F. Stucker, Néphrologie, HUG - Nephroblog · PDF fileF. Stucker, Néphrologie,...
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F. Stucker, Néphrologie, HUG
Grünfeld JP, Rossier B.C. Lithium nephrotoxicity revisited. Nat Rev Nephrol 5, 270-6 (2009)
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Un traitement historique…
II BC
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Un traitement historique…
II BC
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Un traitement historique…
Traitement de la goutte
Complément alimentaire
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Retrait du marché par la FDA
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Cation monovalent
Faible liaison aux protéines plasm.
VD <1l/kg
Image NephroHUG
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CAVE !!!
Aigu chronique
Accumulation tissulaire dans traitement chronique
T1/2 aigu 12-27h
T1/2 chronique >60h
Image NephroHUG
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Librement filtré (GFR)
GFR, filtration
Donc accumulation
Image NephroHUG
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Librement filtré (GFR)
Réabsorbé (80%) TP
CAVE : hypovolémie
réabsorption
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Cation monovalent
Librement filtré (GFR)
Réabsorbé (80%) TP
Petite réabsorption distale (ENaC)
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Pic pl 1-2h (4h si retard)
95% d’excrétion rénale
1ère phase 6-12h
2ème phase 14j (relargage tissulaire)
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Adaptation des doses (Drug Dosage in Kidney Disease, Gunter Seffart,
2011 by Dustri-verlag Dr Karl Feistle GmbH & Co. KG. Munich Orlando)
Dosage reduction:CKD stage 3: reduce 20-50%CKD stage 4: reduce 50-75 %.CKD stage 5 non in dialysis: avoid because of unpredictable renal excretion and risk of intoxication.CKD stage 5 on hemodialysis: Removal by Hemodialysis is substantial and usual dosage should be given after each HD treatment and dosage between
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Toxicité (s) rénale (s)
-Dysfonctions tubulaires (diabète insipide néphrogène +/-hyperNa, natriurèse, acidose métabolique)
-Insuffisance rénale chronique
-Hypercalcémie
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1a. Diabète insipide néphrogène
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Avec autorisation JP Grünfeld
La cellule principale du tube collecteur
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Lithium réabsorption d’H2O diabète insipide
Bedford J et al. Lithium-induced Nephrogenic Diabetes Insipidus:renal effects of Amiloride. cJASN 3:1324-1331, 2008.
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amiloride
+ thiazides , évt AINS….
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� Stimulation non-osmotique de la vasopressine
� Augmentation expression AQP-2COX-2
Kim GH et al. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. JASN 2004 Nov;15(11):2836-43
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� PGE2 antagonise l’action de l’ADH:� Réabsorption H2O tube collecteur (inhibition
synthèse cAMP)� Réabsorption NaCl anse ascendante épaisse de
Henlé
� ↓ production de PG:� ↓ filtration glomérulaire� expression AQP2
� Action rapide� Indométhacine 3x50mg/j
Kim et al Am J Physiol Renal Physiol 2008
COX-2
Dia : K Hadaya
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1b. Natriurèse augmentée
Modification de la régulation EnaC ? Diminution de la sensibilité àl’aldostérone ?
1c. Acidose métabolique
Via probable diminution de la capacité de sécrétion de protons
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2. Insuffisance rénale chronique
Apparaît après 15-20 ans de traitement
Atteinte principalement interstitielle
Mais également glomérulaire (MCD>FSGS)
Progression lente (2ml/min/an) (Presne C. Lithium-induced nephropathy: rate of progression
and pronostic factors. Kidney Int. 64, 585-592 (2003).
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Figure 1c. MR images in a 57-year-old man.
Farres M T et al. Radiology 2003;229:570-574
©2003 by Radiological Society of North America
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2. Insuffisance rénale chronique
Traitement :
Arrêt lithium ?Point de non-retour….
Amiloride ?
Contrôle TA
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3. Hypercalcémie
Via interférence avec calcium sensing receptor
Modification du seuil de sécrétion de la PTH
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Intoxication aiguë : HYDRATATION ! Arrêt néphrotoxiques
Indications à la dialyse: (pas de consensus clair….)
Symptômes sévères neurologiques : coma, épilepsie, léthargie, cardiaquesinsuffisance rénale, troubles électrolytiques majeurscontre-indication à l’hydratation
Taux sériques très élevés (> 2.5 mmol/l ?)
Waring WS, Management of lithium toxicity, Toxicol Rev. 2006;25(4):221-30.
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INTOXICATION AIGUE : HYDRATATION ! Arrêt néphrotoxiques
Indications à la dialyse: (pas de consensus clair….)
Symptômes sévères neurologiques : coma, épilepsie, léthargie, cardiaquescontre-indication à l’hydratation
Taux sériques très élevés ?
CAVE +++
TAUX SERIQUES MAL CORRELES A LA TOXICITE (accumulation tissulaire)
LA CLINIQUE PRIME !!!