23521084-Hematuria-Proteinuria

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HEMATURIAHEMATURIAPROTEINURIAPROTEINURIA

Camelia IONESCUCamelia IONESCUCentrul de Medicina InternaCentrul de Medicina Interna ± ± Nefrologie FundeniNefrologie Fundeni

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HEMATURIAHEMATURIA

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HEMATURIAHEMATURIA

DefinitieDefinitie:: eliminarea prin urina de hematii

ClasificareClasificare:: H. macroscopica (1ml sange / l urina)

H. microscopica ( > 4 hematii / mm3 urina)

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HEMATURIAHEMATURIA

Algoritm de diagnosticAlgoritm de diagnostic

Evidentierea hematuriei

 ± Teste calitative: sumar de urina

 ± Teste cantitative: Addis, Stansfeld -Webb

 ± Teste semicantitative: MO, prezenta hematiilor 

dismorfice (microscopie in contrast de faza)

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HEMATURIAHEMATURIA

Algoritm de diagnosticAlgoritm de diagnostic

Evidentierea hematuriei

 ± Hematurie nonglomerulara

2 posibilitati de hematurie nonglomerulara

1. Cu un singur tip de celula

2. 2 populatii de hematii

- o populatie de celule hemoglobinizate uniform- o populatie de celule cu un continut mai redus

de hemoglobina (secundar lizei in urina acida)

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HEMATURIAHEMATURIA

Algoritm de diagnosticAlgoritm de diagnostic

Evidentierea hematuriei

 ± Hematurie glomerulara

Prezenta hematiilor dismorfice (microscopie

in contrast de faza)

 ± Celule normal hemoglobinizate

 ± Celule cu membrana densa

 ± Acantocite

 ± Celule ³helmet´

* Prezenta a 3 sau mai multe tipuri de celule indica

hematurie glomerulara

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HEMATURIAHEMATURIA

Algoritm de diagnosticAlgoritm de diagnostic

Metode imagistice

 ± Ecografie renala, doppler  ± UIV, CT, RMN

 ± Scintigrama renala

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HEMATURIAHEMATURIA

Algoritm de diagnosticAlgoritm de diagnostic

Evidentierea altor simptome/semne

urinare

 ± Proteinurie

 ± Leucociturie si/sau piurie

Punctie biopsie renala ± De electie in hematuriile glomerulare

 ± Dificil de indicat in hematuria asimptomatica!

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HEMATURIAHEMATURIA

Diagnostic diferentialDiagnostic diferential::

H. reale

 ± H. de cauza renala

 ± H. de cauza extrarenala

Pseudohematurii

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HEMATURIAHEMATURIA

PseudohematuriiPseudohematurii

Hemoglobinurie: ± anemii hemolitice

Mioglobinurie: ± traumatisme cu distructie de masa musculara

Medicamente: ± rifampicina

 ± procainamida

 ± laxative

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HEMATURIAHEMATURIA

PseudohematuriiPseudohematurii

Exces de BD si urobilinogen: ± ictere hemolitice

 ±

hepatite virale

Pigment melanic: ± melanosarcom

Uretroragie: ± traumatisme

 ± infectii (gonoree)

 ± neoplasm

 ± iatrogen (manevre instrumentale)

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HEMATURIAHEMATURIA

Hematuria de cauza extrarenalaHematuria de cauza extrarenala

Diateze hemoragice:

 ± tulburari de coagulare

 ± tratament anticoagulant

Siclemia

Efortul fizic

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HEMATURIAHEMATURIA

Hematurii de cauza renalaHematurii de cauza renala H. izolate:

afectiuni ale tractului urinar si prostatei:

 ± litiaza

 ± tumori benigne si maligne

 ± TBC

 ± traumatisme

 ± medicamente

 ± prostatite

afectiuni ale parenchimului renal:

 ± hematuria benigna recurenta

alte afectiuni

 ± BPADA, alte boli chistice renale

post biopsie renala

 ± in 100% din cazuri; macroscopica in 10% din cazuri

 ± mai frecventa in biopsia grefei vs. rinichi nativ (9,9 vs. 4,8%)

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HEMATURIAHEMATURIA

Hematuria de cauza renalaHematuria de cauza renala

H. asociata cu proteinurie:

 ± glomerulonefrite

 ± nefropatii tubulointerstitiale ± vasculite

H. asociata cu leucociturie si / sau piurie:

 ± Infectii de tract urinar inferior  ± pielonefrite:

specifice (TBC, fungi)

nespecifice

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HEMATURIAHEMATURIA

Glomerulopatii asociate cu episoade de hematuria francaGlomerulopatii asociate cu episoade de hematuria franca

Cronic:

- Nefropatia IgA

- GN mezangiocapilara

- Sd. Alport

- Boala membranelor bazale subtiri

Acut:

- Sd. nefritic acut (GNADPS)

- GN crescentica rapid progresiva

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HEMATURIAHEMATURIA

In nefropatia IgAIn nefropatia IgA

HSP

H. macroscopica

H. microscopica

IRC

Sd. Nefrotic

Hipertensiune

0 10 20 30 40 50 60ani

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HEMATURIAHEMATURIA

In GN poststreptococicaIn GN poststreptococica

hematuriahematuria = semn clinic universal de boala

Asociaza:

- cilindrii hematici

- proteinurie < 2g/24h

- IR (in 75% din cazuri, usoara/moderata)

! In 4% din cazurile de infectii de tract respirator nonstreptococice

poate apare hematurie microscopica.

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HEMATURIAHEMATURIA

In GN poststreptococicaIn GN poststreptococica

GN poststreptococica Nefropatia IgA

Timp mediuinfectie/hematurie 10 zile < 5 zile

Istoric de hematuriemacroscopica recurenta

rar frecvent

Nivel C3 si C4 seric scazut normal

Titrul ASLO crescut normal

Exudaf faringian pozitiv negativDepunere mesangiala IgA absenta prezenta

Hematurie persistenta sauprogresiva, proteinurie siIR post infectie

neobisnuit comun

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HEMATURIAHEMATURIA

In Sd. AlportIn Sd. Alport

Nefropatie ereditara caracterizata prin nefrita progresiva si

pierderea neurosenzoriala a auzului.

hematuria microscopica persistentahematuria microscopica persistenta = cheia de diagnostic

Asociaza:

- proteinurie

- IR

- surditate neurosenzoriala

- tulburari oculare

- trombocitopenia cu trombocite gigante

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PROTEINURIAPROTEINURIA

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PROTEINURIAPROTEINURIA

Proteinurie ± prezenta proteinelor in urina

* < 30 mg/zi ± proteinurie fiziologica (NORMAL)

* > 300 mg/zi ± proteinurie patologica

* 30 ± 300 mg/zi - microalbuminurie (PATOLOGICA)

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MicroalbuminuriaMicroalbuminuria-- semn precoce de afectare renala in HTAE  semn precoce de afectare renala in HTAE --

Afectarea renala in HTAE

Rata excretiei

urinare dealbumina

Rata excretiei

urinare nocturnede albumina

Albumina/creatinina*

Macroalbuminurie

(nefropatie manifesta)

> 300 mg/zi > 200 Qg/min > 25 mg/mmol

Microalbuminurie 30 ± 300 mg/zi 20 ± 200 Qg/min 2,5 ± 25 mg/mmol (B)3,5 ± 25 mg/mmol (F)

Normoalbuminurie < 30 mg/zi < 20 Qg/min < 2,5 mg/mmol (B)

< 3,5 mg/mmol (F)

* Recoltare din prima urina de dimineata

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MicroalbuminuriaMicroalbuminuria

Afectarea renala in HTAE

HTAE

- semn precoce de nefroangioscleroza

- factor de risc cardiovascular

- defineste grad de risc inalt pentru

mortalitatea cardiovasculara precoce

DZ tip 1

- factor de risc in progresiunea bolii renale

- cel mai precoce semn de nefropatie

DZ tip 2

- factor de risc cardiovascular

- defineste grad de risc inalt pentrumortalitatea cardiovasculara precoce

 Bakris GL. J Clin Hypertens 2001; 3 (2): 99-102

Alte situatii in care apare microalbuminurie:

- permeabilitate vasculara anormala

- ateroscleroza

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Screening pentru proteinurie: Urilux S

DETECTIA MICROALBUMINURIEIDETECTIA MICROALBUMINURIEI

Microalbuminuria

Test rapidMicral cu anticorpi

monoclonali anti-albumina umana (IgG)

marcati cu aur coloidal

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PROTEINURIAPROTEINURIA

Determinarea proteinuriei pe dipstick

Eliminare urinara de proteine > 300mg/zi

Eliminare urinara de proteine in urina normala concentrata

pana la un + pe dipstik.

Urina alcalina - raspuns fals pozitiv pentru proteinurie pe

dipstick.

* Determinarea pe dipstick identifica, in principal, albuminuria si nu

detecteaza proteinuria cu lant usor sau proteinele mici din tubii renali

lezati.

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieDeterminare pe dipstick: > 1+

Determinare calitativa prin precipitare cu acid sulfosalicilic ±reactie pozitiva

Determinare cantitativa a eliminarilor urinare/24h - > 300mg

Electroforeza proteinelor urinare

Imunelectroforeza proteinelor urinare

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatie

Determinare cantitativa a eliminarilor urinare/24h - > 300mg

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatie

Determinare cantitativa a eliminarilor urinare/24h - > 300mg

Proteinurie de rang nefrotic > 3,5 g/zi

sustinuta, 4 sapt = SINDROM NEFROTIC

nesustinuta = SINDROM NEFRITIC ACUT

Proteinurie masiva 2 ± 3,5 g/zi

Proteinurie moderata 1 ± 2 g/zi

Proteinurie minima < 1 g/zi

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieDeterminare pe dipstick: > 1+

Determinare calitativa prin precipitare cu acid sulfosalicilic ±reactie pozitiva

Determinare cantitativa a eliminarilor urinare/24h - > 150mg

Electroforeza proteinelor urinare

Imunelectroforeza proteinelor urinare

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieElectroforeza proteinelor urinare

Proteinurie > 3,5 g/zi, sustinuta 4 sapt. = SINDROM NEFROTIC

- Albumina 100% = sindrom nefrotic inalt selectiv

- Albumina > 80% = sindrom nefrotic selectiv

Intotdeauna glomerulara!

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieElectroforeza proteinelor urinare

Proteinurie 2 ± 3,5 g/zi = PROTEINURIE MASIVA

- Albumina > 60% (compozitie similara celei sangvine)

Proteinurie 1 ± 2 g/zi = PROTEINURIE MODERATA

- Predominenta albumina = origine glomerulara

- Predominenta globulinelor = origine tubulara

Glomerulara!

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieElectroforeza proteinelor urinare

Proteinurie < 1 g/zi = PROTEINURIE TUBULARA

- Predominenta globuline

Tubulara!

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieDeterminare pe dipstick: > 1+

Determinare calitativa prin precipitare cu acid sulfosalicilic ±reactie pozitiva

Determinare cantitativa a eliminarilor urinare/24h - > 150mg

Electroforeza proteinelor urinare

Imunelectroforeza proteinelor urinare

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatie

Imunelectroforeza proteinelor urinare

IgMIgM ± ± mielom multiplumielom multiplu

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PROTEINURIAPROTEINURIA

Algoritm de investigatieAlgoritm de investigatieDeterminarea cauzei proteinuriei

Metode imagistice: ecografie

Punctie biopsie renala

in proteinuriile moderate, masive

Alte investigatii specifice: depistarea hematuriei, IR,

imunologice, etc.

* Proteinuriile datorate efortului fizic sau ortostatismului

pot fi excluse prin analiza urinei de dimineata.

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PROTEINURIAPROTEINURIA

Clasificare (1)Clasificare (1)

Provenienta si compozitie:

 ± proteine de origine plasmatica (60%): albumina (40%; 25mg/zi) IgG (5-10%; 1,98mg/zi)

IgA (3%; 0,54mg/zi)

IgM, lanþuri usoare (5%; 3,5mg/zi)

diverse

 ± proteine si glicoproteine provenite din tubii sicaile urinare:

glicoproteina Tamm-Horsfall (30-60mg/zi)

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PROTEINURIAPROTEINURIA

Clasificare (2)Clasificare (2)

Selectivitate

 ± Indice de selectivitate = Cl IgG / Cl alb

 ±Proteinurie ±

selectiva: IS < 10%» semnificã leziune glomerularã

neselectiva: IS > 20%

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PROTEINURIEPROTEINURIE

Clasificare (3)Clasificare (3)

Debit pe 24h P. masiva > 3,5g/zi = sd. nefrotic

P. mare 2-3,5g/zi = glomerulopatie P. moderatã < 2g/zi:

 ± cu predominenta albuminelor:

» nefropatii glomerulare

» nefropatii tubulointerstitiale

 ±cu predominenta globulinelor:

» nefropatii tubulointerstitiale

 ± cu varf de IgM:

» gamapatie monoclonalã

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PROTEINURIAPROTEINURIA

Cauze (1)Cauze (1)

PROTEINURIE NEPATOLOGICA

 ± TRANZITORIE BENIGNA: < 1g/zi, sex M, tânãr 

 ± FUNCTIONALA: < 2g/zi

Factori favorizanti:

 ± hiperlordoza

 ± efort fizic

 ± febra ± expunere la cãldurã

 ± ORTOSTATICA: < 1-2g/zi

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PROTEINURIAPROTEINURIACAUZE (2)CAUZE (2)

PROTEINURIA PATOLOGICA

 ±

PRERENALA: perfuzii cu proteine sau derivate proteice

hemoliza acuta

distructie tisulara severa

sindroame proliferative (MM, LLC, limfoame)

Nu exista afectare glomerulara sau tubulara asociata !

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PROTEINURIAPROTEINURIA

CAUZE (3)CAUZE (3)

PROTEINURIE PATOLOGICA

 ± GLOMERULARA:

Glomerulonefrite primitive:

 ± leziuni minimale

 ± hialinoscleroza focala si segmentala

 ± membranoasa

 ± membranoproliferativa

Glomerulonefrite secundare:

 ± infectioase: streptococ, VHB, VHC

 ± boli sistemice: LES, Henoch-Schonlein

 ± neoplazii: b. Hodgkin, leucemii, carcinoame

 ± diabet zaharat

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PROTEINURIAPROTEINURIA

CAUZE (4)CAUZE (4)

PROTEINURIE PATOLOGICA

 ± TUBULARA:

Propriu - zisa:

 ± congenitala: sd. Fanconi, sd. Bartter 

 ± dobandita:

» substante chimice: Cd, Hg, As, organomercuriale

» medicamente: aminoglicozide, AINS, fenitoin,penicilamina

» boli sistemice: LES, Sjogreen, sclerodermie» infectii: pielonefrita cronicã

» nefropatia endemicã balcanicã

Secretorie: pielonefrite

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PROTEINURIAPROTEINURIA

CAUZE (5)CAUZE (5) PROTEINURIE PATOLOGICA

 ± PRIN PIERDERI URINARE DE PROTEINE CONSECUTIV

DISTRUCTIEI DE TESUTURI: Histuria:

 ± abces renal

 ± infarct renal

 ± necrozã papilarã

Chiluria: ± sarcina

 ± traumatism renal

 ± cancer renal

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinurii nefrotice

La copil: GN cu leziuni minimale (sd. nefrotic pur)

La tanar: GSFS primitiva (sd. nefrotic impur)

La adult: GN membranoasa (sd. nefrotic impur)

La varstnic: Nefroangiscleroza

Sd. nefrotic asociat cu hipotensiune = amiloidoza renala

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinurii non-nefrotice

Sd. nefritic acut: GN poststreptococica

Proteinurii moderate:

- GN mesangiocapilara

- GN mesangiala

- GSFS primitiva, secundara

- glomeruloscleroza difuza

- GN rapid progresive

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinuria in GN cu leziuni minimale

Cauza a > 80% din sd. nefrotice ale copilului Nu asociaza:

hematurie

IR hipertensiune arteriala

Prezenta hematuriei, HTA sau IR indica afectare

concomitenta mesangiala sau GSFS

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinuria in nefropatia IgA

Poate fi prezenta Sd. Nefrotic in < 10% din cazuri

Este neobisnuita prezenta proteinuriei fara hematurie

microscopica

Factor de prognostic negativ

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinuria in GN membranoasa

Cauza a 30 ± 40% din sd. nefrotice ale adultului Asociaza:

hematurie

IR hipertensiune arteriala

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PROTEINURIAPROTEINURIA

in diverse glomerulopatiiin diverse glomerulopatiiProteinuria in nefropatia diabetica

De la microalbuminurie pana la proteinurie de rang nefrotic Microalbuminuria = prima manifestare a nefropatiei

diabetice

Aparitia microalbuminuriei in DZ tip 1 sau 2 indica

tratament cu blocant al SRAA, independent de valorile TA.

(Ghidul ESH/ESC privind managementul HTA ± 2003)

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Prezentare caz

LM, 22 ani

Motivele prezentarii

 ± 

Edeme ±  HTA

Hematurie

Proteinurie

Punctie biopsie renala

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PBR ± IF (Anti IgG)

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PBR ± IF (Anti C3)

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PBR ± MO (HE)

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Prezentare caz

PBR ± MO (HE)

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Prezentare caz

PBR ± MO (HE)

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Prezentare caz

PBR ± MO (HE)

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