functie renala proteinurie modul studenti
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Examenul paraclinic in nefrologie (cont)
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Indicatiile punctiei-biopsie renale
sdr. nefrotic al adultului
IRA de origine glomerulara (GNRP)
IRA cauzata aparent de necroza tubulara acuta, fara evolutie favorabila dupa 3 saptamini
orice disfunctie renala fara etiologie evidenta la pacient cu rinichi de dimensiuni normale
anomalii urinare asimptomatice persistente
boli sistemice cu afectare renala (LES, amiloidoza, MM)
transplantul renal
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Contraindicatiile punctiei-biopsie renale
disfunctie renala veche, documentata,
mai ales daca rinichii sunt de dimensiuni
mici
rinichi unic morfologic/functional
diateza hemoragica necontrolata
HTA severa necontrolata
infectie urinara
lipsa de complianta a pacientului
orice boala renala la care nu se asteapta
beneficii terapeutice din partea
examenului anatomopatologic
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Punctia-biopsie renala - incidente
durere locala, hematurie macroscopica
tranzitorie, hematom mic - frecvente si
minore
singerare masiva - necesitind transfuzii de
singe, embolizarea arterei singerinde sau
nefrectomie de necesitate <2%
mortalitate = 0.02%, comparabila cu
biopsia hepatica si angiografia
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Evaluarea homeostaziei electrolitice si
AB
Seric: Na 135-145 mmol/l Ca 9-10 mg/dl
K 3,5-5 mmol/l P 3-4,5 mg/dl
Cl =97-103 mmol/l
RA 24-27 mmol/l
Gaura anionica [NA+] - [Cl-] +[HCO-]
N =8-16 mmol/l
gaura anionica > 16 acidoza metabolica cu gaura anionica (intoxicatie?)
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Electrolitii urinari
Na urinar 50-220 mmol/24h
alimentar, pierderi intestinale, sdr.
nefrotic, IRC avansata, IRA (primele
stadii), SN, CH, ICC, sdr. Cushing, sdr.
Conn
alimentar, IRA (poliurie), NTI,
tubulopatii, cetoacidoza
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Electrolitii urinari
K urinar 30-100 mmol/24h
pierderi intestinale, IRC avansata, IRA
(primele stadii), boala Addison
IRA poliurica, tubulopatii (acidoza
tubulara), hiperaldosteronism, sdr.
Cushing, DZ, diuretice, trat. cu
corticosteroizi
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Fractional Excretion of Na (FENa)
FENa: [ urine Na/serum Na] x 100 %
[urine creatinine/serum creatinine]
Diagnosticul diferential al IRA prerenale versus IRA constituita (< 1% versus > 2%)
Indicii renali - vezi si cursul despre IRA
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Investigatii imunologice
ASLO, ac anticorpi anti-stafilolizina
C3 (N>55,60, 90 mg/dl) - calea alterna
C4 (N>15 mgl/dl) - calea clasica
anticorpi antinucleari totali (AAN)
anticorpi antinucleari specifici (anti-ADN dublu
catenari, anti-Sm, anti-Ro, anti-La, anti-
topoizomeraza I etc)
anticorpii c-ANCA si p-ANCA
anticorpi anti-MBG
crioglobuline
AgHBs, aa anti-HCV, VDRL, teste HIV etc
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Anticorpii ANCA
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Evaluarea proteinuriei
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Proteinuria - generalitati
Exista 4 categorii de proteinurii patologice:
glomerulara,
tubulara,
de supraîncarcare,
benigne.
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Proteinuria - tipuri si mecanisme
Proteinuria glomerulara permeabilitate glomerulara crescuta pentru proteine.
Selectiva: predominant pe seama albuminelor. • o Mecanism: alterarea incarcaturii electrice
negative a endoteliului MB glomerulare albuminurie prin lipsa respingerii electrice a albuminelor incarcate electronegativ.
• o Exemplu: nefropatia glomerulara cu leziuni minime
Neselectiva: toate clasele de proteine• o Mecanism: deteriorari severe ale barierei
de filtrare glomerulara• o Exemple: diverse forme de
glomerulonefrite, nefropatia diabetica
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Proteinuria - tipuri si mecanisme
Proteinuria tubulara scaderea reabsorbtiei tubulare a
proteinelor continute în filtratul glomerular.
Exemplu: nefropatii tubulo-interstitiale
Proteinuria de supraincarcare productie si eliberare
crescute de proteine cu Gm joasa (anormale) si scaderea
capacitatii de reabsorbtie a acestor proteine filtrate.
Exemplu: lanturi usoare de Ig (crescute în gamopatiile
monoclonale)
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Proteinuria - tipuri si mecanisme
Proteinuria benigna (functionala) include
proteinuriile „banale”, aparute in absenta unei
boli renale, prin exces de filtrare tranzitor si
posibila scaderea a reabsorbtiei tubulare de
proteine.
PU de efort PU ortostatica repetarea determinarilor!
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Tipuri de proteinurie
electroforeza proteinelor urinare -
proteinurie de tip glomerular/tubular/mixt?
Proteinurie de tip “pur glomerular” -
Glomerulopatie cu leziuni minime
Proteinurie de tip tubular/mixt - sugestie
asupra etiologiei/gravitatii afectarii tubulo-
interstitiale
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Proteinuria
N = absenta/nedozabila cu mijloacele
uzuale (i.e. <0,15 g/24 ore)
PU patologica - PU (0,15) 0,3 g/ ore la determinari repetate
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Proteinuria
Proteinuria semicantitativa determinata prin metoda dipstick se cuantifica astfel:
Urme = 10 - 30 mg/dl1+ = 30 mg/dl2+ = 100mg/dl3+ = 500mg/dl4+ > 2000mg/dl- la indemina oricarui medic si obligatorie
la orice pacient internat/ odata pe an la pacientii “sanatosi”, ca screening!
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Proteinuria (cantitativa)
PU redusa = 0,15 -1 g/24h
PU moderata = 1-3 g/24h
PU severa >3 g/24h
PU de rang nefrotic >3,5 g/24 ore
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Proteinuria cantitativa
atentie la unitatile de masura!
Proteinurie 0,9 g/litru
D= 200 ml/24h, PU = 0,18 g/24 ore
(minima!)
D =4000 ml/24h,PU = 3,6 g/24h (nefrotica!)
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Semnificatia clinica a proteinuriei
Cu cit PU mai severa (constant), cu atit
riscul de progresie spre IRC intr-o boala renala (glomerulonefrita cronica) este mai mare!
riscul de progresie a IRC constituite mai mare!
Proteinurie neresponsiva/putin responsiva la terapia antiproteinurica -evolutie severa
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Proteinuria
N = nedozabila cu mijloacele uzuale (i.e.
<0,15 g/24 ore)
PU minima = 0,15 -1 g/24h
PU moderata 1-3 g/24h
PU severa >3 g/24h
PU de rang nefrotic 3,5 g/24 h/1,73 mp
severitatea PU prezice evolutia bolii
renale!
severitatea PU prezice riscul
cardiovascular!
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Sdr. nefrotic
PU de rang nefrotic 3,5 g/24 h/1,73 mp
+ hipoproteinemie
+ hipoalbuminemie
+ hipercolesterolemie
+ hipertrigliceridemie
+ clinic edeme
unele modificari sangvine pot lipsi daca:
debutul sdr. nefrotic este recent, in caz de
malnutritie (normo- sau hipo-colesterolemie, dar
hipoalbuminemie prezenta), in caz de boli cu
hipergamaglobulinemie (proteine totale normale sau
crescute, dar albumina redusa)
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Raportul proteinurie/creatininurie
se coreleaza bine cu proteinuria/24 de ore avantajul rapiditatii nu necesita colectarea urinii/24h mai fidela la pacientii cu insuficienta renala decit
proteinuria/24 ore aplicabil si in cazul pacientilor necooperanti sau al celor
incontinenti. persoanele sanatoase - raport < 0,2 (aproape) orice tip de boala renala - valori intre 0,2 - 3,5. sindrom nefrotic > 3,5
Deoarece pacientii cu proteinurie glomerulara si functie renala pastrata au un ritm circadian variabil pentru proteinurie, cu maximum de excretie ziua si minimum în timpul noptii, dar cu o excretie constanta de creatinina, timpul de colectare a probei simple poate semnificativ afecta raportul proteine/creatinina. Pentru acest motiv este de dorit totdeauna sa se colecteze proba în acelasi moment al zilei, de ex. între 7-9 dimineata.
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Microalbuminuria
Excretia urinara de albumina “fiziologica”
< 30 mg/24 ore
Microalbuminuria 30 -300 mg/dl
Raport microalbuminurie/creatininurie
MA marker precoce al afectarii renale in DZ
si HTA
marker al disfunctiei endoteliale si vasculare
generalizate
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MA/PU ca factori de risc pentru mortalitatea CV si cea generala
Muntner P et al. J Am Soc Nephrol 2002 13:745-753
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Alte investigatii
Imunograma (det. cantitativa a IgA, IgG,
IgM)
Electroforeza serica - proliferare (peak)
monoclonala? albuminemie? fractiunile
alfa si beta? -sugestii pentru etiologia
sdr. nefrotic
imunofixarea - proteine monoclonale
(MM, MW) - nu proteina Bence-Jones
(depasita si cu sensibilititate foarte
redusa)!
Urocultura/antibiograma
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Determinarea functiei excretorii renale
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Determinarea functiei excretorii renale
Ureea sg. - ieftină, uşor de efectuat
uree creatinină ?
Valori “normale”
uree 20-40 (50) mg/dl
creatinina 0,6 -1,2(1,4) mg/dl
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Valori “normale”
uree 20-40 (50) mg/dl
creatinina 0,6 -1,2(1,4) mg/dl
dar...
depind de masa musculara, nutritie, functia hepatica
hipercatabolism, rhabdomioliza
creatinina incepe sa creasca in momentul in care cel putin 50% din functia excretorie renala s-a redus!
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Valorile creatininei serice pot fi inselatoare...
Creatinina serica! 1,2 mg/dl
Clearance-ul creatinic! 35 ml/min versus 100 ml/min
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Relatia creatinina serica/ clearance creatininic
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Clearance-ul creatininic
estimeaza rata de filtrare glomerulara (functia excretorie renala)
mult mai fidela decit valoarea serica a creatininei
stiintific: metode sofisticate, clearance inulinic, izotopi etc
clinic:
determinarea prin colectarea urinii si raportare creatinina serica/creatinina urinara, functie de volum si de timp
determinarea prin formule
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Evaluarea in spital a clearance-ului creatininic
Cl cr (ml/min) = creatinina urinara (mg/dl) x volum urinar (ml/24h) /Cr serica (mg/dl) x 1440 (= min/24 ore)
N (B) = 97-137 ml/min/1,73 mp
N (F) = 88 -128 ml/min/1,73 mp
creatinina urinara = 15-25 mg/kgc/zi (B) /12,5-20 mg/kgc/zi (F)
(si in singe)- masa musculara , virsta , colectare improprie, malnutritie
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Determinarea functiei excretorii renale prin formule de calcul
Formula Cockroft-Gault:
Clcr = (140 - vârsta) x G* (x 0,85 la F)
72 x Crea serica
* G = greutatea ideală
functia renala “reala”
dozarea medicamentelor
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Formule de calculare a clearance-ului creatininic
Formula MDRD Clearance-ul creatininic (ml/min/1.73m2)
= 186 x [creatinina serică (mol/l) x 0.0113]-1.154 x vîrsta (ani)-0.203
(x 0.742 în cazul femeilor)
Creatinina serica (mol/l) = 88,4 x creatinina serica (mg/dl)
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Dozarea medicamentelor functie de clearance-ul creatininic
Ex. vancomicina - antistafilococic major
doza uzuala -la functie renala normala2 x1 g pe zi!
doza la pacienti cu insuficienta renala terminala
1 g la 3-7 zile!
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Clasificarea bolii cronice de rinichi
Stadiu Descriere RFG (ml/min/1,73 mp)
1. Leziune renala 90
cu RFG N sau
2. Leziune renala cu 60-89
usoara a RFG
3. moderata a RFG 30-59
4. severa a RFG 15-29
5. Insuficienta renala sev. < 15 sau
necesar de dializa
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Boala renala cronica - descoperita (relativ) recent ca o problema de sanatate publica
Foley R et al. Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES III study. Mayo Clin Proc 2005 Oct;80 (10) :1270-7.
15.387 de subiecti adulti neinstitutionalizati
rata de filtrare glomerulara (RFG):
>90 ml/min/1.73 m2 (normala!) - 65.4% !! 60-89.9 ml/min/1.73 m2 (BRC std. II) - 27.9% !! 30-59.9 ml/min/1.73 m2 (BRC std. III) - 6.2% !! <30 ml/min/1.73 m2 (BRC std. IV-V) - 0.5% !!
prevalenta factorilor de risc CDV si a bolii CDV in crestere cu gradul disfunctiei renale
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Prevalenta bolii CDV la pacientii cu BRC- relatie directa intre gradul afectarii renale si afectarea cardiovasculara
Slipak et al, Kidney Int 2002 Bare negre - boala CV manifesta clinic
Bare gri - boala CV subclinica
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Reevaluarea trial-urilor “cardiovasculare” :o prevalenta neobisnuit de ridicata a BRC
Pina la 64%
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Mesaje “de luat acasa”
Proteinuria: factor major de progresie a bolii renale factor major de progresie a insuficientei renale cronice pacientii cu proteinurie/mircoalbumiurie - morbiditate si
mortalitate cardiovasculara mare ex. sumar de urina - obligatoriu la pacienti internati, indispensabil la pacientii cu mare risc de boala renala (DZ,
HTA), obligatoriu anual la controale de rutina
proteinuria cantitativa la toti pacientii cu proteinurie semicantitativa prezenta
pacientii cu proteinurie severa si pacientii cu proteinurie usoara/moderata persistenta -obligatoriu adresati nefrologului -pentru investigatii si tratament
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Mesaje “de luat acasa”
Evaluarea functiei excretorii renale: obligatorie la pacienti internati, indispensabila la pacientii cu mare risc de boala renala (DZ,
HTA), obligatorie anual la controale de rutina uree, creatinina, (acid uric) calcularea clearance-ului creatininic! (simplu! - formula
Cockroft-Gault functia renala “reala”, dozarea medicamentelor
functie renala redusa - IRA? (atentie la iatrogenie!), IRC functie renala redusa persistent - IRC
risc de progresie! risc cardiovascular foarte mare!
Adresare la nefrolog!!! (investigatii si tratament)