7 - Nefritis intersticial aguda - AEHR · E. Sistémicas Infecciones Síndrome TINU 70 –75% 10...
Transcript of 7 - Nefritis intersticial aguda - AEHR · E. Sistémicas Infecciones Síndrome TINU 70 –75% 10...
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NEFRITISINTERSTICIALAGUDA(NIA)
JavierReque SantivañezHo s p i t a l G e n e r a l U n i v e r s i t a r io d e C a s t e l l ó n
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FRACASORENAL AGUDO
Prerenal Parenquimatoso Postrenal
Necrosistubularaguda Intersticial Glomerulonefritis aguda
85% 5 %10%
NEngl JMed1996;334:1448-1460
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REGISTROESPAÑOLDEBIOPSIASSEN-MADRID2018
Biopsiasporfracasorenalagudo
18a45años
45a65años >65años
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Haas M,SpargoBH,Wit EJ,MeehanSM:Etiologies andoutcome ofacute renalinsufficiency inolder adults:Arenal biopsy study of259cases.AmJKidney Dis 35:433–447,2000
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ETIOLOGÍA
Fármacos E.Autoinmune
E.Sistémicas Infecciones SíndromeTINU
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E.Autoinmune
E.Sistémicas
• Lupuseritematososistémico
• Sarcoidosis
• SíndromeSjögren
• EnfermedadIgG4(2003)• NTIHipocomplementémica(2001)
• Enfermedadporanticuerposantimembrana basaltubular
• Biopsy-proven acute interstitial nephritis,1993-2011:a case series.Muriithi AK,Leung N,Valeri AM,Cornell LD,Sethi S,FidlerME,Nasr SH AmJKidney Dis.2014;64(4):558.• Acute renalfailure ina64-year-oldwhiteman.Paueksakon P,ReveloM,LeeSM,Horn RG,FogoAB AmJKidney Dis.2000;36(3):669.
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Infecciones
A S OC I A DA S C ON N I A
Legionella Poliomavirus
Leptospira Enterococus
Citomegalovirus (CMV) Escherichia coli
Streptococus Adenovirus
Micobacterium tuberculosis Espiroquetas (treponema)
Corinebacterium Diphteriae Hongos (histoplasmosis, coccidiodomicosis)
VirusdeEpstein Barr (EBV) Parásitos(Leishmania,Toxoplasma)
Yersinia
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ETIOLOGÍA
Fármacos E.Autoinmune
E.Sistémicas Infecciones SíndromeTINU
70– 75% 10– 20% 4– 10% 5 – 7%
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Fármacos
ASOC I ADOS C ON N I A
Antiinflamatoriosnoesteroideos(incluidosCOX-2)PenicilinasycefalosporinasRifampicinaSulfonamidasCiprofloxacinoDiuréticos(deasaytiazidas)CimetidinaAlopurinolInhibidoresdebomba deprotonesIndinavir5-aminosalicilatos (Ej.Mesalasina)Inmunomoduladores (iplimumab,nivolumab,pembrolizumab,atezolizumab)
• Drug-Induced Acute Interstitial Nephritis.Moledina DG, Perazella MA. Clin JAmSoc Nephrol. 2017Dec7;12(12):2046-2049• Managing toxicities associatedwithimmune checkpoint inhibitors:consensus recommendations fromtheSociety forImmunotherapy ofCancer (SITC)Toxicity ManagementWorking
Group.JImmunother Cancer. 2017Nov21;5(1):95
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Nat Rev Nephrol. 2018Sep;14(9):571-588.Sury K, Perazella MA, Shirali AC.Cardiorenal complications of immune checkpoint inhibitors.
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Patient Antibiotics PPIs NSAIDs Corticosteroids OtherMedications1 pantoprazole aspirin prednisone albuterol,fluticasone,oxycodone2 hydrocortisone levothyroxine,escitalopram,finesteride,
clonazepam3 linezolid metoprolol,zolpidem,docusate45 trimethoprim/sulfamethox
azolepantoprazole prednisone levothyroxine,enoxaparin
6 omeprazole hydrocortisone levothyroxine,pregabalin,sodiumbicarbonate,fexofenadine,oxycontin,androgel
7 pantoprazole levothyroxine,enoxaparin,maalox,ranitidine8 ibuprofen910 ursodiol,oxycodone, lorazepam,ondansetron1112 ciprofloxacin omeprazole phenazopyridine,quinapril,tramadol,
glucosamine chondroitin
13 omeprazole
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Patogenia
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Manifestacionesclínicas
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Manifestacionesclínicas
• Renalfailure andinterstitial nephritis due topenicillin andmethicillin.BaldwinDS,Levine BB,McCluskey RT,GalloGR.NEngl JMed.1968Dec;279(23):1245-52.
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Manifestacionesclínicas
• Fiebre,rash yeosinofilia.
• Acute interstitial nephritis.AUPragaM,GonzálezE Kidney Int.2010;77(11):956• Duration ofTreatmentwith Corticosteroids andRecovery ofKidney Function inAcute Interstitial Nephritis.Fernandez-Juarez G,Perez JV,SpanishGroup for the Study ofGlomerularDiseases
(GLOSEN).Clin JAmSoc Nephrol.2018Dec 7;13(12):1851-1858.
Manifestación Praga KI20101 Fernandez-JuarezCJASN20182
Fiebre 36% 18%
Rash Cutáneo 22% 8%
Eosinofilia (> 500/mm3) 35% 25%
Fiebre +Rash +Eosinofilia 10% 3%
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Duration ofTreatmentwith Corticosteroids andRecovery ofKidney Function inAcute Interstitial Nephritis.Fernandez-Juarez G,Perez JV,Caravaca-Fontán F,QuintanaL,Shabaka A,RodriguezE,Gadola L,deLorenzoA,CoboMA,Oliet A,SierraM,Cobelo C,IglesiasE,BlascoM,GaleanoC,Cordon A,OlivaJ,PragaM;SpanishGroup for the Study ofGlomerularDiseases (GLOSEN).Clin JAmSoc Nephrol.2018Dec 7;13(12):1851-1858.
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Nat Rev Nephrol. 2010Aug;6(8):461-70.Perazella MA1,Markowitz GS.Drug-induced acute interstitial nephritis.
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(A) Nefritis intersticial inducida por Meticilina(B) Nefritis intersticial por otras drogas(C) Nefritis intersticial por AINEs
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• Acute interstitial nephritis.AUPragaM,GonzálezE Kidney Int.2010;77(11):956.
ManifestacionesFracasorenalagudo 100%
Fracasorenalagudo (diálisis) 40 %
Artralgias 45%
Fiebre 36%
Rash cutáneo 22%
Eosinofilia 35%
Microhematuria 67%
Macrohematuria 5%
Leucocituria 82 %
Proteinurianonefrótica 93 %
Proteinurianefrótica 2,5%
Síndrome nefrótico 0,8%
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¿Eosinofiluria?
Clin J Am Soc Nephrol 8: 1857–1862, 2013
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Tiempodeinicio:
• 3a5días– Segundaexposiciónalfármaco
• Semanasameses- Primeraexposiciónalfármaco
BrJClinPharmacol.2007Dec;64(6):819–823.
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Patología
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Granuloma
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Tratamiento
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Tratamiento
•Discontinuacióndelfármaco
•Corticoides
•Otros
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Tratamiento
Duration ofTreatmentwith Corticosteroids andRecovery ofKidney Function inAcute Interstitial Nephritis.Fernandez-Juarez G,Perez JV,SpanishGroup for the Study ofGlomerularDiseases(GLOSEN).Clin JAmSoc Nephrol.2018Dec 7;13(12):1851-1858.
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• Lamayoríadeloscasosdenefritisintersticialsonreaccionesalérgicas:• Soninducidasporfármacos• No esfenómenodosisdependiente• Sólounpequeñoporcentajedelospacientesdesarrollalaenfermedad• Remisióntrasdiscontinuacióndelfármaco• Remiteconlareutilizacióndelmismofármacoyunosimilar
• LoslinfocitosTjueganunpapelfundamentalenlaetiopatogenia:• Tiempode10a14días(síndromesmediadosporcélulasT)• ElinfiltradointersticialestácompuestoporlinfocitosT• EltestdeestimulacióndelinfocitosTespositivoenlamayoríadelospacientes.
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Drug-specificproliferationofpatientsPBMC
Pt 1.
Positive proliferative response of PBMC to flucloxacillin
Pt 2
PBMC proliferative response to penicillin G
Pt 3
PBMC proliferative response to disulfiram
Involvement of Drug-Specific T cells in Acute Drug-Induced Interstitial Nephritis Spanou et al, JASN, 17: 2919, 2006
#Even though there were multi drug exposure, each patient elicited proliferative response to only one drug
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Duration ofTreatmentwith Corticosteroids andRecovery ofKidney Function inAcute Interstitial Nephritis.Fernandez-Juarez G,Perez JV,SpanishGroup for the Study ofGlomerularDiseases (GLOSEN).Clin JAmSoc Nephrol.2018Dec 7;13(12):1851-1858.
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Parallevaracasa:• La N IA d eb e fo rma r p a r t e d e l d i a gn ó s t i co d i f e r en c i a l d e t od o pa c i e n t e con
f r a ca s o r en a l a gu d o .
• C u a l q u i e r f á rma co p u ed e ca u s a r N IA , d eb e p r e s t a r s e e s p e c i a l a t e n c i ó n a
a n t i b i ó t i co s , a n t i n f l ama t o r i o s n o e s t e r o i d eo s e i n h i b i d o r e s d e b omba d e
p r o t o n e s .
• La t r i a d a c l á s i c a ( f i e b r e , r a s h y e o s i n o f i l i a ) e s mu y i n f r e cu en t e
• E l t i empo d e s d e e l i n i c i o d e l f á rma co h a s t a e l i n i c i o d e l cu a d ro e s mu y va r i a b l e
• E l u s o d e co r t i co i d e s ( p r e co z ) s e a s o c i a a me j o r p r o n ó s t i co
• C o n l a e v i d en c i a q u e d i s p o n emo s a c t u a lmen t e :
• Lo s b o l o s p o d r í a n NO s e r n e ce s a r i o s
• E l t r a t am i en t o e s t e r o i d eo n o d eb e r í a d u r a r ma s d e 1 2 s eman a s .
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Muchasgracias…
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