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Cockcroft-Gault equation
MDRD Equation
T#!%#2)%#(!-.+!.%!1#%!61(#%!01#2)(#+!*+#%/+!.%!-)*-%!P3;<P3=!47U5E!5)!
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The Cockcroft-Gault equation allows the creatinine clearance to
be estimated from the serum creatinine in a patient with a stable
-/+%*%#-+!5+//%!-*+%')#)#%!)#!*+/%2)(#+!%!4%&&%!-(*$(*+%3!-*+%')#)#%!&)+*)-%!+5!
serum creatinine:
NKF's KDOQI
+'>8! clinical practice guidelines recommend the
Modification(140
of -Diet
age) xinlean
Renal Disease
body weight [kg]
CCr (mL/min) =
(MDRD) Study equation
Cr [mg/dL] tox 72estimate GFR
!
T#B%/'+*#%'),%!?!/%!X_`_G!
This formula takes into account the increase in creatinine
GFR, in mL/min
production per 1.73 weight,
with increasing m2 = 175 andxthe
SCr (exp[-1.154])
decline X
in creatinine
production with age. For women, multiplication by 0.85 is
required
Age to account for smaller
(exp[-0.203]) X (0.742muscle massxcompared
if female) to men.
(1.21 if black)
!
The equation is not adjusted for body surface area. Therefore to
! compare normal values, the calculation should be adjusted for
body
w surface area. Normalization for body surface increases the
ww.kidney.org/professionals/KLS/gfr_calculator.cfm
E%!-'0#"#'*");)?!&'%'%!$*($(&'%!-(4+!$%*%4+'*(!$+*!,%/1'%*+!/%!01#2)(#+!*+#%/+!)#!
accuracy of this equation, particularly among those with
nephron.com/mdrd/default.html
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decreased renal function.
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The commonly utilized estimation equations are less accurate in individuals
#+//%!$($(/%2)(#+Z3!4+#'*+!&+46*%!+&&+*+!&1$+*)(*+!%//%!-*+%')#)#%!#+//%!,%/1'%2)(#+!5+/!
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with normal GFR, children, elderly patients, specific ethnic groups, pregnant
women, and those with unusual muscle mass, body habitus, and weight.
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Sindromi nefrologiche
<'*3,$/')=(+,$%$&'-.()

Insufficienza renale acuta Insufficienza renale


rapidamente progressiva
Sedimento negativo
Assenza di proteine
Microalbuminuria
Proteinuria
Ematuria
Sindrome Nefrosica
Sindrome Nefritica

Insufficienza renale cronica Funzione normale


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Common Causes of Glomerular Proteinuria
Cause Renal Manifestation Clinical Presentation Laboratory/Imaging
Diabetes mellitus type 1/type 2 Ranging from microalbuminuria to nephrotic Polyuria, polydipsia, nocturia, Fasting plasma glucose 126 mg/dL (7.0
range proteinuria; most common etiology of weight loss mmol/L). Increased HbA1c.
end-stage renal disease in the US
Hypertension Microalbuminuria Often asymptomatic (excluding Other possible signs of hypertensive
hypertensive crisis)! injury
Crescentic glomerulonephritis *Proteinuria with an active urinary sediment and Sign or symptoms of uremia Increased creatinine and BUN levels.
decreased GFR Hypertension. ANCA and anti-GBM
antibodies
Multiple myeloma SCr is increased in 50% of patients15; urine Pallor, radiculopathy, peripheral Monoclonal protein in serum and/or
protein is not detected on urine dipstick; neuropathy, bone pain in the back protein electrophoresis, lytic lesions
sulfosalicylic acid test and UPCR detect or chest is present in 60% of and fractures on x-ray, hypercalcemia
proteinuria patients27
Light chain deposition disease Most commonly associated with multiple Related to renal, cardiac, or Tissue deposition of kappa light chains,
myeloma; in rare cases it is occurs with hepatic involvement urinary light chain excretion
lymphoma
Primary amyloidosis Nephrotic syndrome with or without renal Peripheral neuropathy, Amyloid deposition on biopsy;
insufficiency macroglossia, hepatomegaly evidence of a clonal plasma cell
proliferative disorder
HIV nephropathy Nephrotic syndrome, slowly progressive renal More common in African- HIV positive
dysfunction American patients; edema
Immunoglobulin A nephropathy From urine abnormalities to nephritic syndrome Hematuria Renal immunoglobulin A deposition;
active urine sediment
Minimal change disease, FSGS Nephrotic syndrome Edema, anasarca, foamy urine Hypercholesterinemia,
membranous glomerulonephritis hypoalbuminemia, proteinuria;
diagnostic renal biopsy findings
Streptococcal glomerulonephritis Ranging from microscopic hematuria to acute Recurrent episodes of hematuria Kidney biopsy shows proliferative
nephritic syndrome glomerulonephritis
Other forms of glomerulonephritis, Proteinuria with or without an active urinary Depending on underlying disease ANA, complement C3 and C4, VDRL,
infectious or systemic diseases sediment (red blood cell casts, dysmorphic hepatitis serology, cryoglobulins
erythrocytes)!

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< Proteineplasmatiche
Proteine plasmatiche
<#"#$)3')'6(,-$"&1%"C'%'#:)

nella sindrome
nella sindromenefrosica nefrosica
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< transferrina !
< transferrina
<< albumina
albumina < transcortina
< transcortina !
<< !1
!1 globuline
globuline
< TGB,
< TGB, < T4
< T4
>> !2
!2 ee " globuline
globuline
< vitamin D-binding protein
< vitamin D-binding protein!
Immunoglobuline
Immunoglobuline Complemento
Complemento
<< IgG
IgG
< fattore B B !
+/- >> IgA, < fattore
+/- IgA, IgM,
IgM,IgEIgE < C3, C4bp
< proteine di trasporto < C3, C4bp !
< proteine di trasporto < C1q, C2, C8,C8,
Ci Ci
dei metalli
metalli (Fe, < C1q, C2,
dei (Fe,Cu,
Cu,Zn)
Zn) < C4
< eritropoietina < C4 !
< eritropoietina >/- C1s, C4, inibitore di C1
>/- C1s, C4, inibitore di C1
!

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$%2)+#'+!4%!$(&&(#(!%#-.+!$*+,%/+*+!/B1#%!&1//B%/'*%8!H+*!+&+4$)(3!#+)!$%2)+#')!)#!-1)!-B?!
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$%'(/(7)%3!&)!.%!1#%!&)'1%2)(#+!5)!'6(,7$%(/'"!-.+!$*+,%/+!&1//%!*)512)(#+!5+//%!
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$*+,%/+#'+4+#'+8!"#!:1+&')!$%2)+#')!/B1&(!5+)!5)1*+')-)!#(#!-(4$(*'%!7*(&&)!$*(6/+4)8!
b+)!$%2)+#')!-(#!$*+,%/+#2%!5+//%!*)512)(#+!5+//%!$*+&&)(#+!(#-(')-%3!/%!&)'1%2)(#+!?!
)#,+-+!:1+//%!5)!)$(,(/+4)%3!+!/B%''),%2)(#+!5+)!&)&'+4)!5)!-(4$+#&(!&(5)(<*)'+#'),)!?!1#%!

Diagnosi
-$*0(&1(*2")3(%%51*3(,+'%%'*&G!%//(*%3!)!5)1*+')-)!5+,(#(!+&&+*+!)4$)+7%')!-(#!-%1'+/%!+!
$*+,)%!+&$%#&)(#+!$/%&4%')-%!($$(*'1#%8!L1+&')!$%2)+#')!.%##(!6%&&)!/),+//)!5)!MbH8)

I pazienti con overflow (aumentato volume intravascolare) sono pi spesso


quelli con funzione renale ridotta (<50% del normale), una concentrazione
plasmatica di albumina > 2 g/dl ed ipertensione. Sono pi spesso affetti da GN
membranosa o glomerulosclerosi focale e segmentale.
Riduzione del
filtrato
Infiltrato infiammatorio glomerulare Ritenzione
Secrezione di
tubulo-interstiziale angiotensina II primitiva
Aumentato di sodio
riassorbimento
di sodio

Ipoalbuminemia
Perdita di albumina Ridotta
con le urine Edema Ritenzione di sodio
pressione oncotica
Soppressione della
sintesi epatica di albumina

I pazienti con componente da underfilling (ridotto volume plasmatico) sono


quelli con funzione renale normale o di poco ridotta, ipoalbuminemia grave
(spesso <1 g/dl) e a rapida insorgenza Sono pi spesso affetti da malattia a
lesioni minime. !
`)&-.)!5+//B+5+4%!5%!1#5+*0)//)#7G!

< O.(-]!)$(,(/+4)-(!
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'+#5+!%5!%14+#'%*+!/%!&)#'+&)!5)!%$(/)$($*('+)#+!5)!')$(!hE_E!+!*%//+#'%!)/!-%'%6(/)&4(!
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Sindrome Nefrosica
Proteinuria > 3.5 g nelle 24 ore, accompagnata da edema,
-(%71/%2)(#+!%14+#'%3!4+#'*+!,+#7(#(!$+*&)!-(#!/+!1*)#+!)!0%''(*)!)#)6)'(*)!0)&)(/(7)-)!
ipoalbuminemia (<2,5 g/dl), iperlipidemia and lipiduria.
5+//%!-%&-%'%!-(%71/%'),%3!-(#!-(#&+71+#'+!&'%'(!6,$#,$/C$#'-$8
Perdita di IgG e di Proteinuria Perdita della globulina
complemento legante il colecalciferolo

Infezioni Sintesi VLDL Iperparatiroidismo


Catabolismo LDL secondario
Perdita fattori regolatori
Perdita di inibitori
della coagulazione
Osteomalacia
Sintesi epatica di fattori
della coagulazione e piastrine Osteite Fibrosa
Aterosclerosi
Edema
Ipercoagulabilit

Trombosi
Embolia Polmonare Instabilit cardiovascolare
!
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*+#%/+!(!(&'+)'+!0)6*(&%8!!

Sindrome nefrosica - cause


"#(/'*+3!&)!.%!/%!$+*5)'%!5)!$*('+)#+!-.+!/+7%#(!5),+*&)!')$)!5)!(*4(#+!Y$+*!+&+4$)(3!
(*4(#)!')*()5+)Z3!(/)7(+/+4+#')3!,)'%4)#+3!+",/"-'9))
Glomerulonefriti primitive
H(&&)6)/)!-%1&+!5)!&)#5*(4+!#+0*(&)-%G!

! bambini < 60 anni > 60 anni

!
MCD 76% 20% 20%
GSF 8% 15% 2%
GN membranosa 7% 40% 39%
MPGN 4% 7% --
altre 5% 18% 39%
Nefropatia diabetica
Amiloidosi renale
Cause rare
glomerulopatia fibrillare malattia da deposito di catene leggere
pre-eclampsia forme post-infettive e para-infettive
neoplasie (in genere MCD) malattie sistemiche (LES, altre
collagenopatie, vasculiti)
GN eredofamiliari (sindrome di Alport, nail-patella sindrome)
Reazioni allergiche (farmaci, veleni, punture di insetti, antigeni inalati)
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5)!0)/'*%2)(#+!7/(4+*1/%*+!Yhk^Z!5+/!ISR!(!5+//%!5)1*+&)!%!4+#(!5)!P3S!4/U]7!$+*!
$%#,()Z)$,([)
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%#1*)%!$+*!WI!(*+C!
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'*+!4+&)8)!
)
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!
A modification of the RIFLE criteria has been proposed by the Acute Kidney Injury
`+-+#'+4+#'+!?!&'%'%!$*($(&'%!1#%!#1(,%!-/%&&)0)-%2)(#+!6%&%'%!)#!$%*'+!&1)!-*)'+*)!
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Network. The AKIN proposed both diagnostic criteria for ARF and a staging
4%#+77+,(/+!&1/!$)%#(!-/)#)-(8!"!-*)'+*)!Mn"b!$*($(#7(#(3!)#(/'*+3!5)!%5(''%*+!/%!
system that was based on the RIFLE criteria. In addition, the term acute kidney
5+0)#)2)(#+!$)F!7+#+*)-%!5)!@M-1'+!])5#+o!)#p1*oA8!
injury (AKI) was proposed to represent the entire spectrum of acute renal failure.
!

* Modified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria. The staging system
b+//%!$*%')-%!-/)#)-%!)!-*)'+*)!Mn"b!&+46*%#(!)#!+00+'')!$)F!0%-)/4+#'+!%''1%6)/)8!
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*+#%/+!+!-(#!&-(4$+#&(!-%*5)%-(8!"!kMbO3!)#,+-+3!%7)&-(#(!)#)6+#5(!/%!&)#'+&)!5)!
$*(&'%7/%#5)#+!,%&(5)/%'%'*)-)!)#!&+5+!*+#%/+3!+!:1+&'(!$1N!5+'+*4)#%*+!)#!$%*')-(/%*)!
-(#5)2)(#)!1#(!&'%'(!5)!#+-*(&)!)&-.+4)-%!%!/),+//(!'161/%*+8!!
EB"`M!5%!-%1&+!$*+<*+#%/)!?!)#)2)%/4+#'+!1#B)#&100)-)+#2%!*+#%/+!+1*2'$*"%(G!&+3!$+*N3!
#(#!,)+#+!*)4(&&%!+00)-%-+4+#'+!+!*%$)5%4+#'+!/%!-%1&%!&-%'+#%#'+3!)/!5%##(!01#2)(#%/+!
5+'+*4)#%!%#-.+!/%!#+-*(&)!'161/%*+!&1!6%&+!)&-.+4)-%3!+!%!:1+&'(!$1#'(!&)!)#&'%1*%!
%#-.+!1#%!-(4$(#+#'+!$,&"*'-"),(*"%(3!-)(?!/%!#+-*(&)!'161/%*+!%-1'%8!!
Ipoperfusione renale

Ischemia dei nefroni corticali superficiali e riduzione del GFR

Innesco di meccanismi di compenso del GFR

efficacia del compenso

SI NO

recupero viraggio verso


funzionale il danno organico
ischemico

!
Diagnosi differenziale della Insufficienza Renale Acuta

pre-renale renale
(funzionale)! (organica ischemica)!

Osmolarit urinaria sensibilit del rene


(mOsm/L)! > 500 < 350
allADH
sensibilit del rene
Frazione di escrezione <1 > 1 (>2 NTA)!
del sodio
al feedback
glomerulo-tubulare
sodiuria (mEq/die)! < 20 idem > 40

azotemia/creatininemia > 20 idem < 10

risposta diuretica al sensibilit renale agli


SI NO
mannitolo stimoli diuretici osmotici
!
!
!
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%66%&'%#2%!*%*+!5)!"`M8!
< ;"10()7"0-$%",'Q)#+//+!,%&-1/)')!+!#+//B)$+*'+#&)(#+!4%/)7#%!/B%/'+*%2)(#+!5+//%!
$+*,)+'>!5+//+!%*'+*)(/+!5+/!$%*+#-.)4%!*+#%/+!$1N!$(*'%*+!%//B"`M8!
< `%$/(,1%$*(+,'#()"-1#"!
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#$00'-.(9!"!'(&&)-)3!%!/(*(!,(/'%3!&)!5)&')#71(#(!)#!+&(7+#)!+5!+#5(7+#)8!"!'(&&)-)!
+&(7+#)!&(#(!&($*%''1''(!7/)!%#')6)(')-)!#+0*('(&&)-)!Y+&G!%4)#(7/1-(&)5)Z3!"!
-.+4)('+*%$)-)!Y-)&$/%')#(Z!+!"!4+22)!5)!-(#'*%&'(8!"!'(&&)-)!+#5(7+#)!&(#(3!$+*!
+&+4$)(G!/'$&%$C'*"3!)#!-(*&(!5)!4)(7/(6)#1*)%!-%1&%'%!5%!*%65(4)(/)&)!
4%&&),%C!(/$&%$C'*"3!)#!-(*&(!5)!%#+4)+!+4(/)')-.+!%-1'+!5)!#('+,(/+!+#')'>!-.+!
-%1&%#(!+4(7/(6)#1*)%!:1%#5(!,)+#+!&%'1*%'%!/B%$'(7/(6)#%C!6,$#('*()
'*#,"#1C1%",'G)-(4+!%--%5+!#+/!4)+/(4%!41/')$/(!-(#!/%!$*('+)#1*)%!5)!q+#-+<
r(#+&!Y*+#+!5%!4)+/(4%Z8!
Cause pi frequenti:
Calcolosi urinaria
Neoplasie delle vie urinarie o extraurinarie (specie della pelvi)!
Ipertrofia prostatica
! Fibrosi retroperitoneale
Emorragie retroperitoneali
!
Legatura accidentale degli ureteri
\%1&+!$(&'<*+#%/)!
Stenosi cicatriziali da flogosi croniche della pelvi
! Presenza di coaguli nelle vie urinarie
O(&'%#2)%/4+#'+3!&(#(!'1''+!/+!-%1&+!5)!(--/1&)(#+!5+//+!,)+!1*)#%*)+8!O)!'*%''%!5)!&'1%2)(#)!
Stenosi delluretra (valvole congenite, stenosi cicatriziali, fimosi)!
(*4%)!$)1''(&'(!*%*+8!
La ostruzione urinaria favorisce linfezione urinaria e la calcolosi e pertanto va
rapidamente risolta o rimuovendo, se rimovibile , lostacolo al deflusso urinario,
oppure deviando allesterno le urine (sonde nefrostomiche o stent endoluminali).

La risoluzione della ostruzione provoca rapida ripresa della funzione renale, eccetto
che nel caso in cui la ostruzione sia stata molto protratta ed abbia provocato danni
irreversibili al parenchma renale (danno ischemico da compressione operato dalla
sovradistensione della pelvi e dei bacinetti)!
!
)
O)#'(4)!
!
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!
1) Contrazione della diuresi (o diuresi conservata)!

2) Ritenzione cataboliti azotati


(innalzamento della azotemia, della creatininemia, della uricemia,
encefalopatia, altosi, nausea, vomito, cefalea, pericardite uremica)!

3) Ritenzione idrica (se persistente contrazione della diuresi)!


(edema, versamenti cavit sierose ,ipertensione arteriosa, sovraccarico
cardiaco sino alledema polmonare acuto, aritmie)!
4) Ritenzione salina
(iperpotassiemia, iperfosforemia con conseguente ipocalcemia)!

5) Ritenzione acidi organici (fosfati e solfati)!


(acidosi metabolica con polipnea compensatoria )!
!
!
6) Anemia e pallore della cute e delle mucose visibili

7) Suscettibilit alle infezioni

8) Suscettibilit alle emorragie

9) Segni e sintomi riferibili alla causa di insufficienza renale


esposizione recente a farmaci o tossici
episodi recenti di possibile protratta ipoperfusione renale
segni di rabdomiolisi, di emolisi, di colestasi grave
ipocomplementemia, ematuria, sedimento attivo
manovre endovascolari recenti
segni di microangiopatia trombotica
artralgie, porpora, positivit agli ANCA o altri autoanticorpi
eosinofilia ematica
!
!
!
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!

Si osserva generalmente dopo circa 20 giorni dallesordio della insufficienza


renale acuta.

Sono fattori che si oppongono alla rigenerazione epiteliale:


pre-esistente insufficienza renale cronica (IRA sovrapposta ad IRC)!
intensa vasocostrizione corticale
danno esteso della membrana basale tubulare (tubuloressi)!
liberazione di enzimi litici e di radicali dellossigeno da parte di leucociti
migrati dal circolo ematico, che affluiscono attorno ai tubuli danneggiati
liberazione di enzimi proteasici (es. caspasi) da parte di cellule epiteliali
danneggiate
distacco di cellule necrotiche epiteliali dalla membrana basale tubulare,
con ostruzione del lume tubulare, aumento della pressione
endoluminale e retrofiltrazione di preurina nellinterstizio
!
!
!

!
!
!
!

!
!
!

!
!
!
!

!
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Ipertensione glomerulare
Nel diabetico si verifica, fin dallinizio della malattia, prima che insorga la
microalbuminuria, un aumento del GFR. Il fenomeno, che si associa ad
ipertrofia dei glomeruli ed aumento del volume dei reni, pi evidente nel
diabete tipo 1.

Leccesso di glucosio filtrato a causa delliperglicemia viene riassorbito nel


tubulo prossimale dal sistema di cotrasporto sodio-glucosio. Questo
fenomeno ha due conseguenze
1) Laccumulo di sodio e quindi di acqua espande la volemia e provoca la
stimolazione dei recettori di stiramento atriale e quindi la secrezione
cardiaca del peptide natriuretico atriale (ANP) che essendo un potente
vasodilatatore provoca la vasodilatazione dellarteriola afferente e quindi
laumento della pressione glomerulare e del GFR
2) La ridotta quantit di sodio che raggiunge la macula densa in conseguenza
delleccessivo riassorbimento prossimale modifica il feedback tubulo-
glomerulare, attivando meccanismi che portano alla vasodilatazione
dellarteriola afferente ed alla vasocostrizione dellarteriola efferente.

Lipertensione glomerulare fra i principali determinanti del danno a


carico della membrana basale glomerulare e quindi dellinsorgenza
della nefropatia diabetica

!
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Controllo glicemico !

Il controllo intensivo della glicemia, se realizzato


prima dellinsorgenza di danni terminali irrever-
sibili a carico degli organi bersaglio, riduce
lincidenza delle complicanze macro- e micro-
angiopatiche del diabetico.
Dal punto di vista renale, questo approccio si
dimostrato valido in tutti i pazienti ad eccezione di
quelli con proteinuria conclamata, in cui il controllo
rigoroso della pressione con un bloccante del
sistema renina-angiotensina sembra essere pi
importante.

!
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#1##')')*(+,$*'9)"!#+0*(#)3!$(-(!%!$(-(3!,%##(!)#-(#'*(!%//%!6(,3'#")3(')6$3$-'#'!D!:1+&'(!
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&)#5*(4+!#+0*(&)-%!Y*%*(Z8!!

!
Alterazioni morfologiche
O'%5)!5+//%!#+0*($%')%!5)%6+')-%!

1. Aumento di volume dei reni per ipertrofia dei


tubuli, aumento della componente interstiziale,
aumento del volume dei glomeruli per aumento
della lunghezza e del diametro dei capillari
2. Ispessimento della membrana basale glomerulare
e tubulare
3. Espansione mesangiale
a) diffusa
b) nodulare (Kimmelstiel Wilson)
4. Sclerosi (obsolescenza) glomerulare
5. Ialinosi dellarteriola afferente ed efferente
6. Depositi lineari di IgG nella MBG
7. Degenerazione atrofia tubulare e fibrosi
interstiziale !

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/(-%/)22%'(!%!/),+//(!5+/!$(/(!1*)#%*)(!5+//%!-%$&1/%!5)!q(f4%##!D!-.+!$1N!5%*+!(*)7)#+!%!
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'+4$(!5+-)&%4+#'+!/1#7.)8!L1)#5)3!)/!$%2)+#'+!-(#!5%##(!7/(4+*1/%*+!$1N!+!5+,+!+&&+*+!
'*%''%'(!-(#!/B(6)+''),(!5)!+",),(&,(3',()'%)3"**$!5%#5(!)/!'+4$(!%/!7/(4+*1/(!5)!
*)$%*%*&)!%#-.+!#+//%!&1%!-(4$(#+#'+!$(5(-)'%*)%8!977)!&%$$)%4(!-.+!:1+&'(!?!1#!
(6)+''),(!-.+!$(&&)%4(!*%7)(#+,(/4+#'+!$(*-)3!4%!-.+!$1*'*($$(!#(#!?!&+4$*+!
Primitive
*%77)1#7)6)/+8! Secondarie

\/%&&)0)-%2)(#+!
Nefropatia ad IgA Malattie sistemiche a patogenesi autoimmune
GN membranosa nefrite lupica
E+!$%'(/(7)+!7/(4+*1/%*)!$(&&(#(!+&&+*+!5)!')$(!'*+'"//"#$,'$)Y&%$/(,1%$*(+,'#'Z!
Glomerulosclerosi focale e segmentale vasculiti
($$1*+!$(&&(#(!+&&+*+!5)!')$(!#(#!$*($*)%4+#'+!)#0)%44%'(*)(!Y&%$/(,1%$6"#'(3!
GN Proliferativa mesangiale Disgammaglobulinemie
$*)-)%$%/4+#'+!/%!7/(4+*1/($%')%!5)%6+')-%!+!/+!7/(4+*1/($%')+!5%!5+$(&)2)(#+!5)!
GN Post-infettive Amiloidosi renale
$%*%$*('+)#+Z8!"#!*+%/'>3!$+*N3!4(/'+!7/(4+*1/(#+0*)')!&(#(!$%'(/(7)+!#+//+!:1%/)!#(#!
GN Membranoproliferativa
Crioglobulinemia mista essenziale
+&)&'+!1#%!,+*%!+!$*($*)%!-%1&%!)441#(/(7)-%G!:1+&'%!5)&')#2)(#+3!%#-.+!&+!1')/+!5%/!
Nefropatia ad IgM
Mieloma
$1#'(!5)!,)&'%!5)5%'')-(3!?!:1)#5)!$(-(!,+*)')+*%8!!
Malattia a lesioni minime
GN a semilune
\/%&&)-%4+#'+3!/+!4%/%'')+!7/(4+*1/%*)!
Ereditarie &(#(!&'%'+!5)&')#'+!)#!6,'/'#'7()+!
0(-$*3",'(G!&+-(#5%*)+!&(#(!/+!0(*4+!
Sindrome di Alport
Malattia di Anderson-Fabry
-.+!-(4$%)(#(!#+/!-(#'+&'(!5)!1#%!
Malattia a membrane sottili $%'(/(7)%!&)&'+4)-%3!4+#'*+!:1+//+!
Deficit di Lecitina-Colesterolo acil-transferasi $*)4)'),+!&(#(!)#!7*%#!$%*'+!)5)($%')-.+8!!
Glomerulopatia da lipoproteine
Cistinosi a&)&'(#(!$()!1#%!&+*)+!5)!4%/%'')+!
Sindrome nefrosica finlandese 7/(4+*1/%*)!(,(3'#",'(3!*%*+8!T#!'+4$(!
Sclerosi mesangiale diffusa
:1+&'+!$%'(/(7)+!-%1&%,%#(!/%!4(*'+!5+/!$%2)+#'+!)#!7)(,%#)&&)4%!+'>G!(77)!-.+!&)%4(!)#!

Glomerulonefrite
7*%5(!5)!0%*!&($*%,,),+*+!:1+&')!6%46)#)!0)#(!%//B+'>!%51/'%3!-(#(&-)%4(!4(/'(!4+7/)(!/(!
&$+''*(!5+//+!-(4$/)-%')&&)4+!%#(4%/)+!7+#+')-.+!-.+!$(&&(#(!-%1&%*+!$%'(/(7)+!*+#%/)!
$*)4)'),+8!

Primitive Secondarie
V*%!/+!7/(4+*1/(#+0*)')!$*)4)'),+3!/%!
#+0*($%')%!%5!"7M!?!&)-1*%4+#'+!/%!$)F!
0*+:1+#'+3!)#'+*+&&%#5(!$*(6%6)/4+#'+!
Nefropatia ad IgA /BWR!5+//%!$($(/%2)(#+3!&($*%''1''(!#+//+!
Malattie sistemiche a patogenesi autoimmune
GN membranosa $($(/%2)(#)!%&)%')-.+3!5(,+!.%!
nefrite lupica
Glomerulosclerosi focale e segmentale 1#B)#-)5+#2%!5%,,+*(!+/+,%'%8!d!1#%!
vasculiti
GN Proliferativa mesangiale $%'(/(7)%!-.+!$(*'%!-(#!&[!%/'+*%2)(#)!
Disgammaglobulinemie
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GN Post-infettive Amiloidosi renale
4)-*(+4%'1*)%3!+!)!$%2)+#')!&(#(!
GN Membranoproliferativa
Crioglobulinemia mista essenziale
%&&(/1'%4+#'+!%&)#'(4%')-)3!$+*'%#'(!
Nefropatia ad IgM #(#!,+#),%!5%'%!)4$(*'%#2%!%!'%/)!
Mieloma
Malattia a lesioni minime *)&-(#'*)8!d!')$)-%4+#'+!1#%!$%'(/(7)%!
GN a semilune 5+/!7)(,%#+8!!

omerulonefrite
!
Ereditarie

Sindrome di Alport !
Secondarie
Malattia di Anderson-Fabry
Malattia a membrane sottili V*%!/+!7/(4+*1/(#+0*)')!&+-(#5%*)+!/%!$)F!
MalattieD eficit dia Lecitina-Colesterolo
sistemiche patogenesi autoimmune acil-transferasi
)4$(*'%#'+!?!&)-1*%4+#'+!/%!#+0*)'+!/1$)-%3!
Gnefrite
lomerulopatia
lupica da lipoproteine &+71)'%!5%//+!%/'*+!,%&-1/)')!%1'()441#)8!h)!&(#(!
segmentale Cvasculiti
istinosi $()!/+!,%*)+!5)&7%44%7/(61/)#+4)+8!
e Sindrome nefrosica finlandese
Disgammaglobulinemie
SAmiloidosi
clerosi mesangiale
renale diffusa !
Crioglobulinemia mista essenziale
Le !
cause principali di glomerulonefrite sono
Mieloma
! diverse in differenti gruppi det

La frequenza delle glomerulonefriti Lincidenza annuale delle


nellanziano rispetto alladulto di glomerulonefriti tra i bambini
30.8 vs. 28.3 casi per milione. italiani di 11.1 casi per milione.
y
Le forme pi frequenti sono le Le forme pi frequenti sono le seguenti:
i
seguenti:
rolo acil-transferasi
ine Nefropatia ad IgA (18.8%)
GN Membranosa (13.4 vs.4.2 PMP)
ese Malattia a lesioni minime (11.6%),
GN a semilune (3.1 vs.0.9 PMP)
Glomerulosclerosi focale e
GN Membranoproliferativa (2.9 vs. segmentale (8.5%),
0.4 PMP) GN proliferativa mesangiale
(9.5%),
GN acuta post-streptococcica (0.9
vs. 0.4 PMP) GN Membranoproliferativa
(5.5%),
Nefrite lupica (5%)
!
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1#%!7/(4+*1/(#+0*)'+!:1%#5(!*)&-(#'*)%4(!%/'+*%2)(#)!5+/!&+5)4+#'(3!+!5(66)%4(!&16)'(!
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5)!7/(4+*1/(#+0*)'+3!4%!#(*4%/4+#'+!#(#!&(#(!$*+&+#')8!V)$)-%4+#'+!)!$%2)+#')!.%##(!
&+4$/)-+4+#'+!+4%'1*)%!4)-*(&-($)-%!+!$*('+)#1*)%8!E+!4%#)0+&'%2)(#)!-/)#)-.+3!:1)#5)3!
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Sindromi cliniche associate alle
principali forme di glomerulonefrite
Sindrome Sindrome Anomalie Ematuria
nefrosica nefritica urinarie isolata
Malattia a lesioni minime +++++ - ++ -/+

GN membranosa ++++ + ++ -/+

GS focale e segmentale +++ + ++ -/+

Nefropatia ad IgA ++ +++ ++++ ++++

GN membranoproliferativa +++ +++ ++++ -/+

GN proliferativa endocapillare + ++++ ++++ ++

GN a semilune + ++++ ++++ -


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< H%2)+#')!(6+&)!
< \(%71/($%')+!
< k1#2)(#+!*+#%/+!5+'+*)(*%'%!
< `+#+!$)--(/(!Y$+*-.[!)#5)-%'),(!5)!$%'(/(7)%!-*(#)-%!)**+,+*&)6)/+Z!
< V14(*)!*+#%/)!Y*)&-.)(!5)!)#&++5)#7Z!
< H%2)+#')!#(#!5)&$(&')!%!-(($+*%*+!
< "#0+2)(#)!*+#%/)!(!$+*)*+#%/)!
< h%&-1/)')!-(#!41/')$/)!%#+1*)&4)!)#'*%*+#%/)!

>9 `%$/(,1%$*(+,'#')*$*)6,$%'+(,"#'7()
< `%$/(,1%$*(+,'#()/(/C,"*$0")
< `%$/(,1%$*(+,'#()")%(0'$*')/'*'/()
Glomerulonefrite membranosa
< `%$/(,1%$0-%(,$0')+$-"%()0(&/(*#"%()

`%$/(,1%$*(+,'#()/(/C,"*$0")
La glomerulonefrite membranosa una malattia immunologica
anticorpo-mediata nella quale gli immunocomplessi si localizzano sul
a&(*5)&-+!:1%&)!&+4$*+!-(4+!1#%!&)#5*(4+!#+0*(&)-%3!(!-(41#:1+!-%1&%!1#%!
versante sottoepiteliale del capillare glomerulare, tra la membrana
$*('+)#1*)%!7*%,+8!H1N!+&&+*+!$*+&+#'+!+4%'1*)%3!4%!4%)!5)!7*%5(!)4$(*'%#'+G!
basale ed il podocita.
1#B+4%'1*)%!&+*)%!-)!-(#&+#'+!7)>!5)!+&-/15+*+!/%!^b!4+46*%#(&%8!!

Anticorpi si legano in situ ad


E%!^b!4+46*%#(&%!?!1#%!$%'(/(7)%!
)441#(4+5)%'%!5(,1'%!%//%!3(6$0'2'$*()3')
antigeni esogeni cationici ed a
'//1*$-$/6%(00'!#+//%!4%'*)-+!
basso peso molecolare
+g'*%-+//1/%*+!5+//%!4+46*%#%!5)!0)/'*%2)(#+G!
previamente depositatisi sulla
:1+&'(!?!-)N!-.+!,+5)%4(!%//%!6)($&)%!*+#%/+3!
parete esterna della MBG
5+$(&)')!5)!4%'+*)%/+!$*('+)-(!+(&)#(0)/(!%/!5)!
Immunocomplessi formatisi in
rulonefrite membranosa
&(''(!5+)!$(5(-)')8!
circolo attraversano la MBG
depositandosi sulla sua parete
H*(6%6)/4+#'+3!&)!'*%''%!5)!1#%!$%'(/(7)%!
esterna.
:1%&)!&+4$*+!&+-(#5%*)%G!!
efrite membranosa una malattia immunologica
Autoanticorpi si legano in situ a
iata nella quale gli immunocomplessi si localizzano sul < 45)1*")0'*3,$/()6","*($6%"0#'-")
oepiteliale del capillare glomerulare, tra la membrana una componente costitutiva
V)$)-%4+#'+!)#!-(*&(!5)!'14(*)!&(/)5)!
docita. delle cellule epiteliali della
Y-(/(#<*+''(3!$(/4(#+Z!)#!$%2)+#')!
parete capillare (es, la megalina)!
Anticorpi si legano in situ ad %#2)%#)8!
antigeni esogeni cationici ed a < O"%"##'()"1#$'//1*')
basso peso molecolare E%!#+0*)'+!4+46*%#(&%!?!/%!-/%&&+!h!
previamente depositatisi sulla 5+//%!#+0*)'+!/1$)-%8!
parete esterna della MBG < R*+(2'$*')
Immunocomplessi formatisi in O($*%''1''(!+$%')'+!q3!&)0)/)5+3!
circolo attraversano la MBG 4%/%*)%!5%!H8!4%/%*)%+8!!
depositandosi sulla sua parete < ^",/"-')
esterna. H+#)-)//%4)#%3!&%/)!5B(*(3!-"6#$6,'%G)
Autoanticorpi si legano in situ a ^S=<3!-.+!$*(6%6)/4+#'+!&(#(!1#%!
una componente costitutiva 5+//+!-%1&+!$*)#-)$%/)!5)!^b!
delle cellule epiteliali della 4+46*%#(&%!Y7*(&&+!5(&)!$+*!'+4$)!
parete capillare (es, la megalina)! $*(/1#7%')3!/%!$%'(/(7)%!*+-+5+!-(#!
/%!&(&$+#&)(#+!5+//B1&(Z8!!
O)!?!,)&'(3!-(#!:1+&')!-*)'+*)3!-.+!-)*-%!)/!WSR!5+//+!^b!4+46*%#(&+!&(#(!
,+*(&)4)/4+#'+!-%1&%'+!5%)!kMbO8!!
a&)&'(#(!$()!:1+//+!+')-.+''%'+!-(4+!'3'$6"#'-.(3!%#-.+!&+!D!$*(6%6)/4+#'+!D!
#(#!+&)&'(#(!0(*4+!*+%/4+#'+!)5)($%')-.+8!
Istologicamente si ha un ispessimento omogeneo e diffuso
!
della membrana basale. A seconda del grado di ispessimento
"&'(/(7)%! si distinguono 4 stadi.
!
!
!
!
!

!
Nel primo stadio anche a maggior Tuttavia, pur in assenza di evidenti
ingrandimento le pareti capillari depositi al microscopio ottico, !
non presentano evidenti aspetti di l'immuno-fluorescenza
ispessimento o evidenti depositi caratterizzata da depositi
sottoepiteliali. fluorescenti diffusi lungo la
membrana basale, con aspetto
finemente granulare o simil-
lineare.
!

La colorazione argentica mette in Nel III stadio a forte ingrandimento


risalto piccole estroflessioni nere evidente il massivo
(spikes) si proiettano all'esterno ispessimento delle pareti capillari,
della membrana basale assumendo con la tendenza della membrana
il tipico aspetto di "denti di pettine". basale ad estendersi e ricoprire i
Queste spicule sono separate dai depositi facendoli apparire
depositi sottoepiteliali che non si incapsulati ed inglobati.
colorano all'argento e caratterizzano
il II stadio. !
O1//%!6%&+!5+//B)&'(/(7)%!+!5+//B)&$+&&)4+#'(!5+//%!4+46*%#%!6%&%/+3!&)!5)&')#71(#(!
:1%''*(!&'%5)!$*(7*+&&),)8!

_+-(*&(!

L)g*)#(,2$)3(')6"2'(*#')7")'*-$*#,$)"),(/'00'$*()06$*#"*(")#+/!7)*(!5)!1#!%##(U1#!
%##(!+!4+22(C!:1+&'%!?!1#%!$*(,%!5+//%!&+-(#5%*)+'>!5+//%!4%/%'')%G!*)4(&&(!/(!&')4(/(!D!
%#-.+!)#%,,+*')'%4+#'+!D!&+!#+!,%!%#-.+!/%!4%/%'')%8!

L)g*)#(,2$)3(')6"2'(*#')07'%166")1*)a1"3,$)-,$*'-$)3')*(+,$0')-.()*$*)6,$&,(3'0-()
7(,0$)%5'*01++'-'(*2"),(*"%()#(,/'*"%(9)

L)g*)#(,2$)3(')6"2'(*#')7")'*-$*#,$)"3)'*01++'-'(*2"),(*"%()#(,/'*"%(9)

O)--(4+!1#!'+*2(!5+)!$%2)+#')!,%!)#!*+4)&&)(#+!&$(#'%#+%3!&)!'+#5+!%!#(#!'*%''%*+!&16)'(!
/%!4%/%'')%3!$*($*)(!#+//B+,+#'1%/)'>!-.+!&)!'*%'')!5)!1#%!0(*4%!&+-(#5%*)%!/%!-1)!(*)7)#+!
&)%!5%!*)-+*-%*+8!L1+//(!-.+!#(#!4%#-%3!$+*N3!?!/%!'+*%$)%!-(#!M\a<"!+!&%*'%#)3!4)*%'%!%!
*)51**+!/%!$*('+)#1*)%8!O+!+#'*(!51+!%##)!#(#!&)!('')+#+!*+4)&&)(#+!Y(!)#!-%&(!5)!0(*4+!
%77*+&&),+Z!&)!$1N!$+#&%*+!5)!'*%''%*+!)/!$%2)+#'+!-(#!&'+*()5)!+5!)441#(&($$*+&&(*)C!
(77)!&)!1')/)22%!4(/'(!)/!*)'1g)4%6!YX%6V.+*%Z3!%#')-(*$(!4(#(-/(#%/+!%#')<\_IP!-.+!&)!
&'%!*),+/%#5(!$)1''(&'(!+00)-%-+8!

O"%"##'")")%(0'$*')/'*'/()

M#-.+!:1+&'(!?!1#!:1%5*(!#(#!$*(/)0+*%'),(3!+!&)!,+5+!#+)!6%46)#)G!$1N!+&&+*+!%&&(-)%'%!
%!/+1-+4)+!+!/)#0(4)!+!&)!$*+&+#'%!-(#!4%77)(*+!0*+:1+#2%!#+7/)!%'($)-)!)4$(*'%#')8!
V)$)-%4+#'+3!)/!6%46)#(!&)!$*+&+#'%!7(#0)(3!+5+4%'(&(!+!,)+#+!*)-(,+*%'(8!_1*%#'+!
:1+&'(!$*)4(!+$)&(5)(!#+0*(&)-(!%-1'(3!&$+&&(!,)+#+!)4$)+7%'%!1#%!'+*%$)%!+g!)1,%#')61&!
-(#!1#(!&'+*()5+3!5($(5)-.[!)/!6%46)#(!,%!)#!*+4)&&)(#+8!H1*'*($$(3!$+*N3!&(/(!)/!IPR!
5+)!6%46)#)!71%*)&-+G!)!*+&'%#')!%,*%##(!*+-)5),+8!M/-1#)!$%2)+#')3!5($(!1#!-+*'(!#14+*(!
5)!*+-)5),+!D!&$+&&(!&-%'+#%'+!5%!+$)&(5)!)#0+''),)!<3!%#5*>!5+0)#)'),%4+#'+!)#!*+4)&&)(#+8!
97#)!*+-)5),%!$1N!+&&+*+!'*%''%'%!+00)-%-+4+#'+!-(#!7/1-(-(*')-()5)3!5%!:1)!/B)5+%!
'*%5)2)(#%/+!-.+!:1+&'%!0(*4%!5)!^b!&)%!&1!6%&+!)441#(/(7)-%8!\.)%*%4+#'+3!5($(!1#!
$+*)(5(!5)!-%*)-(!+!5)!4%#'+#)4+#'(3!&)!'+#'%!5)!*)51**+!)/!5(&%77)(!0)#(!%//%!&(&$+#&)(#+8!
X(/')!6%46)#)3!%//%!&(&$+#&)(#+!5+//(!&'+*()5+3!*)4%#7(#(!/)6+*)!5%!$*('+)#1*)%!+!
,),*%##(!6+#)&&)4(!0)#(!%5!1#%!+,+#'1%/+!&1--+&&),%!*+-)5),%!D!-(4+!&)!5)-+,%3!:1%&)!
&+4$*+!&-%'+#%'%!5%!)#0+2)(#)8!T#!-+*'(!#14+*(!5)!6%46)#)3!$+*N3!5),+#'%!&'+*()5(<
5)$+#5+#'+8!"#!:1+&'(!-%&(3!$+*!+,)'%*+!5)!+--+5+*+!-(#!/(!&'+*()5+!)#!1#!(*7%#)&4(!)#!
-*+&-)'%3!&)!1')/)22%#(!7/)!)441#(&($$*+&&(*)!-(4+!&'+*()5<&$%*)#7!%7+#'&8!a&)&'(#(!$()!)!
$%2)+#')!0#(,$'3$L,(0'0#(*#'G!7+#+*%/4+#'+!/%!&'+*()5(<*+&)&'+#2%!&)!4%#)0+&'%!%5!)#)2)(!
'+*%$)%3!4%!+&)&'(#(!%#-.+!-%&)!5)!&'+*()5(<*+&)&'+#2%!%-:1)&)'%!)#!-(*&(!5)!'+*%$)%8!"#!
:1+&')!-%&)3!)/!SPR!5+)!6%46)#)!&(#(!)#!*+%/'>!%00+''!5%!1#%!6"#$%$&'")&(*(#'-"!-.+!
-(/$)&-+!)/!*+#+8!k)#(*%!#+!&(#(!&'%'+!)5+#')0)-%'+!WI3!+5!?!$(&&)6)/+!-.+!%#-.+!)/!*+&'%#'+!
SPR!5)!$%2)+#')!&'+*()5(<*+&)&'+#')!$(&&%#(!+&&+*+3!)#!01'1*(3!)#-/1&)!)#!:1+&'(!7*1$$(8!"/!
'*)77+*3!%#-.+!$+*!)!$%2)+#')!-(#!4%/%'')%!7+#+')-%3!&+46*%!-(41#:1+!+&&+*+!
1#B)#0+2)(#+3!(!-(41#:1+!1#%!#(g%!$%'(7+#%!-.+3!#+/!6%46)#(!-(#!-)'(&-.+/+'*(!
$(5(-)'%*)(!7+#+')-%4+#'+!5+0)-)'%*)(3!?!)#!7*%5(!5)!5+'+*4)#%*+!/B)#)2)(!5+/!5%##(8!!

L1%#5(!)/!6%46)#(!&,)/1$$%!
&'+*()5(<5)$+#5+#2%!(!&'+*()5(<
Per definizione nella *+&)&'+#2%!5($(!1#!-)-/(!5)!Q!
glomerulonefrite a lesioni minime i 4+&)3!'*%5)2)(#%/4+#'+!&)!?!
glomeruli appaiono sostanzialmente
normali &+4$*+!0%''%!/%!6)($&)%!*+#%/+8!
M//%!6)($&)%3!%//+!,(/'+!&)!
*)&-(#'*%,%!1#!:1%5*(!%!/+&)(#)!
4)#)4+3!4%!&($*%''1''(!#+)!
$%2)+#')!*+&)&'+#')!&)!*+$+*'%,%!
)#,+-+!-(#!1#%!-+*'%!0*+:1+#2%!
Al ME, la membrana basale ha
un decorso tortuoso e si
1#(!&'%'(!5)!7/(4+*1/(&-/+*(&)!
apprezza la "fusione" completa 0(-%/+!&+74+#'%*)%8!
dei pedicelli.

E%!^b!4+46*%#(&%!+!/%!
7/(4+*1/(&-/+*(&)!0(-%/+!
&+74+#'%*)%3!$*)4%!*)'+#1'+!$%'(/(7)+!#+''%4+#'+!5)&')#'+3!&+46*%#(!(77)!+&&+*+!51+!
+#')'>!&'*+''%4+#'+!1#)'+3!+!)/!*)&-(#'*(!5+//B1#%!(!5+//B%/'*%!)#!1#!5%'(!$%2)+#'+!
5)$+#5+*+66+!+&&+#2)%/4+#'+!5%/!4(4+#'(!)#!-1)!&)!,%!%!0%*+!/%!6)($&)%3!+!/%!
7/(4+*1/(&-/+*(&)!0(-%/+!&+74+#'%/+!*%$$*+&+#'+*+66+!1#%!0%&+!5)!5%##(!$)F!%,%#2%'%8!
L1)3!,(/+#5(3!&)!*)'(*#%!%/!5)&-(*&(!)#)2)%/+!&1//B)4$(*'%#2%!5+//%!:1('%!*+&)51%!5)!
$(5(-)')8!!

b+)!$%2)+#')!&'+*()5(<*+&)&'+#')!&)!1')/)22%#(!)#!7+#+*+!-)-/(&$(*)#%3!*)'1g)4%6!(!
-)-/(0(&0%4)5+3!-(#!'1'')!)!$*(6/+4)!5)!7*%,+!'(&&)-)'>!)44%7)#%6)/)8!H1*'*($$(3!$+*N3!&(/(!
1#%!$)--(/%!$%*'+!5)!:1+&')!$%2)+#')!('')+#+!/%!*+4)&&)(#+!-(#!/B)441#(&($$*+&&(*+G!
5B%/'*%!$%*'+3!-(4+!&)!5)-+,%3!:1+&')!&(#(!#+//%!4%77)(*!$%*'+!5+)!-%&)!:1%5*)!7+#+')-)!
4)&-(#(&-)1')8!L1)#5)3!/%!7+&')(#+!5)!:1+&')!$%2)+#')!?!5)00)-)/+!+!$*)#-)$%/4+#'+!
0)#%/)22%'%!%//%!/)4)'%2)(#+!5+//%!$*('+)#1*)%3!(6)+''),(!-.+!&)!$1N!*%77)1#7+*+!D!%!,(/'+!
%#-.+!)#!4(5(!4(/'(!&(55)&0%-+#'+!D!-(#!7/)!M\a<"!+5!)!&%*'%#)8!

"#!%/-1#)!-%&)3!/%!4%/%'')%!%!/+&)(#)!4)#)4+!?!-(#7+#)'%!+!&)!$*+&+#'%!:1)#5)!7)>!%//%!
#%&-)'%G!)#!:1+&')!-%&)!)!6%46)#)!$(&&(#(!*)&1/'%*+!$(&)'),)!%//(!&-*++#)#7!$+*!
/B)$(')*()5)&4(!-(#7+#)'(!$()-.[3!%!-%1&%!5+//%!$*('+)#1*)%3!$+*5(#(!/%!Vq^8!!

_+-(*&(!
E%!4%/%'')%!.%!#+//%!4%77)(*!$%*'+!5+)!-%&)!5+-(*&(!6+#)7#(!+!$1N!+&&+*+!-(#'*(//%'%!
-(4$/+'%4+#'+!-(#!7/)!&'+*()5)8!EB)5+%!-.+!&)%!1#%!$%'(/(7)%!&1!6%&+!)441#(/(7)-%!
-(#'*%&'%!-(#!/B%&&+#2%!5+/!*)&-(#'*(!5)!)441#(-(4$/+&&)!%/!/),+//(!*+#%/+G!
$*(6%6)/4+#'+!&)%4(!5)!0*(#'+!%!'%#'+!4%/%'')+!5),+*&+!%--(41#%'+!5%/!:1%5*(!
#+0*(&)-(8!M/-1#+!5)!:1+&'+!0(*4+!$('*+66+*(!+00+''),%4+#'+!+&&+*+!-%*%''+*)22%'+!5%!
0+#(4+#)!)#0)%44%'(*)!Y-.+!4%7%*)!&)!&,)/1$$%#(!)#!-%&(!5)!)#0+2)(#)Z8!"#!&(&'%#2%3!$()3!?!
$*(6%6)/+!-.+!4(/'+!5)!:1+&'+!0(*4+!&)%#(!&+4$/)-+4+#'+!/B+&'*+4)22%2)(#+!5+/!
0+#(4+#(!$%*%0)&)(/(7)-(!5+//%!$*('+)#1*)%!#+/!6%46)#(!)#!-(*&(!5)!0+66*+3!'%#'(!$)F!-.+!
)!6%46)#)!&(#(!&(77+'')!-.+!5)!$+*!&[!'+#5(#(!%!&,)/1$$%*+!*)&$(&'+!-)'(-.)#)-.+!
+&(*6)'%#')!%5!($+*%!5+//B)441#)'>!)##%'%C!&+!:1+&'(!&)!*),+/%!%66%&'%#2%!)##(-1(!#+/!
6%46)#(!@&%#(A3!#+/!6%46)#(!-(#!5)0+'')!7+#+')-)!5+/!-)'(&-.+/+'*(!$(5(-)'%*)(!)/!5%##(!
-.+!&)!5+'+*4)#%!)#!:1+&'%!&)'1%2)(#+!#(#!$1N!$)F!+&&+*+!*)$%*%'(!+00)-%-+4+#'+8!

`%$/(,1%$0-%(,$0')+$-"%()0(&/(*#"%()
non
L1+&'(!?!1#!:1%5*(!$*(/)0+*%'),(!-.+!&)!,+*)0)-%!:1%#5(!&)!?!%,1'%!/%!4(*'+!5+/!QP<SPR!
5+)!$(5(-)')8!O)!5+&-*),+,%#(!-/%&&)-%4+#'+!0(*4+!$*)4)'),+!+!0(*4+!&+-(#5%*)+8!E%!
5+0)#)2)(#+!5)!0(*4+!@$*)4)'),+A!5+*),%!5%/!0%''(!-.+!#+//+!6)($&)+!&)!+*%#(!*)&-(#'*%')!)#!
%/-1#)!-%&)!"7X!%!/),+//(!7/(4+*1/%*+G!)#!&+71)'(3!&)!-%$e!!-.+!:1+//+!"7X!&)!'*(,%,%#(!#+//%!
4+46*%#%!7/(4+*1/%*+!&+4$/)-+4+#'+!%!-%1&%!5)!0+#(4+#)!5)!'*%$$)#73!+!#(#!%!-%1&%!5)!
1#B)441#(*+%''),)'>!&$+-)0)-%8!L1)#5)3!&)!?!)$(')22%'%!/%!$*+&+#2%!5)!1#!0%''(*+!
$+*4+%6)/)22%#'+!)#!-)*-(/(3!+!-)!&(#(!/%,(*)!-.+!#+!5+&-*),(#(!/%!$*+&+#2%8!\(41#:1+!
&')%#(!/+!-(&+3!?!4(/'(!$*(6%6)/+!-.+!/%!5+0)#)2)(#+!5)!7/(4+*1/(&-/+*(&)!0(-%/+!
&+74+#'%/+!&)%!&+4$/)-+4+#'+!,%/)5%!-(4+!5+&-*)2)(#+!%#%'(4($%'(/(7)-%3!+!-.+!/+!
+#')'>!#(&(/(7)-.+!-.+!&)!+&$*)4(#(!'*%4)'+!:1+&'(!')$(!5)!/+&)(#+!&)%#(!)#!*+%/'>!
4(/'+$/)-)8!T#!%/'*(!%&$+''(!)4$(*'%#'+!?!-.+!:1+&')!$%2)+#')3!&+!'*%$)%#'%')3!*+-)5),%#(!
#+/!KPR!5+)!-%&)G!1#%!5)%7#(&)!5)!^OkO3!:1)#5)3!?!4(/'(!)4$+7#%'),%!$+*-.[!&)!*)&-.)%!5)!
+&&+*+!+&-/1&)!5%//%!$(&&)6)/)'>!5)!+00+''1%*+!)/!'*%$)%#'(8!!

M#-.+!)#!:1+&'(!-%&(!/%!-(#(&-+#2%!5+//+!$%'(/(7)+!7+#+')-.+!.%!4(/'(!-%46)%'(!)/!
#(&'*(!4(5(!5)!,+5+*+!:1+&'%!$%'(/(7)%8!"#!+00+'')3!&)!?!,)&'(!-.+!)!6%46)#)!-(#!%/'+*%2)(#)!
7+#+')-.+!&(#(!:1+//)!-.+!5($(!)/!'*%$)%#'(!#(#!*+-)5),%#(3!)#!:1%#'(!)/!5)0+''(!&%*+66+!
)#'*)#&+-(!%//B(*7%#(!+&$)%#'%'(C!$%*%//+/%4+#'+3!:1+//)!-.+!'+#5(#(!%!$+*5+*+!)/!
'*%$)%#'(!&(#(!:1+//)!)#!-1)!#(#!-B?!1#!5)0+''(!7+#+')-(!%//%!6%&+3!+!D!71%*5%!-%&(!D!:1+//)!
-.+!.%##(!1#%!:1%/-.+!*)&$(&'%!%//%!'+*%$)%!)441#(&($$*+&&),%3!%!&177+*)*+!)/!*1(/(!5)!
-)'(-.)#+!+!)#0)%44%2)(#+!#+//%!$%'(7+#+&)!5)!:1+&'+!0(*4+8!!

"#!&+71)'(3!-)!&)%4(!%--(*')!-.+!1#%!:1('%!5+)!$%2)+#')!-(#!%/'+*%2)(#)!7+#+')-.+!$+*5+!
-(41#:1+!)/!'*%$)%#'(8!L1+&'(3!$+*-.[!)#!%/-1#)!5)!:1+&')!-%&)!/%!$*('+)#%!-(#,(/'%!?!
'('%/4+#'+!4%#-%#'+3!#(#!&)#'+')22%'%!Y5+/+2)(#)!'('%/)3!41'%2)(#)!&'($Z!+!:1)#5)!)/!
&)&'+4%!)441#)'%*)(!5+/!6%46)#(!#(#!*)-(#(&-+!-(4+!&+/0!:1+//%!&'+&&%!$*('+)#%!
$*+&+#'+!#+)!$(5(-)')!5+/!*+#+!'*%$)%#'%'(8!
Condizioni morbose che possono provocare una
a&)&'+!$()!)/!a1"3,$)0(-$*3",'$3!:1+//(!$)F!0*+:1+#'+3!-.+!)/!-/%&&)-(!-%&(!5)!0a1'%'C,'$)
#,")/"00")+'%#,"*#()()/"00")3")+'%#,",(Q)
GSF secondaria
Infezioni virali (HIV, epatite B)! M!$%*'+!/+!)#0+2)(#)!5%!l"h!+!
Farmaci (eroina, analgesici) lqh3!)#0%'')3!$+*!'1''+!/+!%/'*+!
,(-)!5)!:1+&'(!+/+#-(3!/%!-)0*%!?!
Neoplasie (linfomi, altre neoplasie)
$*($*)(!:1+&'(!&:1)/)6*)(!'*%!
Malattie congenite renali (oligonefronia, 4%&&%!0)/'*%#'+!+!4%&&%!5%!
ipoplasia segmentaria) 0)/'*%*+8!L1+&'(!7+#+*%!1#%!
Ridotta massa nefronica (agenesia renale &)'1%2)(#+!5)!)$+*0)/'*%2)(#+!
unilaterale)!
Uropatia ostruttiva
Reflusso vescico-ureterale
Obesit grave
Trapianto renale
-.+!-%1&%!5%##(!7/(4+*1/%*+!+!:1)#5)!$*('+)#1*)%8!

H+*!:1%#'(!*)71%*5%!/Bl"h3!+&)&'+!1#!:1%5*(!$%*')-(/%*+!-.+!&)!&,)/1$$%!#+)!$%2)+#')!l"hw3!
-.)%4%'(!-(//%$&)#7!7/(4+*1/($%'.o8!O)!,+5+!&($*%''1''(!#+7/)!%0*(%4+*)-%#)!#+7/)!O'%')!
T#)')8!!

V+*%$)%!

H+*!/%!'+*%$)%3!?!#+-+&&%*)(!$*)4%!
5+'+*4)#%*+!/%!-%1&%!5+//%!^OkO8!
b+//+!0(*4+!5%!&:1)/)6*)(!'*%!4%&&%!
#+0*(#)-%!+!4%&&%!5%!0)/'*%*+!/%!
'+*%$)%!4)7/)(*+!?!:1+//%!-(#!M\a<"!(!
&%*'%#)-)8!b+//+!0(*4+!-.+!&)!
&(&$+''%#(!&1!6%&+!)441#(/(7)-%3!&)!
)4$)+7%#(!&'+*()5)!+5!
)441#(&($$*+&&(*)8!!

A9 ^$,/()!,$%'+(,"#'7()
)
< ^/(4+*1/($%')%!%!5+$(&)')!4+&%#7)%/)!5)!"7M!
Sindromi cliniche associate alle
< ^/(4+*1/(#+0*)'+!$*(/)0+*%'),%!+#5(-%$)//%*+!(!$(&'<)#0+''),%!
< ^/(4+*1/(#+0*)')!4+46*%#(<$*(/)0+*%'),+!
principali forme di glomerulonefrite
< ^/(4+*1/(#+0*)'+!$*(/)0+*%'),%!+g'*%-%$)//%*+!
!
!
Sindrome Sindrome Anomalie Ematuria
!
nefrosica nefritica urinarie isolata
Sindromi cliniche associate alle -/+
`%$/(,1%$*(+,'#()")3(6$0'#')/(0"*&'"%')3')R&S)
Malattia a lesioni minime +++++ - ++

principali
GN membranosaforme ++++ di glomerulonefrite
aB!/%!0(*4%!5)!7/(4+*1/(#+0*)'+!$*)4)'),%!$)F!-(41#+!5+/!4(#5(8!O)!$1N!$*+&+#'%*+!-(#!
+ ++ -/+
5),+*&)!:1%5*)3!4%!$)F!0*+:1+#'+4+#'+!-(#!%#(4%/)+!1*)#%*)+!)&(/%'+3!4+#'*+!)/!$%2)+#'+!
Sindrome Sindrome Anomalie Ematuria
GS focale e segmentale +++ + ++ -/+
nefrosica nefritica urinarie isolata
Malattia a lesioni
Nefropatia minime
ad IgA +++++
++ -
+++ ++
++++ -/+
++++

GN membranosa
GN membranoproliferativa ++++
+++ +
+++ ++
++++ -/+
-/+
7(5+!5)!61(#%!&%/1'+8!!
GS focale e segmentale +++ + ++ -/+
GN proliferativa endocapillare + ++++ ++++ ++
M#-.+!/B+4%'1*)%!*)-(**+#'+!D!&$+&&(!%&&(-)%'%!%!+$)&(5)!)#0+''),)!D!$1N!+&&+*+!1#%!0(*4%!
5)!$*+&+#'%2)(#+!-/)#)-%!%66%&'%#2%!')$)-%G!/B+4%'1*)%!5%!#+0*($%')%!%5!"7M!?!')$)-%4+#'+!
Nefropatia ad IgA ++ +++ ++++ ++++
0'*+",'*&'#'-"3!-)(?!&)#-*(#%!%5!1#!+$)&(5)(!5)!0%*)#7)'+!+!0+66*+!Y4+#'*+!:1+//%!$(&'<
GN a semilune + ++++ ++++ -
&'*+$'(-(--)-%!?!6$0#L+",'*&'#'-"Z8!!
GN membranoproliferativa +++ +++ ++++ -/+
!
GN proliferativa endocapillare + ++++ ++++ ++

GN a semilune + ++++ ++++ -


La Nefropatia ad IgA, descritta
per la prima volta nel 1968, la
forma di glomerulonefrite
primitiva pi comune del mondo.
La glomerulonefrite da depositi di IgA una glomerulonefrite E una forma a patogenesi
con impegno prevalentemente mesangiale, che si manifesta anticorpo-mediata, nella quale i
soprattutto con ematuria. Questa pu essere sia macro che depositi immunologici si depo-
microscopica e si pu talora associare a proteinuria,
sitano nel mesangio. I depositi si
raramente nel range nefrosico.
Era una malattia un tempo scarsamente conosciuta anche formano in circolo, e rimangono
per il fatto che lematuria isolata era sovente attribuita a intrappolati a livello glomerulare
cause urologiche ed i pazienti non erano sottoposti a biopsia a causa di una alterata
renale. Da quando la pratica della biopsia renale si andata glicosilazione che ne altera la
estendendo anche allematuria isolata, la glomerulonefrite a clearance e che ne favorisce
depositi di IgA diventata la GN pi diffusa nel mondo.
Rappresenta il 30-50% delle glomerulonefriti in Asia, il 20-25%
luptake da parte delle cellule
in Europa ed il 5-10% negli Stati Uniti; tale differente mesangiali, facendo produrre
prevalenza in parte legata alle differenze nelluso della citochine che favoriscono la
biopsia renale cui abbiamo sopra accennato. proliferazione mesangiale.
!
"/!5+$(&)'(!4+&%#7)%/+!?!$(&&)6)/+!7*%2)+!%//%!$*+&+#2%!5)!*+-+''(*)!$+*!k-"!)#!&+5+!
4+&%#7)%/+8!b+/!SPR!5+)!-%&)!&)!*)&-(#'*%!1#!%14+#'(!5+//+!"7M!&)+*)-.+!+5!
)441#(-(4$/+&&(!-)*-(/%#')!-(#'+#+#')!"7M8!

V1''%,)%3!&)!-(#(&-(#(!%#-.+!+$,/()0(-$*3",'(G!+&&+!&)!$*+&+#'%#(!')$)-%4+#'+!)#!
$%2)+#')!-(#!5)0+'')!5+//B)441#)'>!41-(&%/+G!

< O"%"##'")-(%'"-")
< O$,C$)3');,$.*)
< U(##$-$%'#()1%-(,$0")
< !$,6$,")3')<-.$(*%('*Lh(*$-.3!-(&')'1)'(!5%!#+0*($%')%!%5!"7M3!%*'*%/7)+!+!
$(*$(*%!,%&-(/%*+G!&)!,+5+!4(/'(!&$+&&(!#+)!6%46)#)!+!#+7/)!%5(/+&-+#')8!V%/,(/'%!
$(&&(#(!+&&+*+!$*+&+#')!%#-.+!5)&'1*6)!7%&'*()#'+&')#%/)8!

!
H*+&+#'%2)(#+!\/)#)-%!
Modalit di presentazione clinica
I pazienti affetti da nefropatia ad IgA si presentano di solito con una di queste
sindromi cliniche:
!
Il 40-50% dei pazienti presenta uno o pi episodi di ematuria macroscopica,
di solito in concomitanza con eventi febbrili o infezioni respiratorie.

Il 30-40% dei pazienti presenta ematuria microscopica persistente


asintomatica e proteinuria di grado variabile.

Meno del 10% dei pazienti si presenta con un quadro clinico a tipo sindrome
nefritica acuta.

porpora di Schonlein-Henoch: la forma sistemica della malattia.


Determina nefropatia ad IgA e si verifica pi frequentemente nei bambini
che negli adulti. I pazienti affetti da Schonlein-Henoch manifestano
porpora, artralgie e coinvolgimento intestinale (vedi oltre).

Una modalit di presentazione pi rara quella di una sindrome nefrosica.


In questo caso, laspetto in microscopia ottica quello di una malattia a
lesioni minime ma con intenso deposito mesangiale di IgA
allimmunofluorescenza. !

!
Decorso clinico
_+-(*&(!

La funzione renale peggiora progressivamente in circa il 40% dei


pazienti, e circa la met di questi volgono verso linsufficienza
renale terminale in circa 20 anni. Fattori predittivi di una
prognosi sfavorevole sono la presenza di insufficienza renale al
momento della diagnosi, una microematuria persistente, una
proteinuria>1 g/die, lo sviluppo di pertensione o lesioni severe alla
biopsia renale. Il 5% dei pazienti pu sviluppare unipertensione
maligna.

Depositi secondari di IgA si possono osservare nelle malattie


epatiche croniche, nella dermatite erpetiforme, nella psoriasi,
nella spondilite anchilosante, nel morbo celiaco, nelle malattie
infiammatorie croniche dellintestino, nei carcinomi, nella
gammapatia monoclonale ad IgA, nellnfezione da HIV e nella
micosi fungoide.
!

V+*%$)%! Terapia
Studi recenti relativi al ruolo degli ACE inibitori e degli steroidi
b+)!-%&)!-(#!$*('+)#1*)%!&)!)4$)+7%#(!M\a<"!+!&%*'%#)3!&+!/%!$*('+)#1*)%!?!/)+,+8!O+!/%!
nella nefropatia ad IgA hanno modificato la trerapia della
Nefropatia ad IgA:
$*('+)#1*)%!?!4%77)(*+!5)!W7U5)+3!&)!1&%#(!7/)!&'+*()5)8!O+!&)!,%!(/'*+!)!K!73!&)!1')/)22%#(!7/)!
)441#(&($$*+&&(*)8!
Inibitori dellEnzima di Conversione dellAngiotensina/e o sartanici
Si sono dimostrati pi efficaci degli altri anti-ipertensivi nel !
ritardare la progressione verso linsufficienza renale e nel ridurre la
proteinuria, e vanno somministrati a tutti i pazienti, a prescindere dalla
presenza di ipertensione e dal grado di proteinuria. !

!
Se proteinuria> 1g/die:
Cicli di Steroidi
!
Riducono la perdita proteica nei soggetti che si presentano con grave
proteinuria, alcuni dati suggeriscono un effettivo vantaggio nel preservare
la funzione renale a lungo termine. !
Se proteinuria> 3g/die:
Cicli di Steroidi da soli o in associazione ad immunosoppressori
Gli immunosoppressori sono indicati soprattutto se vi
deterioramento della funzione renale.
GLOMERULONEFRITE PROLIFERATIVA
ENDOCAPILLARE
`%$/(,1%$*(+,'#()6,$%'+(,"#'7")(*3$-"6'%%",()

L1+&'%!0(*4%!?!$+*!-+*')!
%&$+'')!&)4)/!%//%!#+0*($%')%!%5!
"7M3!4%!)/!5+-(*&(!+!
/B+$)5+4)(/(7)%!&(#(!
-(4$/+'%4+#'+!5),+*&)8!L1+&'%!
?!/%!0(*4%!$*+-+5+#'+4+#'+!
#('%!-(#!)/!#(4+!5)!
&%$/(,1%$*(+,'#()6$0#L
0#,(6#$-$--'-")Y$(&'<
0%*)#7)')-%Z8!

EB%&$+''(!)&'(/(7)-(!?!
-%*%''+*)22%'(!5%!1#B)#'+#&%!
A forte ingrandimento evidente l'intensa$*(/)0+*%2)(#+!4+&%#7)%/+!+5!+#5('+/)%/+!%//B)#'+*#(!5+/!
ipercellularit glomerulare, in
cui sono riconoscibili numerose cellule infiammatorie endoluminali come
7/(4+*1/(3!-(#!)#0)/'*%2)(#+!5)!7*%#1/(-)')!+!-+//1/+!
i leucociti polimorfonucleati e cellule monocitarie.
4(#(#1-/+%'+3!*+&$(#&%6)/)!5+/!5%##(8!

M#-.+!/%!7/(4+*1/(#+0*)'+!$*(/)0+*%'),+!+#5(-%$)//%*+!&)!
$*+&+#'%!7+#+*%/4+#'+!-(#!1#B+4%'1*)%!)&(/%'%G!%!
5)00+*+#2%!5+//B+4%'1*)%!5+//%!#+0*($%')%!%5!"7M3!-.+!?!
')$)-%4+#'+!&)#0%*)#7)')-%3!:1+//%!5%!^Ha\!&)!$*+&+#'%!
7+#+*%/4+#'+!ALD)0(##'/"*(!5($(!/B+$)&(5)(!0%*)#7)')-(!
+5!?!:1)#5)!$(&'<0%*)#7)')-%8!L1+&'(3!$+*-.[!/%!^Ha\!?!
1#%!$%'(/(7)%!7/(4+*1/%*+!5%!5+$(&)'(!5)!'//1*$-$/6%(00'3!+!$+*-.[!:1+&'+!
4%-*(4(/+-(/+!&)!0(*4)#(!?!#+-+&&%*)(!-.+!&)!&,)/1$$)!-(4$/+'%4+#'+!/%!*)&$(&'%!
)441#)'%*)%!5+//B(&$)'+8!

L1+&'%3!$+*N3!?!/%!0(*4%!-(#-/%4%'%3!(*4%)!
%66%&'%#2%!*%*%!#+//B%46)'(!5+//%!4+5)-)#%!
7+#+*%/+!D!&+66+#+!%#-(*%!*+/%'),%4+#'+!
0*+:1+#'+!)#!%46)'(!$+5)%'*)-(8!\)N!-.+!&)!,+5+!
0*+:1+#'+4+#'+3!)#,+-+3!&(#(!/+!/'-,$(/"#1,'()
6$0#L'*+(##'7(9!H+*'%#'(3!/%!4(5%/)'>!5)!
$*+&+#'%2)(#+!5+//%!^Ha\!$1N!+&&+*+G!

<<'*3,$/()*(+,'#'-")"-1#"3!
$*+&+#'%2)(#+!%-1'%!-(#!6%46)#(!
(/)71*)-(3!-(#!+5+4%!5+/!,(/'(3!
4%-*(+4%'1*)%3!1#%!-+*'%!:1('%!5)!$*('+)#1*)%!+5!)$+*'+#&)(#+8!)
< S*$/"%'()1,'*",'()I/$3(0#")/'-,$(/"#1,'"3!'%/,(/'%!%#-.+!/)+,+!$*('+)#1*)%Z)

9/'*+!%//B)#0)/'*%2)(#+!
/+1-(-)'%*)%3!%#-.+!
/B%''),%2)(#+!4%&&),%!5+/!
-(4$/+4+#'(!%5!($+*%!
5+7/)!)441#(-(4$/+&&)!?!
1#!%&$+''(!
)4$(*'%#')&&)4(!#+/!
L'utilizzo di anticorpi monoclonali, 5%##(!7/(4+*1/%*+8!O+!
con metodo immunoistochimico, %#5)%4(!%!0%*+!
ha permesso di quantizzare meglio
l'entit e le caratteristiche delle 1#B)441#(0/1(*+&-+#2%!
cellule infiammatorie coinvolte nel $+*!)/!\K3!,+5)%4(!-.+!/+!
danno glomerulare. L'anticorpo 4+46*%#+!6%&%/)!&(#(!
contro l'antigene comune
leucocitario conferma la massiva
infiltrazione di queste cellule nel
flocculo glomerulare.
&')$%'+!5)!0*%2)(#+!-(4$/+4+#'%*+3!%!'+&')4(#)%*+!/%!4%&&),%!%''),%2)(#+!5+/!&)&'+4%!5+/!
-(4$/+4+#'(8!"#0%'')3!)#!:1+&'%!$%'(/(7)%!?!')$)-(!)/!*)&-(#'*(!5)!1#%!
'6$-$/6%(/(*#(/'"!5%!-(#&14(3!-.+!?!)#,+-+!%&&(/1'%4+#'+!%&&+#'+!#+//%!#+0*($%')%!
%5!"7M!Y+!:1)#5)!?!1#!61(#!-*)'+*)(!5)!5)&')#2)(#+Z8!"/!*)+#'*(!5+//%!-(4$/+4+#'+4)%!#+/!
*%#7+!#(*4%/+!'+&')4(#)%!/%!*+4)&&)(#+!5+//%!4%/%'')%8!!

a2)(/(7)%!+!$%'(7+#+&)!

L1+&'%!0(*4%!5)!7/(4+*1/(#+0*)'+!)441#(4+5)%'%!?!$+*!/(!$)F!&+-(#5%*)%!%!$*(-+&&)!
)#0+''),)8!E(!O'*+$'(-(--(!!<+4(/)')-(!5)!7*1$$(!M3!%7+#'+!5)!0%*)#7('(#&)//)')!+!
&-%*/%'')#%3!?!/B%7+#'+!'*%5)2)(#%/4+#'+!-.)%4%'(!)#!-%1&%3!4%!#(#!?!/B1#)-(!-.+!$1N!
-%1&%*+!1#%!$%'(/(7)%!5+/!7+#+*+G!&(#(!)#0%'')!-()#,(/')!%/'*)!6%''+*)!Y+&G!*)-]+''&)%+Z3!
,)*1&!+!$+*&)#(!$*('(2()8!E%!$%'(7+#+&)!?!%66%&'%#2%!&+4$/)-+G!5+'+*4)#%')!%#')7+#)!
6%''+*)-)U,)*%/)U$*('(2(%*)!Y$+*!+&+4$)(3!$+*!7/)!&'*+$'(-(--.)!&)!*)')+#+!+&&+*+!-()#,(/'%!
/%!0#,(6#$W'*"0'Z3!:1%#5(!$*+&+#')!)#!7*%#5)!:1%#')'>!)##+&-%#(!1#%!*)&$(&'%!
)441#)'%*)%!+&'*+4%4+#'+!,)(/+#'%3!&($*%''1''(!#+/!6%46)#(3!+!%!4%77)(*!*%7)(#+!
:1%#5(!#(#!,)+#+!)#'*%$*+&%!1#%!%5+71%'%!'+*%$)%!%#')6)(')-%8!H+*'%#'(3!-(/!4(#'%*+!
5+//%!*)&$(&'%!)441#)'%*)%!D!$*(-+&&(!-.+!*)-.)+5+!-)*-%!I!&+'')4%#+!D!&)!.%!/%!
0(*4%2)(#+!5)!1#%!7*%#5)&&)4%!:1%#')'>!5)!%#')-(*$)!-.+!,%##(!%!-(4$/+&&%*&)!-(#!
/B%#')7+#+!-.+!&)!'*(,%!&)%!/)6+*(!)#!-)*-(/(3!&)%!5+$(&)'%'(!&1//%!4+46*%#%!6%&%/+!
7/(4+*1/%*+!)#!*%7)(#+!5+//%!&1%!+/+,%'%!/)$(0)/)-)'>8!L1)#5)3!&)!0(*4%#(!
)441#(-(4$/+&&)!)#!&+5+!7/(4+*1/%*+3!+!:1+//)!-)*-(/%#')!,%##(!%!5+$(&)'%*&)!&1//%!
4+46*%#%!7/(4+*1/%*+!%!-%1&%!5+)!$*(-+&&)!5)!0)/'*%2)(#+8!M!:1+&'(!$1#'(3!)/!5%##(!
7/(4+*1/%*+!?!4+5)%'(!&)%!5%//%!-%&-%'%!-(4$/+4+#'%*+!Y%''),%'%!'*%4)'+!/%!,)%!-/%&&)-%!
%5!($+*%!5+7/)!)441#(-(4$/+&&)Z3!&)%!5%)!/+1-(-)')3!*)-.)%4%')!&1/!/1(7(!5%//+!
%#%0)/('(&&)#+!+!%''),%')!7*%2)+!%)!/(*(!*+-+''(*)!$+*!k-8!!

_+-(*&(!

aB!+&'*+4%4+#'+!)4$(*'%#'+!*)-(#(&-+*+!$*(#'%4+#'+!1#%!7/(4+*1/(#+0*)'+!$(&'<
)#0+''),%C!)#0%'')3!&+!#+)!6%46)#)!/%!$*(7#(&)!?!('')4%!D!-(#!*+4)&&)(#+!-(4$/+'%!(''+#1'%!
)#!7+#+*+!+#'*(!;!4+&)3!#+7/)!%51/')!%")6,$&*$0')i)6(&&'$,(G!)#!(/'*+!)/!SPR!5+)!-%&)!)/!
:1%5*(!-*(#)-)22%!-(#!$*(7*+&&),(!5+'+*)(*%4+#'(!5+//%!01#2)(#+!*+#%/+8!T#!)#5)-%'(*+!
5+//%!$(&&)6)/+!+,(/12)(#+!-*(#)-%!?!/%!$+*&)&'+#2%!5+//%!$*('+)#1*)%8!\.)%*%4+#'+3!
/B)#'*(512)(#+!5+//%!'+*%$)%!%#')6)(')-%!$+*!/+!0%*)#7('(#&)//)')!.%!*),(/12)(#%'(!/%!-/)#)-%!
5)!:1+&'+!0(*4+G!(77)!)!6%46)#)!,+#7(#(!'*%''%')!$*+-(-+4+#'+!:1%#5(!&,)/1$$%#(!1#%!
0%*)#7('(#&)//)'+3!%#-.+!&+4$/)-+!&1!6%&+!+4$)*)-%!&+#2%!+00+''1%*+!'%4$(#+!+5!
%#')6)(7*%44%8!H+*!:1+&'(3!)!6%46)#)!'+#5(#(!%!4(#'%*+!*)&$(&'+!)441#)'%*)+!4(/'(!
$)F!4(5+&'+!%!-%1&%!5+//%!$*+&+#2%!5)!4)#(*)!:1%#')'>!5)!%#')7+#+3!+!7/)!
)441#(-(4$/+&&)!&)!0(*4%#(3!4%!'*)/'01,")/$%#$)/'*$,(G!:1)#5)3!(77)7)(*#(!#(#!?!
-.+!/%!0*+:1+#2%!5+//+!7/(4+*1/(#+0*)')!$(&'<)#0+''),+!&)%!*+%/4+#'+!5)4)#1)'%8!\)N!-.+!?!
5)4)#1)'(!?!/%!+,(a1(*2")3(&%')(6'0$3')-$*-%"/"#'!-(#!4%-*(+4%'1*)%8!!

E%!5)%7#(&)!?!$)F!&+4$/)-+!5($(!1#!+$)&(5)(!5)!&-%*/%'')#%3!$+*-.[!)#!:1+&'(!-%&(!&(#(!
$*+,)&')!+&%4)!5+//+!1*)#+!%!51+!&+'')4%#+!5%//B+$)&(5)(3!+!:1)#5)!?!0%-)/+!)/!*)&-(#'*(!5)!
1#%!4(5+&'%!4)-*(+4%'1*)%8!

V+*%$)%!

aB!1#%!'+*%$)%!5)!&1$$(*'(3!$+*-.[!&(/)'%4+#'+!/%!4%/%'')%!,%!)#!*+4)&&)(#+!&$(#'%#+%8!
"$+*'+#&)(#+!+!&(,*%--%*)-(!,(/+4)-(!$(&&(#(!+&&+*+!'*%''%')!-(#!5)1*+')-)!+5!%/'*)!
0%*4%-)!%#')<)$+*'+#&),)3!&+4$*+!5%!1&%*+!-(#!%''+#2)(#+8!M/-1#)!$%2)+#')3!#(#(&'%#'+!/%!
'+*%$)%!+!/%!*)&(/12)(#+!5+/!:1%5*(3!-(#')#1%#(!%5!+&&+*+!)$+*'+&)8!

`%$/(,1%$*(+,'#()/(/C,"*$6,$%'+(,"#'7")

M#-.+!:1+&'%!?!1#%!0(*4%!$*(/)0+*%'),%3!:1)#5)!%&&(-)%'%!%5!(/"#1,'"G)06(00$)
/'-,$0-$6'-"9)O)!'*%''%!$+*N!5)!1#%!0(*4%!%!$(#'+3!-(#!%&$+'')!$*(/)0+*%'),)!-.+!
-(+&)&'(#(!-(#!1#!)&$+&&)4+#'(!5+//%!4+46*%#%!6%&%/+G!:1+&'(!&$)+7%!$+*-.[!4(/')!5)!
:1+&')!&(77+'')!&)!$*+&+#')#(!%#-.+!-(#!1#%!0'*3,$/()*(+,$0'-")3')1*")-(,#")
Glomerulonefrite membranoproliferativa
'/6$,#"*2"9))

Lassociazione della glomerulonefrite membranoproliferativa con numerose


entit nosologiche hanno suggerito che non si tratti di ununica entit
etiopatogenetica. Tuttavia il recente riconoscimento della relazione causale
tra linfezione da virus C e la glomerulonefrite membranoproliferativa
suggerisce che questo virus sia coinvolto in almeno il 60% delle forme
prima ritenute idiopatiche. Sulla base delle differenze istopatologiche si
riconoscono diverse varianti:
Tipo I: caratterizzata da depositi
mesangiali e subendoteliali.

Tipo II: (malattia a depositi densi) caratterizzata da depositi lineari


interrotti nella lamina densa della membrana basale.

Tipo III: una variante pi rara, caratterizzata da caratteristiche comuni


alla tipo I e alla tipo II o dallaccumulo di nuovo
materiale organizzato in strati a livello della membrana basale.
)
977)!&)!4+''+!0(*'+4+#'+!)#!5166)(!/B+&)&'+#2%!5+/!')$(!"""8!!

E%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%!?!4(/'(!)4$(*'%#'+!$()-.[!#+/!;PR!5+)!-%&)!
&)!%&&(-)%!"%%5'*+(2'$*()3")h;jQ!#+)!$%2)+#')!-(#!+$%')'+!\!#('%!?!&+4$*+!6+#+!*)-+*-%*+!
/%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%3!+!#+)!$%2)+#')!-(#!7/(4+*1/(#+0*)'+!
4+46*%#($*(/)0+*%'),%!6)&(7#%!&+4$*+!*)-+*-%*+!/B)#0+2)(#+!5%!l\h8!

H%'(7+#+&)!

E%!0(*4%!5)!')$(!"!?!/%!$)F!0*+:1+#'+!)#!-/)#)-%!+!$1N!%&&(-)%*&)!%!5),+*&+!-(#5)2)(#)!
-/)#)-.+G!

< ;,'$&%$C1%'*(/'")'*)-$,0$)3')(6"#'#();)
< ;,'$&%$C1%'*(/'")0(*2")(6"#'#();)I_'*+$/'G)%(1-(/'")%'*+"#'-.(G)/"%"##'()
"1#$'//1*'J)
O+!&)!*)&-(#'*%!1#%!7/(4+*1/(#+0*)'+!4+46*%#($*(/)0+*%'),%3!?!)4$(*'%#'+!
*)-.)+5+*+!)/!5(&%77)(!5+//+!-*)(7/(61/)#+!-.+3!&+!$(&)'),(3!5+,+!)#51*-)!%!
*)-+*-%*+!/%!4%/%'')%!5)!6%&+3!&)%!+&&%!/B+$%')'+!\!(!1#B%/'*%!-(#5)2)(#+!-.+!$1N!
-%1&%*+!-*)(7/(61/)#+4)%8!
< _1610)(,'#(/"#$0$)0'0#(/'-$)
< O"%"##'()%'*+$6,$%'+(,"#'7()-,$*'-.()
< R*+(2'$*()3")hKj)
< S%#,()'*+(2'$*')C"##(,'-.()I(0Q)(*3$-",3'#'J)()7',"%')
E%!-%1&%3!#+)!-%&)!%&&(-)%')!%5!l\h3!&+46*%!:1)#5)!+&&+*+!)5+#')0)-%6)/+!#+//%!
-,'$&%$C1%'*(/'"9)E+!-*)(7/(61/)#+3!%!,(/'+!5)*+''%4+#'+!-(4$/+&&%'+!%/!,)*1&!\3!&)!
5+$(&)'%#(!%/!/),+//(!7/(4+*1/%*+8!
Si ritiene che la glomerulonefrite membrano-
proliferativa sia provocata dalla deposizione di
immunocomplessi a livello glomerulare, in
particolare sul versante interno sottoendoteliale
della membrana basale, oltre che a livello
mesangiale, con attivazione delle cellule
mesangiali ed espansione della matrice
mesangiale, che stimola la interposizione del
mesangio fino alla periferia del capillare
glomerulare in sede sottoendoteliale, con
conseguente "duplicazione" della stessa (doppio
contorno della MBG). !
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3(&%')'//1*$-$/6%(00'3!-.+!&)!'*%51-+!)#!1#B%''),%2)(#+!-*(#)-%!5+/!-(4$/+4+#'(3!)!
-1)!/),+//)!&(#(!)#0%'')!0/1''1%#')!)#!:1+&'%!$%'(/(7)%8!!

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,+*)!+!$*($*)!%1'(%#')-(*$)!-.+3!6/(--%#5(!7/)!)#)6)'(*)!0)&)(/(7)-)!5+/!-(4$/+4+#'(3!
5+'+*4)#%#(!1#B%''),%2)(#+!5+//%!-%&-%'%!-(4$/+4+#'%*+!%''*%,+*&(!/%!,)%!%/'+*#%'),%8!

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5)00)-)/+!5%!-1*%*+G!/%!'+*%$)%!?!)#0%'')!*),(/'%!%//%!+*%5)-%2)(#+!5+/!,)*1&!\3!(6)+''),(!#(#!
&+4$*+!*%77)1#7)6)/+8!"#(/'*+3!/B)#'+*0+*(#!1')/)22%'(!$+*!/%!'+*%$)%!5+//B)#0+2)(#+!5%!l\h!
.%!)/!$*(6/+4%!5+//B)#512)(#+!5+//%!$*('+)#1*)%3!$+*!-1)!)/!'*%''%4+#'(!&'+&&(!$1N!
%77*%,%*+!)/!:1%5*(!*+#%/+8!

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3(%%")-"601%")3')K$T/"*9)_%!:1+&'(!0+#(4+#(!$*(/)0+*%'),(!#%&-+!1#%!/+&)(#+!5+/!
'1''(!$%*')-(/%*+3!/%!0(/'%1*"9))

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'%/,(/'%!-(#!1#!:1%5*(!&)4)/+!%//%!&)#5*(4+!#+0*)')-(8!\)N!-.+!5+'+*4)#%!)/!:1%5*(!
-/)#)-(3!-(41#:1+3!#(#!?!'%#'(!/B%/'+*%2)(#+!5+/!&+5)4+#'(3!:1%#'(!$)1''(&'(!'%),"6'3$)
3(-%'*$)3(%%")+1*2'$*(),(*"%(3!'%#'(!-.+!:1+&'%!0(*4%!,)+#+!%#-.+!5+0)#)'%!
@7/(4+*1/(#+0*)'+!*%$)5%4+#'+!$*(7*+&&),%A8!

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&'15)!5)!)441#(0/1(*+&-+#2%G!

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+&'+#5+*&)!%#-.+!%/!6$%/$*(G!)#!:1+&'(!1/')4(!-%&(!/%!4%/%'')%!$*+#5+!)/!#(4+!
5)!<'*3,$/()3')`$$36"0#1,(G)+!/%!$*+&+#2%!5)!+4('')&)!-)!$1N!)#5)*)22%*+!#+//%!
5)%7#(&)9)"/!')$)-(!:1%5*(!%//B)441#(0/1(*+&-+#2%!?!:1+//(!%!@+1/$)3')0'&",(##"A8)
)
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&+4)/1#+!$1N!*%$$*+&+#'%*+!1#%!0%&+!%--+/+*%'%!+!*%$)5%4+#'+!$*(7*+&&),%!5)!
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&+4)/1#+8!EB%#5%4+#'(!-/)#)-(!?!:1+//(!')$)-(!5+//%!7/(4+*1/(#+0*)'+!%!&+4)/1#+!
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$(&&)%4(!%,+*+!+4('')&)3!)#!:1%#'(!/+!,%&-1/)')!&)&'+4)-.+!-()#,(/7(#(!
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;.1,&L<#,"1008!b+//%!t+7+#+*!/B)#'+*+&&%4+#'(!*+#%/+!?!0*+:1+#'+!4%!#(#!(66/)7%'(*)(C!
)!$%2)+#')!5)!&(/)'(!.%##(!1#%!&'(*)%!5)!)#0+2)(#)!*)-(**+#')!5+//+!,)+!%+*++!&1$+*)(*)!-.+!
#(#!$%&&%#(8!"/!*)&-.)(!$*)#-)$%/+!?!1#!7*%,+!-()#,(/7)4+#'(!$(/4(#%*+3!-(#!4%&&),+!
+4(**%7)+!+!:1%5*)!5)!M`_O8!H+*!:1%#'(!*)71%*5%!/%!\.1*7<O'*%1&&3!+&&%!&)!%--(4$%7#%!
%5!%&4%!7*%,+3!&)#1&)'+U*)#)'+!-*(#)-%!+5!+(&)#(0)/)%8!b+//%!t+7+#+*!&)!'*(,%#(!
')$)-%4+#'+!-LS=;S)Y%#')<$*('+%&)!KZ3!4+#'*+!#+//%!\.1*7<O'*%1&&!&)!$(&&(#(!'*(,%*+!&)%!
$<Mb\M!-.+!-<Mb\M3!4%!')$)-%4+#'+!&)!'*(,%#(!)!6LS=;S)Y%#')<XH9Z8!

E%!'+*2%!0(*4%!?!/%!/'-,$6$%'"*&'$'#(3!1#%!0(*4%!,%&-1/)')-%!-.+!)#'+*+&&%!
6,(7"%(*#(/(*#())/!*+#+8!!
La vasculite dei piccoli vasi
tipicamente caratterizzata da una
necrosi massiva della parete vascolare
con infiltrati infiammatori intra e
perivascolari. Le lesioni di necrosi del
flocculo e di proliferazione extracapillare
sono assai variabili come intensit e
diffusione da caso a caso o spesso
all'interno di un singolo caso. Alla
necrosi massiva si associa abitualmente
una proliferazione extracapillare diffusa
e circonferenziale, con quadro clinico di
insufficienza renale a rapida
progressione. !
_%!#('%*+!-.+!/%!7/(4+*1/(#+0*)'+!$1N!%#-.+!+&&+*+!)/!:1%5*(!5B+&(*5)(!5)!1#%!5)!:1+&'+!
,%&-1/)')C!)#(/'*+3!'1'')!)!$%2)+#')!-(#!,%&-1/)')!&(#(!'+#1')!&(''(!-(#'*(//(!$+*)(5)-%4+#'+!
-(#!+&%4)!,%*)3!'*%!-1)!%#-.+!7/)!+&%4)!5+//+!1*)#+!Y$(-(!-(&'(&)3!&+4$/)-)Z3!-.+!
$+*4+''(#(!5)!)#5),)51%*+!$*+-(-+4+#'+!1#!+,+#'1%/+!5%##(!*+#%/+8!

_+-(*&(!

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)#!'+4$(!/%!5)%7#(&)!$()-.[!)!&+7#)!5)!5+'+*)(*%4+#'(!*%$)5(!5+//%!01#2)(#+!*+#%/+!
Y#%1&+%3!,(4)'(3!4)%/7)+3!4%/+&&+*+Z!,+#7(#(!0%-)/4+#'+!)#'+*$*+'%')!-(4+!&)#'(4)!
)#0/1+#2%/)8!"!$%2)+#')!$+*N!-(#')#1%#(!%!&'%*!4%/+G!%!:1+&'(!$1#'(!7/)!+&%4)!5+/!&%#71+!
+,)5+#2)%#(!7)>!%2('+4)%!+!-*+%')#)#+4)%!+/+,%'%!+!5)!-(#&+71+#2%!?!+&'*+4%4+#'+!
5)00)-)/+!)#'+*,+#)*+!-(#!+00)-%-)%8!L1+&')!$%2)+#')3!:1)#5)3!,%##(!)#-(#'*(!%//%!5)%/)&)3!&+!
#(#!%55)*)''1*%!%//B+g)'1&8!O+!&)!)#'+*,)+#+!$*+-(-+4+#'+3!$+*N3!$(&&)%4(!&%/,%*+!/%!:1('%!
5)!7/(4+*1/)!%#-(*%!#(#!-()#,(/'%8!d!&'%'(!5)4(&'*%'(!-.+!/%!-'-%$+$0+"/'3().%!1#%!-+*'%!
+00)-%-)%!#+/!0%*!*)+#'*%*+!/+!&+4)/1#+3!:1%#5(!%#-(*%!#(#!&(#(!&-/+*(')-.+G!
$*(6%6)/4+#'+3!:1+&'(!?!5(,1'(!%/!&1(!+00+''(!-)'(&'%')-(8!d!4(/'(!,+*(&)4)/+!-.+!/%!
/+&)(#+!5+//%!&+4)/1#%!&)%!1#%!&(*'%!5)!-.(%$'3(3!-)(?!1#!'+#'%'),(!%6#(*4+!5)!*)$%*%*+!
Prognosi
1#!+&'+&(!5%##(!-.+!&)!,+*)0)-%!)#!'+4$)!+&'*+4%4+#'+!*%$)5)8!!

La glomerulonefrite da anticorpi anti-membrana non trattata ha una


prognosi pessima sia quoad vitam che per quanto riguarda la funzione
renale. Nei pazienti trattati, la funzione renale migliora in quelli con
creatininemia < 600 mol/L allesordio, mentre la maggior parte di quelli
con creatininemia pi elevata necessiter della dialisi. La prognosi
peggiore nei pazienti con emorragia polmonare, che rappresenta la
principale causa di morte.

Circa il 75% dei pazienti con forme pauci-immuni ANCA-associate va in


remissione, ed il 43% di questi ancora in remissione dopo 4 anni. Il
miglior fattore predittivo della perdita di funzione renale anche in questo
caso il valore della creatinina allesordio. Tuttavia, alcuni pazienti che
necessitano di dialisi allesordio rispondono bene alla terapia; pertanto la
dialisi non rappresenta in questo caso una controindicazione al trattamento.

Terapia !
H*)4%!5)!)#)2)%*+!-(#!)!6(/)!5)!-)-/(0(&0%4)5+!&+*,+3!$+*!4('),)!$*+-%12)(#%/)!+!/+7%/)3!/%!
CORTICOSTEROIDI+CICLOFOSFAMIDE
3$-1/(*#"2'$*()C'$6#'-")3')1*)a1"3,$)-.()&'10#'+'-.')%5'/6'(&$)3')a1(0#$)+",/"-$8!
H+*'%#'(3!/+!0(*4+!%!&+4)/1#+!D!%#-.+!&+!4(/'(!%77*+&&),+!D!&(#(!5%!6)($&)%*+8!

Il solo esame importante per la prognosi il livello di


creatinina al momento della diagnosi. Pertanto la
diagnosi precoce il maggior determinante della
sopravvivenza sia dei reni che della vita del
paziente. Uninsufficienza renale che richieda la
dialisi non una controindicazione al trattamento. !

^/(4+*1/(#+0*)'+!E1$)-%!
"/!EaO!?!1#%!4%/%'')%!$)1''(&'(!0*+:1+#'+!+!)/!*+#+!?!1#(!5+7/)!(*7%#)!$)F!0*+:1+#'+4+#'+!
-()#,(/')G!)/!;P<=PR!5+)!$%2)+#')!-(#!EaO!&,)/1$$%#(!)#'+*+&&%4+#'(!*+#%/+!+!/%!
7/(4+*1/(#+0*)'+!$1N!+&&+*+!)/!:1%5*(!5B+&(*5)(8!L1)#5)3!5%/!$1#'(!5)!,)&'%!-/)#)-(!
%66)%4(!51+!$*(6/+4)G!

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6,'/")/"*'+(0#"2'$*(9)

"#!:1+&'(!-%&(!#(#!?!5)00)-)/+3!)#!:1%#'(!+&)&'(#(!-*)'+*)!6+#!5+0)#)')8!T#(!&'*14+#'(!
0(#5%4+#'%/+!?!/%!*)-+*-%!5+7/)!MbM!%!')'(/(!*)/+,%#'+!Y)#!$%*')-(/%*+!5+7/)!%#')<5&_bM!
#%'),(Z3!4%*]+*&!4(/+-(/%*)!5+//%!4%/%'')%8!

< V'"&*$0#'-",()6,(-$-(/(*#()%5'*#(,(00"/(*#$),(*"%()*(%)6"2'(*#()-$*)_4<)
*$#$9)

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-()#,(/7)4+#'(!*+#%/+!-%*%''+*)&')-%4+#'+!#+/!&+5)4+#'(!&)!'*(,%!5)!'1''(G!$*('+)#+3!
+*)'*(-)')3!/+1-(-)')3!-)/)#5*)8!a&)&'(#(!$()!:1%5*)!&014%')!(!%#-.+!#+0*(&)!4(/'(!
)4$(*'%#')8!b+)!$%2)+#')!-(#!EaO!/%!5)%7#(&)!5+//B)#'+*+&&%4+#'(!*+#%/+!?!'%/4+#'+!
)4$(*'%#'+!-.+!/B)#5)-%2)(#+!%//%!6)($&)%!&)!$(#+!%#-.+!)#!$*+&+#2%!5)!$)--(/+!%/'+*%2)(#)!
5+/!&+5)4+#'(!D!%!5)00+*+#2%!5)!:1%#'(!%--%5+!#+//%!$+*&(#%!#(*4%/+3!)#!-1)!/%!6)($&)%!&)!
Esami di laboratorio
0%!&(/(!&+!+&)&'+!1#B%/'+*%2)(#+!5)!1#!-+*'(!$+&(8!!

a&%4)!5%!*)-.)+5+*+!

Esami di funzionalit renale (creatinina, azotemia, creatinina


clearance)!
Esame delle urine standard e analisi del sedimento, proteinuria
24h
Indici di attivit di malattia: ANA (anti-dsDNA), complemento (C3,
C4, CH50), VES, proteina C reattiva (PCR). Livelli elevati di anti-
dsDNA, di VES e bassi livelli di C3 e C4 sono associati con
glomerulonefrite in fase di attivit, specie nelle forme proliferative.

La nefrite lupica si associa in genere con una riduzione del filtrato


del 30%, una proteinuria maggiore di 1g e una biopsia renale con
segni di nefrite attiva.
!

\/%&&)0)-%2)(#+!

"/!EaO!?!1#%!4%/%'')%!/$%#$)-$/6%(00")3"%)61*#$)3')7'0#"),(*"%(3!)#!-1)!&)!*)-(#(&-(#(!
&(&'%#2)%/4+#'+!&+)!:1%5*)!-(4$/+'%4+#'+!5),+*&)G!/+!$*)4+!:1%''*(!-/%&&)!5+&-*),(#(!
:1%5*)!5)!7/(4+*1/(#+0*)'+!$*(/)0+*%'),%!-(#!7*%,)'>!5),+*&%8!!

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7/(6%/+8!!

!
! World Health Organization Classification of Lupus Nephritis
Classe I: la biopsia renale rivela un rene essenzialmente normale.
!
Non c evidenza clinica di malattia.
Classe II: Glomerulonefrite mesangiale
Classe IIA: Glomerulonefrite proliferativa mesangiale lieve
MO: Lipercellularit mesangiale lieve o assente.
IF: I depositi immunologici sono confinati al mesangio.
ME: I depositi immunologici sono confinati al mesangio
Classe IIB: Glomerulonefrite proliferativa mesangiale moderata
MO: Ipercellularit mesangiale
confinata alle aree centrolobulari ed
assenza di infiltrati, necrosi o sclerosi.
IF: I depositi immunologici sono
confinati al mesangio
ME: I depositi immunologici sono
confinati al mesangio

Manifestazioni cliniche: Alterazioni


urinarie, ematuria, proteinuria.
World Health Organization Classification of Lupus Nephritis !

Classe III: Glomerulonefrite proliferativa focale e segmentale


MO: Aree di proliferazione glomerulare a carico delle cellule mesangiali ed
endoteliali, con infiltrato infiammatorio, necrosi e sclerosi. E coinvolta una
porzione del glomerulo inferiore al 50%

IF: Depositi immuni diffusi a livello mesangiale e capillare.


ME: Depositi immuni subendoteliali e mesangiali.
Manifestazioni cliniche: Molti pazienti hanno un LES sistemico in fase attiva ed
un interessamento renale da lieve a moderato con ematuria e proteinuria.
Una minoranza mostra un peggioramento della funzione renale e pu
progredire nella quarta classe. !
World Health Organization Classification of Lupus
Nephritis
Classe IV: Glomerulonefrite proliferativa diffusa
MO: Proliferazione glomerulare soprattutto a carico delle cellule endoteliali
determinano una occlusione dello spazio capillare, infiltrato leucocitario,
necrosi, semilune, sclerosi. Depositi ialini sono presenti nelle pareti capillari o
nei vasi. Sono coinvolti diffusamente oltre il 50% dei glomeruli.
IF: Deposti immuni irregolari nel mesangio e nelle pareti dei capillari.

ME: Grandi depositi immuni sottoendoteliali o mesangiali sono presenti;


World Health
occasionalmente Organization
anche depositi Classification
sottoepiteliali of Lupus
e intramembranosi
Manifestazioni cliniche: Ipertensione, edema, alterazioni del sedimento urinario, !
peggioramento della funzione renale, Nephritis
proteinuria nefrosica.
Classe V: Glomerulonefrite membranosa diffusa
MO: Ispessimento diffuso della membrana basale glomerulare senza infiltrato
infiammatorio. Allimpregnazione argentica sono osservabili depositi
sottoepiteliali e spikes. Le lesioni membranose sono a volte associate a
lesioni proliferative focali o diffuse.
IF: Depositi immuni nelle pareti capillari e a livello mesangiale.

ME: Depositi immuni sottoepiteliali e membranosi; i depositi endoteliali si


osservano solo se c anche una componente proliferativa.

Manifestazioni cliniche: Segni clinici e di laboratorio di sindrome nefrosica, in


genere associati a manifestazioni di attivit el LES. !
!

!
World Health Organization Classification of Lupus Nephritis

Classe VI: Glomerulonefrite sclerosante !


Ottico: Sono caratteristiche la sclerosi glomerulare avanzata, fibrosi !
interstiziale, atrofia tubulare, che sono tutte manifestazioni di danno renale
irreversibile. Le aree di proliferazione sono rare o assenti. !

!
Manifestazioni cliniche: Linsufficienza renale invariabilmente presente e
di solito non risponde alla terapia. !

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!
Crioglobulinemia
Le crioglobuline sono immunoglobuline che precipitano alle basse temperature.
La crioglobulinemia pu essere associate con una particolare malattia
(linfoma, malattia autoimmune, malattia infettiva) o pu essere idiopatica ed
allora denominata crioglobulinemia essenziale. In base alla composizione,
si distinguono tre tipi di crioglobulinemia:
! Tipo I, o crioglobulinemia semplice, dovuta ad una Ig monoclonale, di solito
una IgM o una IgG.
! Tipo II e tipo III o crioglobulinemia mista, che contengono un fattore
reumatoide, di solito una IgM, che si complessa con il frammento Fc di Ig
policlonali. A sua volta, il fattore reumatoide pu essere monoclonale (tipo II),
o policlonale (tipo III).
Fisiopatologia: E una malattia da immunocomplessi. I pazienti hanno depositi
intravscolari di Ig e bassi livelli di complemento. La crioprecipitazione in vivo
determina trombosi delle piccole arterie e dei capillari alle estremit
(gangrena) ed a livello glomerulare (IRA), nonch iperviscosit.
Prevalenza: la prevalenza della crioglobulinemia mista esenziale di circa 1
caso su 100.000. Le frequenze relative sono: tipo I 25%, tipo II 25%, e tipo III
50%. Una positivit per la crioglobulinemia (50-60% dei casi) si ritrova nei
soggetti con infezione da HCV. Storia clinica
Le manifestazioni pi tipiche dei tipi II e III sono artralgie ed artriti
delle interfalangee prossimali, metacarpofalangee, ginocchia ed anche;
malattia renale e lesioni vascolari purpuriche. In particolare il tipo II si
associa con elevatissima frequenza ad interessamento renale ed
infezione da HCV. La varie manifestazioni hanno la seguente frequenza:
! Porpora, necrosi distale, orticaria, ulcerazioni, debolezza: 55-100%
! Manifestazioni articolari: 35-72%
! Coinvolgimento renale: 8-57%
! Fenomeno di Raynaud: 28-50%
! Parestesie e neuropatia periferica: 10-30%
! Dolore addominale: 2-22%
! Acrocianosi: 9%
! Emorragie: 7%
! Trombosi arteriolare: 1%
La prognosi dipende in genere dalla malattia di base, ma peggiora
quando c interessamento renale, con una sopravvivenza che varia dal
60% a 5 anni al 30% a 7 anni. La morbilit della crioglobulinemia
legata soprattutto alle trombosi arteriosa ed alla malattia renale.
!

!
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Sindrome di Fanconi: E caratterizzata da una disfunzione del tubulo


prossimale che determina perdita di fosfato, glucosio, amminoacidi e
bicarbonati dai tubuli. Pu trattarsi di una malattia ereditaria (nei bambini) o
acquisita, ed allora associata con una paraproteinemia.

Malattia da depositi di catene leggere: E una malattia sistemica causata da


uniperproduzione e deposizione extracellulare di catene leggere monoclonali.
I depositi sono granulari e non formano fibrille e sono negative alla colorazione
per il rosso Congo. I depositi sono dovuti alla regione costante delle
immunoglobuline, e determinano un rilascio di TGF-beta da parte delle cellule
mesangiali che detrmina rilascio di proteine della matrice extracellulare e
sclerosi renale.

Rene da mieloma: oltre il 50% dei pazienti affetti da mieloma muore di


insufficienza renale, ma solo una parte di essi ha effettivamente un rene da
mieloma, nel quale cilindri di proteine ostruiscono i tubuli distali ed i dotti
collettori, la proteina di Bence-Jones svolge unazione tossica sulle cellule
tubulari, si riduce il flusso renale ed il filtrato glomerulare, lipercalcemia e la
disidratazione peggiorano il danno renale. !
!
Amiloidosi
Lamiloide non una singola sostanza ma una famiglia di glicoproteine
complesse a composizione variabile, con una comune configurazione a
beta-pleated sheet alla diffrazione a raggi x e una birifrangenza
verde se colorata con Rosso Congo.

Sono stati identificati due tipi principali di amiloide:


Amiloide AA. La componente principale una proteina di 76 amminoacidi
senza nessuna relazione con le immunoglobuline. Questo tipo di amiloidosi
secondaria a malattie sistemiche croniche come lartrite reumatoide, la sifilide,
losteomielite cronica e le febbre familiare del Mediterraneo.
Amiloide AL. Le catene leggere delle immunoglobuline sono il maggior
costituente dellamiloide AL e si trovano nei pazienti con amiloidosi primitiva
o nel mieloma multiplo (6-24%). In una rilevante quota di pazienti con
amiloidosi primitiva si osserva una discrasia plasmacellulare nel midollo,
catene leggere nel siero, e proteinuria di Bence-Jones.
Il meccanismo di formazione dellamiloide rimane sconosciuto. Studi su
modelli animali ed in vitro suggeriscono che nellamiloidosi secondaria, una
cronica stimolazione dei monociti da parte della IL-1 induca il fegato a
produrre una proteina precursore denominata amiloide sierica, che viene poi
degradata dai macrofagi con generazione delle proteine fibrillari caratteristiche
dellamiloide. Sebbene non si conoscano eventi simili per lamiloidosi AL, si
ritiene che anchessa venga generata dai macrofagi.

Storia clinica

I pazienti possono presentarsi con i sintomi della malattia


sotostante e/o con i sintomi della malattia renale associata.
Debolezza e letargia
Persita di peso, anoressia
Dolore osseo, fratture
Neuropatia periferica

Sintomi di IR. Edema, dispnea.


Sintomi della Sindrome di Fanconi si verificano nel 30% dei
pazienti con proteinuria da catene leggere (glicosuria,
aminoaciduria, fosfaturia, lisozimuria, e acidosi tubulare
prossimale).
Assenza di sintomi: Una funzione renale normale si osserva
nel 10-40% dei pazienti.
Sindrome nefrosica: Si verifica nel 30% dei pazienti.
Poliuria e polidipsia
Infezioni ricorrenti !
!
Prognosi
La prognosi legata alla malattia sottostante. Linsufficienza renale pi
frequente nella malattia da catene leggere. Linsufficienza renale acuta si
osserva nell8-30% e linsufficienza renale cronica nel 30-60% dei casi.
Gammopatia monoclonale benigna: solo l1-2% dei pazienti sviluppa IR,
alcuni hanno lieve proteinuria ed ematuria.
Malattia da depositi di catene leggere: La prognosi non buona e la morte
spesso dovuta ad insufficienza cardiaca. La sopravviveza 90% ad 1
anno e 70 % a 5 anni, e la sopravvivenza renale dopo chemioterapia (ie,
with melphalan and prednisone), del 67% e 37% ad 1 e 5 anni
rispettivamente.
Mieloma multiplo: Le infezioni e lIR sono le principali cause di morte. La
prevalenza di IR del 14% nel mieloma ad IgG, 33% ad IgA, 60% ad IgD.
Amiloidosi: La sopravvivenza nei pazienti con amiloidosi AL del 50% a
meno di due anni. Nei pazienti trattati (melphalan e prednisone) la
sopravvivenza del 78% a 5 anni contro il 7% dei non trattati.

Il Rosso Congo sicuramente


considerato la colorazione pi
attendibile a porre diagnosi di Amiloide
glomerulare e vascolare
L'amiloide appare al microscopio ottico
come una sostanza extracellulare
amorfa, eosinofila, PAS negativa o
debolmente positiva.

!
!

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OSTRUZIONE TOSSICI FARMACI CRISTALLI INFEZIONI ISCHEMIA

DANNO
CELLULE
TUBULARI

ESPRESSIONE RILASCIO DI CITOKINE FUNZIONE TRANSIZIONE


ATG HLA PROTEINASI, MOLECOLE PRESENTAZIONE EPITELIO-
DI ADESONE E FATTORI ATG MESENCHIMALE
DI CRESCITA

NECROSI RECLUTAMENTO RECLUTAMENTO


APOPTOSI ED ATTIVAZIONE ED ATTIVAZIONE
LINFOCITI T E FIBROBLASTI
MACROFAGI

ATROFIA INFILTRATI FIBROSI


TUBULARE INTERSTIZIALI INTERSTIZIALE

DISFUNZIONE PERFUSIONE
TUBULARE CAPILLARE
!
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,%&)!%00+*+#')!7/(4+*1/%*)3!'0-.(/'")&%$/(,1%",(9))
!

ATROFIA
CRISTALLI, FLOGOSI, FIBROSI TUBULARE
(TCP, BRANCA SPESSA
CILINDRI, ECC INTERSTIZIALE ASCENDENNTE HENLE

AB AB NUMERO E
RIASSORBIMENTO
INTRINSECO ESTRINSECO CALIBRO
CAPILLARI DI ACQUA E SODIO

OSTRUZIONE RESISTENZE CARICO DISTALE DI


TUBULARE VASCOLARI ACQUA E SOLUTI

VASI AFFERENTI VASI EFFERENTI


AI GLOMERULI DAI GLOMERULI
FEEDBACK
TUBULO
GLOMERULARE

PRESSIONE ISCHEMIA IPERTENSIONE


RILASCIO RENINA
TUBULARE GLOMERULARE GLOMERULARE PRODUZ. ANGIOT II

RELATIVA
VASODILATAZ. ART.
GLOM. EFF.

ATROFIA DANNO FILTRAZIONE


TUBULARE GLOMERULARE GLOMERULARE
!
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%1'()441#)3!-(4+!)/!EaO3!/%!7*%#1/(4%'(&)!5)!t+7+#+*3!/%!4)-*($(/)%#7)()'+3!/%!
&)#5*(4+!5)!Opy7*+#3!4%!%#-.+!4%/%'')+!(#-(+4%'(/(7)-.+3!-(4+!)/!4)+/(4%!41/')$/(!+!
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$1N!+&&+*+!/%!&+71+#'+G!
CAUSE

IDIOPATICA
IDIOPATICA ENDEMICA (nefropatia dei Balcani)
EREDITARIE: nefronoftisi, malattia cistica midollare, nefropatia iperuricemica
familiare giovanile, ADPKD, ARPKD
INFEZIONI: pielonefrite cronica, pielonefrite xantogranulomatosa,
malacoplachia, TBC.
FARMACI E TOSSICI: analgesici, acido aristolochico, litio, ciclosporina,
tacrolimus, indinavir, cisplatino.
METALLI PESANTI: piombo, cadmio, arsenico, mercurio, oro, uranio.
RADIAZIONI, ONDE DURTO
ALTERAZIONI METABOLICHE: iperuricemia, ipopotassiemia, ipercalcemia,
iperossaluria, cistinosi.
MALATTIE AUTOIMMUNI: LES, sindrome di Syogren, sarcoidosi, sindrome di
Wegener ed altre vasculiti.
OSTRUZIONE CRONICA, REFLUSSO VESCICO-URETERALE
MALATTIE EMATOLOGICHE: mieloma, leucemie, linfomi, anemia falciforme,
emoglobinuria parossistica notturna
MALATTIE VASCOLARI: malattia renale aterosclerotica
RIGETTO CRONICO DI TRAPIANTO RENALE
SECONDARIA A MALATTIE GLOMERULARI PROGRESSIVE:
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CORTICALE - normale
MIDOLLARE ESTERNA normale

PAPILLA E MIDOLLARE INTERNA alterazioni focali: sclerosi


Stage I capillare, necrosi focali cellule interstiziali, branche sottili Henle,
vasa recta

CORTICALE - normale
MIDOLLARE ESTERNA comparsa alterazioni focali

PAPILLA E MIDOLLARE INTERNA necrosi ed atrofia progressive

Stage II
Atrofia in corrispondenza della papilla necrotica
CORTICALE
Ipertrofia (raggi midollari risparmiati)

PAPILLA atrofia e necrosi totale

Stage III
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CRITERI DIAGNOSTICI DI NEFROPATIA DA ANALGESICI IN
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PAZIENTI CON INSUFFICIENZA RENALE CRONICA (TC DIRETTA)
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Dimensioni diminuite = A+ B < 103 mm (M) o < 96 mm (F).


Contorni bozzuti = almeno 3 incisure
!
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industriali, proiettili ritenuti, batterie, whiskey di contrabbando, additivi per vini e farmaci,
ecc.

Categorie a rischio: Lavoratori nella produzione di vernici e ceramiche, costruzione di auto,


demolizione di edifici, produzione di carburanti, impiegati in fonderie, in miniere, in
stamperie, in poligoni di tiro, bambini (picacismo)!

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!
NEFROPATIA CRONICA DA PIOMBO
_)%7#(&)!!
DIAGNOSI
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ANAMNESI OCCUPAZIONALE
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'+&'!5)!-.+/%2)(#+!-(#!a_VMG!
ASSOCIAZIONE GOTTA-INSUFFICIENZA RENALE

Riflettono usualmente ESPOSIZIONE RECENTE


LIVELLI EMATICI
DI PIOMBO
> 80 mcg/dl (adulto) Suggerito
> 40 mcg/dl (bambino) sovraccarico di
> 10 mcg/dl persistentemente
Pb

1.0 g X 2 im (intervallo 12 ore)


TEST DI 0.5 g x 2 ev (intervallo 12 ore) in 250 cc SG 5 %
CHELAZIONE
CON (Na-Ca)EDTA Pburia > 650 mg nelle 24 ore successive (creat < 1.5 mg/dl)
Pburia > 650 mg nelle 72 ore successive (creat > 1.5 mg/dl)
!
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NEFROPATIA CRONICA DA LITIO
!
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)

DANNO TUBULO INTERSTIZIALE


FIBROSI INTERSTIZIALE CRONICA focale relativamente acellulare
ATROFIA E DILATAZIONE TUBULARE
MICROCISTI (origine da tubuli distali e dotti collettori) corticali e midollari di
diametro 1-2 mm

DANNO GLOMERULARE
Usuale relativo RISPARMIO dei glomeruli
Casi di GLOMERULONEFRITE A LESIONI MINIME
In pazienti con insufficienza renale (= tardivamente) frequente riscontro di
GLOMERULOSCLEROSI GLOBALE o GLOMERULOSCLEROSI FOCALE
SEGMENTARIA con glomerulomegalia
) )
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NEFROPATIA CRONICA DA LITIO (RM)
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!
T2 RARE !
T2 (rapid acquisition relaxation enhancemen)

!
Numerose microcisti rotondeggianti del diametro di 1-2
mm in tutte le aree della corticale e della midollare
renale.

Farres MT, Radiology 2003, Nov: 570


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PATOGENESI
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CyA (calcio antagonisti dididropiridinici)
- Evitare deplezione sodica?

!
!
!
!
NEFROPATIA
=(+,$6"#'")3")"-'3$)1,'-$) DA ACIDO URICOBobadilla NA, AJP Renal Physiol 2007; 29
)
PURINE (acidi nucleici)

ACIDO URICO

Ominidi e
Primati Primati
superiori inferiori

URICASI

- FILTRAZIONE GLOMERULARE (100 %) ALLANTOINA

-RIASSORBIMENTO TCP (90 %)


# riassorbimento presecretorio
# secrezione
# riassorbimento postsecretorio
)
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!
< Lo sviluppo di nefropatia gottosa non comune nella stragrande maggioranza di
pz con gotta.

< Le lesioni istologiche pi frequenti documentabili in pz iperuricemici con


insufficienza renale sono a carico dei vasi (nefrosclerosi).

< improbabile che iperuricemia e gotta da sole conducano a significativa


insufficienza renale.

< Studi epidemiologici non sono riusciti ad identificare lacido urico come fattore di
rischio indipendente di insufficienza renale.

< Lo sviluppo di insufficienza renale in pazienti iperuricemici (asintomatici e


gottosi) usualmente attribuibile allassociata ipertensione arteriosa.
)
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'6(,#(*0'$*(L'*3'6(*3(*#(C!&%*+66+!$()!/B)$+*'+#&)(#+!*)&1/'%#'+!%!-%1&%*+!7*%#!$%*'+!
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&$)+7%*+!)/!/+7%4+!'*%!)$+*1*)-+4)%!-*(#)-%!+!#+0*($%')%8!
!
IPERURICEMIA CRONICA

AUMENTATO INGRESSO DI ACIDO URICO IN


CELLULE ENDOTELIALI, MM LISCE VASCOLARI

DISFUNZIONE ENDOT. ATTIVAZIONE SISTEMA


RILASCIO NO RENINA-ANGIOTENSINA

VASOCOSTRIZIONE
(SISTEMICA E RENALE)

ROS ED ALTRI PROLIFERAZIONE


MEDIATORI IPERTENSIONE CELLULE MM
INFIAMMATORI (insensibile al sale) LISCE VASCOLARI

ARTERIOLOPATIA AFFERENTE
FIBROSI INTERSTIZIALE

IPERTENSIONE
(sensibile al sale)

INSUFFICIENZA RENALE !
!
V+*%$)%!
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NEFROPATIA CRONICA
< R*#$00'-"2'$*()3")7'#"/'*")V) IPERCALCEMICA
)

IPERCALCEMIA CRONICA

filtrazione glomerulare

VASOCOSTRIZIONE CONCENTRAZIONE OSTRUZIONE


(sistemica e renale) INTRATUBULARE DI CALCIO INTRATUBULARE
(midollare)

DEPOSIZIONE INTERSTIZIALE
DI CALCIO

INFILTRAZIONE CELLULARE
MONONUCLEATA

ISCHEMIA/IPOSSIA DEGENERAZIONE/NECROSI CELLULE


(preval. midollare) TUBULARI (midollare)
)
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NASCITA DELLA NEFROCALCINOSI
(microscopica)
TUBULI CONTENENTI
CRISTALLI CON
EPITELIO NORMALE GRANULOMA

TUBULI CON CRISTALLI TUBULI CON CRISTALLI TUBULI CON CRISTALLI


ADERENTI A CELLULE SORMONTATI DA DIREZIONATI
RIGENERANTI APPIATTITE EPITELIO TUBULARE NELLINTERSTIZIO
!
! NEFROCALCINOSI MIDOLLARE Vervaet BA, Kid Int 2009; 75: 41
`%*%4+#'+!/%!#+0*(-%/-)#(&)!)#'+*+&&%!/%!-$,#'-"%(3!+!7+#+*%/4+#'+!&)!'*%''%!5)!-%&)!
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!
CAUSE
-Iperparatiroidismo primitivo (1 causa)
-Acidosi tubulare distale (2 causa)
-Rene a spugna midollare (depositi in dotti collettori terminali dilatati)
-Necrosi papillare
-TBC renale
-Immobilizzazione prolungata (specialmente in et pediatrica)
-Senilit, menopausa, steroidi
-Sindrome da latte ed alcali
-Ipervitaminosi D
-Rachitismi vit D resistenti (trattati con vit D)
-Sarcoidosi
-Iperossaluria primitiva
-Prematurit
!
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Stenosi monolaterale dellarteria renale

Dalla parte del rene stenotico Dalla parte del rene sano
Perfusione renale e GFR Pressione di perfusione renale

RAS, Renina
Angiotensina II GFR Aumentata
Aldosterone RAS soppresso
escrezione di Na

normali livelli PRA


Ipertensione angiotensina II dipendente vena periferica

Blocco del RAS


Ridotta pressione arteriosa
Lateralizzazione dopo test diagnostici
Il filtrato glomerulare si riduce nel rene stenotico
19
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Stenosi dellarteria renale bilaterale o in monorene

Perfusione renale e GFR


attivazione sistema
Renina - Angiotensina
Aldosterone

Riduzione dellescrezione di Na
Edema
polmonare
acuto Espansione di volume

Aumento della pressione arteriosa

Blocco del RAS


Riduzione anche marcata del filtrato glomerulare
Ridotta pressione arteriosa solo dopo aver ottenuto una deplezione di volume
!
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Evoluzione
Evoluzione
Evoluzione della
della
della nefropatia
nefropatia
nefropatia ischemica:
ischemica:
ischemica:
A)
A) Aterosclerosi
A) Aterosclerosi
Aterosclerosi aortica
aortica
aortica digrado
di di
gradogrado lieve;
lieve;
lieve; reni reni
reni
con con struttura e funzione
strutturae efunzione
con struttura funzione conservate
conservate
conservate
B) Aterosclerosi progressiva: stenosi arteria
B)
B) Aterosclerosi progressiva:
Aterosclerosi progressiva:
renale monolaterale, stenosi
stenosi
con ipotrofia
arteriaarteria
del rene,
renale monolaterale,
renale monolaterale, concon
ipotrofia del rene,
ipotrofia del rene,
funzione globale conservata per laumento
funzione globale conservata per laumento
funzione
del GRF globale
nel reneconservata
controlateraleper laumento
del GRF
C) nel rene progressione
Lulteriore controlaterale delle lesioni ate-
del GRF nel rene
C) Lulteriore controlaterale
progressione delle lesioni ate-
rosclerotiche compromettono entrambi i
C) Lulteriore
rosclerotiche progressione
compromettono
reni, con evidenti
delle
entrambi
danni strutturali
lesioni
i
e deficit
ate-
rosclerotiche
reni,funzionale.
con evidenti compromettono
danni strutturali entrambi
e deficit23 i
! reni, con evidenti danni strutturali e23deficit
funzionale.
funzionale. 23
!

H*+&+#'%2)(#+!-/)#)-%!

< R*01++'-'(*2"),(*"%()"-1#")3")S;4LR)()0",#"*')
H+*-.[!)4$*(,,)&%4+#'+!,)+#+!%!4%#-%*+!)/!4+--%#)&4(!-.+!&'%,%!4%#'+#+#5(!
/%!01#2)(#+!*+#%/+3!-)(?!)/!&)&'+4%!*+#)#%<%#7)('+#&)#%8!
< R*01++'-'(*2"),(*"%()6,$&,(00'7")
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*+&)&'+#'+!%//%!'+*%$)%3!(!)#!1#!$%2)+#'+!-(#!%'+*(&-/+*(&)!$(/)5)&'*+''1%/+8!
< 46'0$3')3')(3(/")6$%/$*",()"-1#$),'-$,,(*#'))
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!

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$%*+#-.)4%/)!*+#%/)8!!
Stenosi dellarteria renale, ipertensione ed IRC

La maggioranza dei pazienti ipertesi con stenosi dellarteria renale


L1+&'%!)44%7)#+!-)!&$)+7%!-(4+!)$+*'+#&)(#+3!&'+#(&)!5+//B%*'+*)%!*+#%/+!+5!)#&100)-)+#2%!
*+#%/+!-*(#)-%!&)%#(!'*+!-(#5)2)(#)!-.+!$(&&(#(!+&)&'+*+!%1'(#(4%4+#'+3!($$1*+!
ha una-(46)#%*&)!)#!,%*)(!4(5(8!_%!#('%*+3!-(41#:1+3!-.+!/%!4%77)(*!$%*'+!5+)!$%2)+#')!-(#!
ipertensione essenziale, come dimostrato dal fatto che
lipertensione di solito persiste nonostante la rivascolarizzazione
&'+#(&)!5+//B%*'+*)%!*+#%/+!.%!1#B)$+*'+#&)(#+!+&&+#2)%/+3!'%#'B?!-.+!4(/'(!&$+&&(!/%!
*),%&-(/%*)22%2)(#+!#(#!5+'+*4)#%!)/!*)+#'*(!5+)!,%/(*)!$*+&&(*)!#+//%!#(*4%8!!

S66,$--'$)V'"&*$0#'-$)
Esami finalizzati alla visualizzazione delle arterie renali
>9 <#"C'%',()%5(0'0#(*2")3')1*")0#(*$0')

EcocolorDoppler: Mostra le arterie renali e misura la velocit del flusso come


mezzo per valutare la severit della stenosi. E economica e largamente
disponibile, ma molto legata allesperienza delloperatore, alla presenza di
obesit o di aria nellintestino; meno utile dellangiografia per la diagnosi di
displasia fibromuscolare e di anomalie della arterie renali accessorie. Associata
allecografia, da informazioni sul parenchima renale. E il test di screening per
la diagnosi di stenosi dellarteria renale
Angio RMN: Mostra le arterie renali e laorta perirenale Il gadolinio non
nefrotossico; utile nei pazienti con IR; d immagini eccellenti. E costosa:
meno utile dellangiografia invasiva per la diagnosi di displasia fibromuscolare
e di anomalie della arterie renali accessorie.
Angio TC: Mostra le arterie renali e laorta perirenale. Gli stent non sono causa
di artefatti. I grandi volumi di mdc richiesti sono potenzialmente nefrotossici.
Angiografia: langiografia (con o senza sottrazione digitale) il golden
standard per la diagnosi di stenosi dellarteria renale. Lesame viene peraltro in
genere eseguito per effettuare langioplastica o valutare in maniera ottimale
lanatomia vascolare a scopo chirurgico 29
)
A9 <#"C'%',()'%),"66$,#$)#,")'6(,#(*0'$*()()0#(*$0')
9,,+*(3!/B)$+*'+#&)(#+!?!-%1&%'%!5%//%!&'+#(&)v!O)!'*%''%!5)!1#B)$+*'+#&)(#+!
+&&+#2)%/+!)#!1#!$%2)+#'+!-(#!&'+#(&)!5+//B%*'+*)%!*+#%/+v!O)!'*%''%!5)!
1#B)$+*'+#&)(#+!#+0*($%*+#-.)4%/+!)#!1#!$%2)+#'+!-.+3!)#-)5+#'%/4+#'+3!.%!
Studio del sistema renina-angiotensina
%#-.+!1#%!&'+#(&)!5+//B%*'+*)%!*+#%/+v!!

H+*!,%/1'%*+!)/!*%$$(*'(!'*%!)$+*'+#&)(#+!+!&'+#(&)3!&)!5+,+!&'15)%*+!)/!&)&'+4%!*+#)#%<
Serve per valutare il rapporto fra stenosi ed ipertensione
%#7)('+#&)#%8!

Misura della PRA dopo test al captopril


Il farmaco determina una riduzione della caduta della pressione
arteriosa distale alla stenosi ed aumenta il rilascio di renina da
parte del rene stenotico, ma ha un basso valore predittivo nei
confronti dellipertensione renovascolare, perch i risultati
vengono influenzati da altre condizioni. Il test ha di fatto un
valore puramente storico (il test provocativo di primo impiego
oggi la scintigrafia renale).

Angioscintigrafia con test provocativo al captopril


Pu essere effettuata con 99mTc-MAG3, 99mTc-DTPA o 131I-
Hippuran. La caduta della pressione di perfusione dopo
trattamento con Captopril amplifica le differenze di perfusione
e funzione renale. Un esame negativo esclude lipertensione
renovascolare. Ci sono molte limitazioni nei pazienti con
creatinina>2.0 mg/dl
Misura della PRA nella vena renale: Paragona il rilascio di 30
renina da parte dei due reni; la lateralizzazione
(specialmente se associata a soppressione controlaterale)
con un fattore predittivo del miglioramento della pressione
arteriosa a seguito della rivascolarizzazione; se la
lateralizzazione non c questo non significa che la
rivascolarizzazione non possa risolvere il problema. I risultati
possono comunque essere alterati dai farmaci e da altre
condizioni cliniche

Lateralizzazione = renina nel rene ischemico/renina nel rene


contro-laterale > 1,5
Soppressione controlaterale = renina nel rene controlaterale
renina nella vena cava infrarenale (cio periferica) = 0
!
!
Questi test vanno interpretati con molta prudenza nella maggior parte dei pazienti anziani con
stenosi
! dellarteria renale ed ipertensione, dal momento che lipertensione non renina-
dipendente ed i risultati non predicono in maniera accurata landamento dellipertensione
! la rivascolarizzazione; inoltre i risultati sono influenzati da molte altre condizioni
dopo 32
!

!
D9 <#"C'%',()'%),"66$,#$)#,")0#(*$0')3(%%5",#(,'"),(*"%()()3"**$)6",(*-.'/"%()
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Studio della funzione renale
'*%''%!)#,+-+!5)!1#%!#+0*($%')%!$%*+#-.)4%/+!-(#!%##+&&%!&'+#(&)!5+//B%*'+*)%!
*+#%/+v!O)!'*%''%!5)!1#%!#+0*($%')%!)$+*'+#&),%v!

Misurazione della creatininemia


Esame delle urine (i pazienti con danno renale
ischemico non hanno alterazioni clinicamente
rilevanti del sedimento urinario quali
proteinuria o microematuria glomerulare)
Determinazione del filtrato glomerulare
Valutazione ecografica delle dimensioni dei
reni
!
! 33

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5)%6+')-%Z8!!

8(,"6'")
Terapia
)

Obiettivi Opzioni

! Controllo dellipertensione ! Medica

! Angioplastica senza
(displasia fibro-muscolare) o
! Salvataggio del rene con (aterosclerosi) stenting

! Trattamento dei disturbi ! Rivascolarizzazione


cardiaci (angor, edema chirurgica
polmonare)

! 37

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Prevalenza singoli stadi


"/!&+-(#5(!$*(6/+4%!)4$(*'%#'+3!&($*%''1''(!5%/!IPPP!)#!$()3!?!:1+//(!5+//%!5)001&)(#+!
&+4$*+!$)F!%4$)%!5+)!$%2)+#')!-(#!4%/%'')%!*+#%/+!-*(#)-%!#+7/)!&'%')!W3!I3!K!+!Q8!"#!"'%/)%!
-)*-%!S!4)/)(#)!5)!$+*&(#+!&(#(!%00+''+!5%!4%/%'')%!*+#%/+!-*(#)-%8!
Prevalenza Stima
Stadio GFR
USA % Italia
Danno renale
1 con GFR > 90 3.3 2.000.000
normale o !
Danno renale
2 con GFR 60-89 3.0 1.800.000
lievemente "
Moderata "
3 GFR
30-59 4.3 2.500.000

4 Severa " GFR 15-29 0.2 100.000


Insufficienza
<15 o
5 renale
dialisi
0.1 4-50.000
terminale !
L1+&'(!?!$*(6/+4%')-(!&($*%''1''(!$+*!1#%!*%7)(#+G!&+!?!,+*(!-.+!-B?!1#!-+*'(!*)&-.)(!5)!
+,(/12)(#+!,+*&(!/BaO`_3!1#!$*(6/+4%!%#-(*%!$)F!)4$(*'%#'+!?!:1+//(!*+/%'),(!
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)!0%''(*)!5)!*)&-.)(!-%*5)(,%&-(/%*)3!$(#+#5(&)!&(&'%#2)%/4+#'+!"%)6,'/$)6$0#$)'*%!)!
0%''(*)!5)!*)&-.)(!4%77)(*)8!"/!*)&-.)(!5)!+,+#'(!-%*5)(,%&-(/%*+!)#!1#!$%2)+#'+!-(#!
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S<WP!,(/'+!:1+//(!5+//%!$($(/%2)(#+!7+#+*%/+8!"/!*)&-.)(!5)!+,+#')!\h!)#!1#!$%2)+#'+!-(#!
)#&100)-)+#2%!*+#%/+!'+*4)#%/+!)#!'+*%$)%!&(&')'1'),%!?!$%*)!%!=P<WIP!,(/'+!:1+//(!5+//%!
$($(/%2)(#+!7+#+*%/+G!:1+&'(!&)7#)0)-%!)#!&(/5(#)!1#!*)&-.)(!5+/!WPR!%##1(8!!

L1+&'(!&$)+7%!-(4+!4%)3!%!0*(#'+!5)!-(&e!'%#'+!$+*&(#+!-.+!&(00*(#(!5)!4%/%'')%!*+#%/+!
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!
X%/%'')%!*+#%/+!-*(#)-%!+!*)&-.)(!-%*5)(,%&-(/%*+!

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4%/%'')%!*+#%/+!-*(#)-%!)#!:1%#'(!'%/+3!$+*!$*)4%!-(&%3!%14+#'%!5)!$+*!&[!)/!*)&-.)(!
-%*5)(,%&-(/%*+!$+*!*%7)(#)!#(#!#('+8!

fattori di rischio CV
"#!&+-(#5(!/1(7(3!/%!4%/%'')%!*+#%/+!-*(#)-%!&)!%&&(-)%!%5!1#%!&+*)+!5)!-(#5)2)(#)!D!
%-)5(&)3!&'%'(!)#0)%44%'(*)(!-*(#)-(3!5)&/)$)5+4)%3!)$+*'+#&)(#+!D!-)%&-1#%!5+//+!:1%/)!i)
specifici o influenzati delluremia
+"##$,()3'),'0-.'$)-",3'$7"0-$%",(9)

! Tipo di malattia renale ! Anemia


! Livello di GFR ! Malnutrizione
! Proteinuria ! Infiammazione cronica (alti livelli
! Attivit del sistema RAA di molecole proinfiammatorie e di
adesione quali Il-6, TNF-!, IFN-",
! Aumento del volume del liquido PCR, ICAM-1, VCAM-1, selectina-E)
extracellulare ! Ipercoagulabilit
! Alterazioni del metabolismo Ca-P ! Stress ossidativo
! Dislipidemia
!bassi livelli di HDL colesterolo
! Alti livelli di omocisteina
!alti livelli di particelle VLDL ! Tossine uremiche
remnants e di IDL ricche di
trigliceridi
!prevalenza di LDL piccole e dense
!aumento dei livelli di Lp(a)

!
KDQOI, modificato da NCPE Adult Treatment Panel III
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&+#2%!)#&100)-)+#2%!*+#%/+3!1#(!5+)!$*)4)!(6)+''),)!5+/!#(&'*(!)#'+*,+#'(!?!:1+//(!5)!
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Progressione della nefropatia

blocco RAA,
riduzione PA

fattori del
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APC HLA Canali del Ca

TCR Ca++

Calmodulina

CNA Calcineurina
Fosfatasi Nucleo

Linfocita T NFAT
Trascrizione citochine
pro-infiamm.,CD40L
Citoplasma

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RC 6(0$#'%L%.%'O)'"#)@(&#'(",),)"%-,A,&',)
Z(5()1#)1%"+)23)D3+2'(=).),#)5(&1%'%()2%&+)D3#)&(&8)
)
SC Q(0%+.%#&H#)@%),'O)'"#)@(&#'(",),)"%-,A,&',)
L00+"(;)'+&'%#7()&+%),%7%'%)1+,)$(22%G%,+)1%)&(&)#22+:&#"+)#1)3&)"#:#66(),/(":#&()
$"+,+0#'()1#)3&#)$+"2(&#)#&6%#&#;)+)0%5+0+"2#8)S+"5<%#7()D3%&1%)1%)4("&%"+)#%)
$#6%+&'%)1#)'"#$%#&'#"+)3&)"+&+)5(&)3&#)$"+237%G%,+)43&6%(&+)"+&#,+)%&),%&+#)5(&)
D3+,,#)#''+2#)$+"),/+'I)1+,)$#6%+&'+8)
)
VC !,0$()@%)#'',*#)
L00+"(;)2%)'+&'#)1%)1#"+),#)$"+5+1+&6#)#%)$#6%+&'%)5<+)2%)'"(0#&()1#)$%F)'+7$()%&)
,%2'#)1/#''+2#8)E3+2'()&(&)2+7$"+).)$(22%G%,+;)2($"#''3''()%&)"+,#6%(&+)#,,+)$"%7#)
13+)"+:(,+)5<+)#GG%#7()5%'#'(8)

S(7+)0#,3'%#7(),#)-(0$#'%L%.%'OT)-&)$#"'+)+"#):%I)0+&3'()43("%)$"+5+1+&'+7+&'+8)
N&6%'3''(;).)&+5+22#"%#),#)5(7$#'%G%,%'I)1+:,%)#&'%:+&%)+"%'"(5%'#"%;)2+5(&1()D3+2'+)"+:(,+=)

-&)"+#,'I;)0%)2(&()3&)5+"'()&37+"()1%)
5+&'"%)5<+)<#&&()#5D3%2%'()3&#)5+"'#)
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%&5(7$#'%G%,+C)%)$"('(5(,,%)2%)G#2#&()
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'+"#$%#)%773&(2($$"+22%0#)$%F)
#::"+22%0#)+)#,,#)$,#27#4+"+2%)#,,()
25($()1%)#,,(&'#&#"+)1#,)$,#27#),+)
%773&(:,(G3,%&+)#&'%K#&'%:+&%)
+"%'"(5%'#"%)$"(1(''+)1#,)$#6%+&'+8)-&)
,%&+#)1%)$"%&5%$%(;)5(73&D3+;),#)
5(7$#'%G%,%'I)N[b).)&+5+22#"%#8))

)
)

)
SCORE USED
) FOR THE SELECTION OF PATIENTS IN LIST
) FOR CADAVER KIDNEY TRANSPLANT

E3+2'#)
'#G+,,#)%&0+5+)
5%)7(2'"#)%,)
$3&'+::%()5<+)
0%+&+)
#''"%G3%'()#,,+)
0#"%+)
2%'3#6%(&%)1%)
7%27#'5<)
MHN8)Z*N)2'#)
$+")Q$#&+,)
"+#5'%0+)
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3&)$#"#7+'"()
5<+)2%)
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'+2')
2%+"(,(:%5%)
4#''%)23,)2%+"()
1+,)$#6%+&'+)+)
0(,'%)#,,#)
1%7(2'"#6%(&
+)1%)#&'%5("$%)
#&'%K#&'%:+&%)
37#&%C)2%)+2$"%7+)%&)$+"5+&'3#,+;)%&'+2#)5(7+)Q$+"5+&'3#,+)1%)%&1%0%13%)&+,,#)

FASCE DI ETA
$($(,#6%(&+):+&+"#,+)0+"2()%)D3#,%)%,)2%+"()1+,)$#6%+&'+)2#"+GG+)"+#''%0(R8))

Z+")D3#&'()"%:3#"1#)%,)5"%'+"%()1+,,/,'O?)2%)2+:3+)%&):+&+"#,+)D3+2'#)"+:(,#=)

DONATORE RICEVENTE
A 16 30 A1 16 45
B 31 50 B1 42 59
C 51 60 C1 60 66
D 61 70 D1 > 66
E > 70
)
)

)
!+"#$%#)%773&(2($$"+22%0#)

H#)'+"#$%#)%773&(2($$"+22%0#)<#)"%0(,36%(&#'(),#)'"#$%#&'(,(:%#)A+),#)7+1%5%&#)%&)
:+&+"#,+B8)H#)0+"#)"%0(,36%(&+).)2'#'#)"#$$"+2+&'#'#)2%53"#7+&'+)1#,,/%&'"(136%(&+)1+:,%)
%&%G%'("%)1+,,#)5#,5%&+3"%&#;)5(7+),#)-%-.(*$("%&#C)H#)5%5,(2$("%&#).):"#0#'#)1#)3&)
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Tossicit da inibitori della calcineurina


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Reversibili Irreversibili )
Sito dazione Funzionali Strutturali Strutturali )
Arteriola afferente GFR Vasocostrizione Danno endoteliale
)
Danno delle cellule )
Urea
muscolari lisce
Pressione )
sanguigna Obliterazione dei vasi
)
Tubulo prossimale Alterazioni bioumorali Vacuoli Atrofia
K+ )
Mitocondri giganti Fibrosi interstiziale
Mg )
Microcalcificazioni
)
HCO3
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5,%&%5#8))

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"%,%+0()1+,,#)$"+2+&6#)2%73,'#&+#)1+,,+)5(&1%6%(&%)2311+''+8))
IDONEITA DEL DONATORE IDONEITA
ORGANO

RIANIMAZIONE SALA ANATOMIA CENTRO TRAPIANTI


OPERATORIA PATOLOGICA

Rianimatore/ Chirurgo Istopatologo Nefrologo


Coordinatore Chirurgo
Istopatologo
CRT/CIR

Anamnesi
Esame Obiettivo Ispezione
Esami di Laboratorio Palpazione Oncologica Idoneit / Non Idoneit
Esami Strumentali Accertamento Autoptico
V+&:(&()5#'+:("%5#7+&'+)+25,32%)1#)D3#,2%#2%)'%$()1%)$"+,%+0()$#6%+&'%)5(&=)
! Q%,"($(*%'%A%'O)@#)1DUR)()S?)
! Q%,"($(*%'%A%'O)-(&',0$("#&,#)$,")15*3+),@)1:U?)
! [,($.#*%#)0#.%+&#)%&)#''()B'"#&&,)#.->&,)$",-%*,),--,H%(&%I?)
! D&E,H%(&%)*%*',0%-J,)*(*',&>',)@#)0%-"(("+#&%*0%)$,")%)F>#.%)&(&),*%*'(&()
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K S#"5%&(7#)$#$%,,#"+)3"('+,%#,+)
K [#2#,%(7#) CASI PARTICOLARI:
IDONEITA DONATORE (II)
-)'37("%)%&'"#5"#&%5%)2(&()3&)5#$%'(,()$#"'%5(,#"+=)#,53&%)&(&)+25,31(&(),#)1(&#6%(&+;)
#,'"%)"%5<%+1(&()3&#)0#,3'#6%(&+C)%&4%&+;)0+)&+)2(&()1%)$#"'%5(,#"%)5<+)+25,31(&(),#)
Altri Tumori:
1(&#6%(&+)A7+13,,(G,#2'(7#)+1)#2'"(5%'(7#)#&#$,#2'%5(B8))
-,)5#"5%&(7#)$"(2'#'%5().)3&)#,'"()'37("+)5<+)%&)$#"'%5(,#"%)5(&1%6%(&%)$3@)5(&2+&'%"+)
Carcinoma prostatico
5(73&D3+),#)1(&#6%(&+=)
)
DONATORE PSA pos (>50aa)
-PSA totale < 4 ng/ml
-PSA totale / PSA libero < 10 ng/ml / > 25% SI
Esame
Se valoriistopatologico:
superiori:
Adenocarcinoma confinato allinterno della capsula con
-visita urologica
Gleason -eco
<4 intransrettale
tutti i campioni: Rischio Standard
(se possibile)
-esame istopatologico: 1) estemporaneo
Se uno o pi campioni Gleason 4 e/o 2) diffusione
definitivo
extracapsulare: Rischio aumentato ma accettabile
3) immunoistochimica
)
)
)
D&E,H%(&%)

H/%&4+6%(&+)1#)M-V)f)+)U;),#)5(%&4+6%(&+)M[VKMJV)+)'3''+),+)%&4+6%(&%)$+"),+)D3#,%)&(&)
+2%2'#&()$(22%G%,%'I)'+"#$+3'%5<+)0+&:(&()5(&2%1+"#'%)5"%'+"%)1%)+25,32%(&+)1+,)
1(&#'("+8)H/%&4+6%(&+)1#)16U;)%&0+5+;)&(&).)&+5+22#"%#7+&'+)3&)5"%'+"%()1%)
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1%)+25,32%(&+8)

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