossrefPubMedGoogle Scholar
• 37 Llewellyn A, Stowe Z, Strader JJ. The use of lithium and management of woman with bipolar disorder during pregnancy and lactation. J Clin Psychiatry 1998; 53 (Suppl. 06) 57-65
  PubMedGoogle Scholar
• 38 Eastham J, Jeste D, Young R. Assessment and treatment of bipolar disorder in the elderly. Drugs Aging 1998; 12: 205-224
  CrossrefPubMedGoogle Scholar
• 39 Rej S, Herrmann N, Shulman K. The effects of lithium on renal function in older adults – a systematic review. J Ger Psychiatry 2012; 25: 51-61
  PubMedGoogle Scholar
• 40 Fyro B, Pettersson U, Sedvall G. Serum lithium levels and side effects during administration of lithium carbonate and two slow release lithium preparations to human volunteers. Pharmacologia Clinica 1970; 2: 236-240
  CrossrefPubMedGoogle Scholar
• 41 Gitlin M. Lithium and the kidney – an updated review. Drug Safety 1999; 20: 231-243
  CrossrefPubMedGoogle Scholar
• 42 Sproule B, Hardy B, Shulman K. Differential pharmakokinetics of lithium in elderly patients. Drugs Aging 2000; 16: 165-177
  CrossrefPubMedGoogle Scholar
• 43 Eyer F, Pfab R, Felgenhauer N et al. Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychoparmacol 2006; 26: 325-330
  PubMedGoogle Scholar
• 44 Hundley J, Woodrum D, Saunders B et al. Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring. Surgery 2005; 138: 1027-1031
  CrossrefPubMedGoogle Scholar
• 45 Bedford J, Weggery S, Ellis G et al. Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. Clin J Am Soc Nephrol 2008; 3: 1324-1331
  CrossrefPubMedGoogle Scholar
• 46 Bendz H, Aurell M. Drug-induced diabetes insipidus: incidence, prevention and management. Drug Safety 1999; 21: 449-456
  CrossrefPubMedGoogle Scholar
• 47 Walker R, Weggery S, Bedford J et al. Lithium-induced reduction in urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion in healthy volunteers. Kidney Int 2005; 67: 291-294
  CrossrefPubMedGoogle Scholar
• 48 Marples D, Christensen S, Christensen E et al. Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 1995; 95: 1838-1845
  CrossrefPubMedGoogle Scholar
• 49 Laursen U, Pihakaski-Maunsbach K, Kwon T et al. Changes of rat kidney AQP2 and Na,K-ATPase mRNA expression in lithium-induced nephrogenic diabetes insipidus. Nephron Exp Nephrol 2004; 97: e1-16
  CrossrefPubMedGoogle Scholar
• 50 Kim Y, Kwon T, Christensen B et al. Altered expression of renal acid-base transporters in rats with lithium-induced NDI. Am J Physiol Renal Physiol 2003; 285: F1244-1257
  PubMedGoogle Scholar
• 51 Christensen B, Marples D, Kim Y et al. Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI. Am J Physiol Cell Physiol 2004; 286: C952-964
  CrossrefPubMedGoogle Scholar
• 52 Nielsen J, Kwon T, Praetorius J et al. Segment-specific ENaC downregulation in kidney of rats with lithium-induced NDI. Am J Physiol Renal Physiol 2003; 285: F1198-1209
  PubMedGoogle Scholar
• 53 Nielsen J, Kwon T, Frøkiaer J et al. Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD. Am J Physiol Renal Physiol 2006; 290: F1222-1233
  PubMedGoogle Scholar
• 54 Christensen B, Loffing J, Hummler E et al. Collecting duct-specific gene inactivation of α ENaC protects mice against lithium-induced nephrogenic diabetes insipidus. J Am Soc Nephrol 2006; 17: 295A
  PubMedGoogle Scholar
• 55 Galizia L, Marino G, Kotsias B. Lithium and its relation with the epithelial sodium channel and aquaporin-2. Medicine (B Aires) 2012; 72: 171-175
  PubMedGoogle Scholar
• 56 Rojek A, Nielsen J, Brooks H et al. Altered expression of selected genes in kidney of rats with lithium-induced NDI. Am J Physiol Renal Physiol 2005; 288: F1276-1289
  CrossrefPubMedGoogle Scholar
• 57 Rao R, Zhang M, Zhao M et al. Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria. Am J Physiol Renal Physiol 2005; 288: F642-649
  PubMedGoogle Scholar
• 58 Kotnik P, Nielsen J, Kwon T et al. Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus. Am J Physiol Renal Physiol 2005; 288: F1053-1068
  CrossrefPubMedGoogle Scholar
• 59 Li Y, Shaw S, Kamsteeg E et al. Development of lithium-induced nephrogenic diabetes insipidus is dissociated from adenylyl cyclase activity. J Am Soc Nephrol 2006; 17: 1063-1072
  CrossrefPubMedGoogle Scholar
• 60 Bedford J, Leader J, Jing R et al. Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 2008; 294: F812-820
  CrossrefPubMedGoogle Scholar
• 61 Batlle D, von Riotte A, Gaviria M et al. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med 1985; 312: 408-414
  CrossrefPubMedGoogle Scholar
• 62 Hestbech J, Hansen H, Amdisen A et al. Chronic renal lesions following long-term treatment with lithium. Kidney Int 1977; 12: 205-213
  CrossrefPubMedGoogle Scholar
• 63 Markowitz G, Radhakrishnan J, Kambham N et al. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol 2000; 11: 1439-1448
  PubMedGoogle Scholar
• 64 Presne C, Fakhouri F, Noël L et al. Lithium-induced nephropathy: Rate of progression and prognostic factors. Kidney Int 2003; 64: 585-592
  CrossrefPubMedGoogle Scholar
• 65 Farres M, Ronco P, Saadoun D et al. Chronic lithium nephropathy: MR imaging for diagnosis. Radiology 2003; 229: 570-574
  CrossrefPubMedGoogle Scholar
• 66 Santella R, Rimmer J, MacPherson B. Focal segmental glomerulosclerosis in patients receiving lithium carbonate. Am J Med Sci 1988; 84: 951-954
  CrossrefPubMedGoogle Scholar
• 67 Johnson G. Lithium – early development, toxicity, and renal function. Neuropsychopharmacology 1998; 19: 200-205
  CrossrefPubMedGoogle Scholar
• 68 Freeman M, Freeman S. Lithium: clinical considerations in internal medicine. Am J Med Sci 2006; 119: 478-481
  CrossrefPubMedGoogle Scholar
• 69 Bendz H, Sjödin I, Aurell M. Renal function on and off lithium in patients treated with lithium for 15 years or more. A controlled, prospective lithium-withdrawal study. Nephrol Dial Transplant 1996; 11: 457-460
  CrossrefPubMedGoogle Scholar
• 70 Muir A, Davidson R, Silverstone T et al. Two regimens of lithium prophylaxis and renal function. Acta Psychiatr Scand 1989; 80: 579-583
  CrossrefPubMedGoogle Scholar
• 71 Quiroz J, Gould T, Manji H. Molecular effects of lithium. Mol Interv 2004; 4: 259-272
  CrossrefPubMedGoogle Scholar
• 72 Boton R, Gaviria M, Battle D. Prevalance, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis 1987; 10: 329-345
  PubMedGoogle Scholar
• 73 Stone K. Lithium-induced nephrogenic diabetes insipidus. J Am Board Fam Prac 1999; 12: 43-47
  PubMedGoogle Scholar
• 74 Giles P, Fitzmaurice D. Formula estimation of glomerular filtration rate: have we gone wrong?. BMJ 2007; 334: 1198-1200
  CrossrefPubMedGoogle Scholar
• 75 Stevens L, Zhang Y, Schmid C. Evaluating the performance of equations for estimating glomerular filtration rate. J Nephrol 2008; 21: 797-807
  PubMedGoogle Scholar
• 76 Bassilios N, Martel P, Godard V et al. Monitoring of glomerular filtration rate in lithium-treated outpatients – an ambulatory laboratory database surveillance. Nephrol Dial Transplant 2008; 23: 562-565
  PubMedGoogle Scholar
• 77 Lokkegaard H, Andersen N, Henriksen E et al. Renal function in 153 manic-depressive patients treated with lithium for more than five years. Acta Psychiatr Scand 1985; 71: 347-355
  CrossrefPubMedGoogle Scholar
• 78 Waller D, Edwards J, Papasthatis-Papayanni S. A longitudinal assessment of renal function during treatment with lithium. Q J Med 1988; 68: 553-558
  PubMedGoogle Scholar
• 79 Schou M, Vestergaard P. Prospective studies on a lithium cohort. 2. Renal function. Water and electrolyte metabolism. Acta Psychiatr Scand 1988; 78: 427-433
  CrossrefPubMedGoogle Scholar
• 80 Povlsen U, Hetmar O, Ladefoged J et al. Kidney functioning during lithium treatment: a prospective study of patients treated with lithium for up to ten years. Acta Psychiatr Scand 1992; 85: 56-60
  CrossrefPubMedGoogle Scholar
• 81 DePaulo JJ, Correa E, Sapir D. Renal function and lithium: a longitudinal study. Am J Psychiatry 1986; 143: 892-895
  PubMedGoogle Scholar
• 82 Smigan L, Bucht G, von Knorring L et al. Long-term lithium treatment and renal functions. A prospective study. Neuropsychobiology 1984; 11: 33-38
  CrossrefPubMedGoogle Scholar
• 83 Kallner G, Petterson U. Renal, thyroid and parathyroid functioning during lithium treatment: laboratory tests in 207 people treated for 1-30 years. Acta Psychiatr Scand 1995; 91: 48-51
  CrossrefPubMedGoogle Scholar
• 84 Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord 2010; 126: 436-440
  CrossrefPubMedGoogle Scholar
• 85 Janowsky D, Soares J, Hatch J et al. Lithium effect on renal glomerular function in individuals with intellectual disability. J Clin Psychopharmacol 2009; 29: 296-299
  CrossrefPubMedGoogle Scholar
• 86 Bendz H, Schön S, Attman P et al. Renal failure occurs in chronic lithium treatment but is uncommon. Kidney Int 2010; 77: 219-224
  CrossrefPubMedGoogle Scholar
• 87 Bendz H, Aurell M, Balldin J et al. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant 1994; 9: 1250-1254
  PubMedGoogle Scholar
• 88 Bendz H, Andersch S, Aurell M. Kidney function in an unselected lithium population. A cross-sectional study. Acta Psychiatr Scand 1983; 68: 325-334
  CrossrefPubMedGoogle Scholar
• 89 Janowsky D, Buneviciute J, Hu Q et al. Lithium-induced renal insufficiency: a longitudinal study of creatinine increases in intellectual disabled adults. J Clin Psychoparmacol 2011; 31: 769-773
  PubMedGoogle Scholar
• 90 McKnight R, Adida M, Budge K et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet 2012; 379: 721-728
  CrossrefPubMedGoogle Scholar
• 91 Alexander M, Farag Y, Mittal B et al. Lithium toxicity: a double-edged sword. Kidney Int 2008; 73: 233-237
  CrossrefPubMedGoogle Scholar
• 92 Ibekken C, Becker J, Baumgärtel M. Renal side effects of long-term lithium therapy. Dtsch Med Wochenschr 2012; 137: 143-148
  Article in Thieme ConnectPubMedGoogle Scholar
• 93 DGPPN, BÄK, KBV et al. S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression-Langfassung Januar 2012, Version 1.3. Berlin, Düsseldorf: DGPPN, AZQ, AWMF; 2009
  Google Scholar
• 94 AWMF. Leitlinien für Diagnostik und Therapie in der Neurologie: Clusterkopfschmerz und trigeminoautonome Kopfschmerzen. Stuttgart: Georg Thieme Verlag; 2008
  Google Scholar
• 95 Belmaker R. Bipolar disorder. N Engl J Med 2004; 351: 476-486
  CrossrefPubMedGoogle Scholar