NEFROPATII VASCULARE

nefropatia ischemica prin stenoza de artera

renala
nefroangioscleroza benigna
nefroangioscleroza maligna
boala renala ateroembolica

NEFROPATIA ISCHEMICA
Stenoza aterosclerotica AR HTARV , NEF ISCH
Boala caracterizata prin reducerea semnificativa a ratei FG
consecutiv unei stenozari hemodinamic semnificative
(>75%) a arterei renale (in cazul rinichiului solitar) sau a
ambelor AR (daca exista ambii rinichi)
PREVALENTA NEF ISCH putin cunoscuta; arteriografic:
14-42% (coasociere cu boala vasculara periferica); 11-23%
(la pac cu coronarografie)

CLINICA
3 SITUATII:

Asimptomatic clinic
IR
HTA + ateroscleroza sistemica (claudicatie /
cardiopatie ischemica / ICC)
Profilul caracteristic: B, >60 ani, fumator, dislipidemic,
hipertensiv +/- flash EPA

DIAGNOSIS OF ARVD (1)

Clinical features suggestive of renovascular disease
Hypertension
Abrupt onset of hypertension in patients aged <30 years (suggestive of
FMD) or >50 years (suggestive of ARVD)
Absent family history of hypertension
Accelerated or malignant hypertension
Resistance to therapy (3 drugs)
Hypertension may be absent, particularly in patients with chronic
cardiac disfunction.!!!

Renal abnormalities
Unexplained renal failure in patients aged >50 years
Elevation in plasma creatinine level after the initiation of ACE-I or AIIRB therapy (> 30% increase in serum creatinine)
Asymmetrical kidneys on imaging

CAUZE DE INSUFICIENTA RENALA ACUTA

1. Tratament IECA / ARA = 57%
6-38% in literatura
Hipovolemia, hTA
Reversibila (!)
2. Tromboza arteriala / intrarenala = 28.5%
3. Ateroembolismul colesterolic = 4.7%
4. nefrita interstitiala, radiocontrast = 4.7%
ATEROEMBOLISM: tablou pseudovasculitic:
- livedo reticularis
- placi bleu/purpurii cutanate la membrele inferioare
- paloare/necroza a degetelor membrelor inferioare
- eozinofilurie, hipocomplementemie
cresteri bruste ale TA AIT (afectarea vaselor mici)
deteriorarea functiei renale

OCLUZIA ACUTA A ARTEREI

RENALE
IRA
Triada:
Durere severa in flanc
Hematurie
Crestere brusca a TA
+ anurie (in caz de rinichi unic sau ocluzie
bilaterala)

TREATMENT OPTIONS IN ARVD (3)

CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic
Lesions)

NEFROANGIOSCLEROZA HT
DEFINITIE
afectare renala care poate fi iniiat, perpetuat sau
accelerat ca o consecin a unor componente ale PA
(sistolica, diastolica, presiunea pulsului, variabilitatea
PA).

INCIDENTA

SUA 28.3% (28% Afro-Americani, 24% la Caucazieni)

Europa 12%
Romania 6%

Definition and Classification of Blood

Pressure Levels (ESH)
Category

Systolic (mmHg)

Diastolic (mmHg)

Optimal

< 120

< 80

Normal

120-129

80-84

High normal

130-139

85-89

Grade 1 (mild)

140-159

90-99

Grade 2 (moderate)

150-179

100-109

Grade 3 (severe)

180

100

Isolated systolic hypertension

140

< 90

Hypertension

Mecanisme patogenice
nefroangiscleroza benigna
Autoreglare aberanta
Pierderea capacitatii de autoreglare a fluxului sanguin renal la nivelul arteriolei
aferente conduce la transmiterea presiunii crescute catre glomerulii ramasi
neprotejati, avand drept consecinta hiperfiltrarea , hipertrofia glomerulara si in
final GSFS

Mecanisme protrombotice
interventia factorilor genetici modulatori ai trombozei in producerea sclerozei
vasculare.

Greutate redusa la nastere si reducerea numarului de nefroni

Factori genetici
Alelele D ale genei ECA

Sindrom dismetabolic
Blood pressure 130/85 mm Hg;
Low high-density lipoprotein cholesterol: < 1.0 mmol/L (40 mg/dL) in men; <
1.2 mmol/L (46 mg/dL) in women;
High triglycerides: > 1/7 mmol/L (150 mg/dL);
Altered fasting glucose: 5.6-6.9 mmol/L (102-125 mg/dL); and
Abdominal obesity: waist circumference > 102 cm in men; > 88 cm in women.

CRITERII DE DIAGNOSTIC (1)

1. Anamnez:

Istoric familial de HTA;

Absena oricrei suferine renale nainte de instalarea HTA.

2. Vrsta medie la diagnostic

>60 ani la populaia caucazian

45-64 ani la populaia afro-american.

3. Hipertensiune arterial:

fr afectare renal la momentul diagnosticului HTA;

de lung durat, la momentul diagnosticului nefrosclerozei
benigne;
valori medii/moderate;
retinopatie i hipertrofie ventricular stng la momentul
diagnosticului nefrosclerozei benigne.

CRITERII DE DIAGNOSTIC (2)

4. Proteinurie:

<0,5gr/24 ore sau raportul proteinurie/creatininurie<2;

la valori ale creatininei serice >2,5mg/dL se accepta
proteinurii>2g/24 ore.

5. Sediment urinar srac, necaracteristic.

6. Funcie renal:

normal la momentul diagnosticului HTA;

cretere insidioas a creatininei serice;
valori crescute ale acidului uric seric (independent de
diuretice);
fracie de filtrare crescut.

ANATOMIE PATOLOGICA (1)

Rinichii sunt egali i au dimensiunile reduse
proporional cu gradul insuficienei renale.
Caracteristic este suprafaa fin granular, trdnd
suferina arterelor mici i a arteriolelor
Leziunile arteriale
arterele arcuate, interlobulare, arteriolele aferente
Leziunea arterial caracteristic este
nefroangioloscleroza, cu dou componente:
a) rspunsul hipertrofic
ngroarea intimal fibro-elastic,
dedublarea laminei elastice
hipertrofia/hiperplazia mio-fibroblastic a mediei
b) hialinoza

ANATOMIE PATOLOGICA (2)

Leziunile glomerulare
glomeruloscleroz focal global
glomeruloscleroz focal segmentar
a) Glomeruli obsolesceni:spatiul Bowman este ocupat de colagen, material
PAS pozitiv, iar ghemul de capilare glomerulare este retractat

b) Glomeruli solidificai: intregul ghem capilar este solidificat, in absenta

modificarilor colagenice din spatiul capsular

c) Glomeruli pe cale de dispariie: sunt glomeruli global sclerotici, cu

absenta sau disparitia partiala a capsulei Bowman

Leziunile tubulo-interstiiale
atrofie tubular,
fibroz interstiial
infiltrat inflamator cu macrofage i limfocite

NEFROANGIOSCLEROZA MALIGNA (1)

Definitie
Este un sindrom caracterizat prin HTA sever i fix (PAS
230 mmHg i PAD 140 mmHg), encefalopatie
hipertensiv, fund de ochi cu hemoragii, exudate i edem
papilar (grad III i IV), deteriorare rapid a funciei cardiace
i renale, anemie hemolitic microangiopatic.
Anatomie patologica
n fazele iniiale, rinichii sunt normali sau usor mrii de
volum, pentru ca n final s ajung micorai simetric.
Suprafaa renal este acoperit de mici zone hemoragice,
izolate sau congruente.

NEFROANGIOSCLEROZA MALIGNA (2)

Aspectul microscopic
1. Leziunile vasculare sunt cantonate la nivelul arterelor interlobulare
i al arteriolei aferente:
Endarterita proliferativa.(arterele interlobulare)
Necroza fibrinoid (arteriola aferent)
2. Leziunile glomerulare: necroz parcelar a anselor glomerulare,
depozite fibrinoide i proliferare variabil a celulelor endoteliale i
ale capsulei Bowman. Cicatrizarea se face caracteristic prin
nlocuirea flocculus-ului cu un bloc de fibroz nconjurat la periferie
de podocite. Sunt afectai ntre 5-30% dintre glomeruli.
3. Leziunile tubulare : atrofie tubular, fibroz i infiltrat inflamator
cronic. Necroza tubular acut este un aspect rar ntlnit n NASM.

Clinic
Reflect afectarea visceral multipl, caracteristic
acestui sindrom.
1. Stare general alterat, paloare tegumentar, scdere
ponderal important.
2. Encefalopatia hipertensiv; Se nsoete de modificri ale
FO de gradul IV i III.
3. Cardiopatia hipertensiv
4. Manifestrile renale constau n proteinurie variabil
neselectiv (ntre 0,4 - 20 g/24 ore), hematurie
microscopic sau macroscopic, degradare a funcie
renale care poate fi acut oliguric, subacut sau cronic.

Paraclinic
1. Modificrile hematologice sunt complexe: anemie de tip
microangiopatic (cu schizocite i fragilitate crescut a
hematiilor), trombocitopenie. VSH este crescut.
2. Modificrile electrolitice constau n hipokalemie,
hiponatremie i alcaloz pasager, prin creterea
compensatorie a reteniei de bicarbonai.
3. Explorrile renale: sumarul de urin asociaz
proteinurie dozabil cu hematurie i leucociturie,
cilindri hialini, granuloi, hematici sau leucocitari.
Valorile produilor de retenie azotat cresc rapid, pe
msura scderii concomitente a fluxului plasmatic renal
i a filtratului glomerular.
4. Dozarea hormonal relev creteri importante ale
reninei, angiotensinei i aldosteronului plasmatic.
5. Puncia biopsie, practicat numai dup scderea valorilor
tensionale, relev tabloul histologic specific HTAM.

TRATAMENT
Tratamentul de urgen
scderea rapid a valorilor presiunii arteriale, folosind
medicaie administrat pe cale parenteral.
La pacienii cu encefalopatie hipertensiv valorile
presionale vor fi sczute lent, n 24 ore i la nivele de
minimum 170/100mmHg.
Se folosesc, n ordinea eficienei, nitroprusiatul de sodiu,
diazoxidul, hidralazina, diuretice de ans.
Tratamentul de ntreinere
Va include o schem de 2-4 antihipertensive, asociate
astfel nct s se obin o scdere a presiunii arteriale la
valori normale (<120/80mmHg) dup 2-3 luni, alegnd
IEC de prim intenie.

PATOLOGIA RENAL N SARCIN

Nefropatia gravidic primar este un sindrom hipertensiv
aprut de novo la o primipar n al treilea trimestru de sarcin
asociind proteinurie i edeme.
Sinonime: Sindromul vasculo-renal gravidic; Toxicoza (toxemia)
gravidic; Preeclampsia (marker lezional endotelioza);
Disgravidia pur; Gestoza genuin tardiv
Nefropatia gravidic secundar relev suferina renal
preexistent sarcinii agravat sau scoas din laten de ctre
sarcin nc din primul trimestru.
Sinonime: Preeclampsia supraadugat;
sarcina;Gestoza secundar

HTA agravat

de

NEFROPATIA GRAVIDIC PRIMAR

apare dup spt 20-a de gestaie i retrocedeaz postpartum nerepetndu-se la sarcinile ulterioare
sd. hipertensiv este definit de valori ale TA > 14/8 cm Hg
proteinuria - element definitoriu - poate depi 5g/24h
edemele consecin a proteinuriei, dar i a mecanismelor
complexe endocrino-umorale
elementul fiziopatologic constant
=
vasospasmul
generalizat
elementul histopatologic constant = endotelioza
uneori anomalii de coagulare

NEFROPATIA GRAVIDIC PRIMAR

Simptomatologia
Elemente definitorii:

apariia la primipare;
instalarea n ultimul trimestru al sarcinii;
retrocedarea postpartum;
lipsa repetrii la sarcina ulterioar.

Simptome subiective: cefalee (intensificat nocturn),

iritabilitate, irascibilitate, tulburri vizuale (fosfene, scotoame,
diplopie, scderea acuitii vizuale) sau auditive (tinnitus,
acufene etc.)
Semne obiective:
HTA > 145/90mmHg;
sd. edematos;
cardiomegalie, tahicardie cu ritm de galop;
hepatomegalie dureroas (de staz);
paloare prin hemodiluie;

NEFROPATIA GRAVIDIC PRIMAR

Investigaiile de laborator
Ex. de urin:
oligurie discret pn la oligoanurie;
proteinurie neselectiv ntre 1 i 10 g/24h;
sedimentul urinar: rare hematii, cilindrii, rel. frecvente L i
epitelii
Explorarea funcional renal:
uricemia > 4,5mg/dL = test predictiv !
produi de retenie azotat n general normali;
scdere relativ FSR, FPR, FG i FF
Tulburrile de coagulare (hipercoagulabilitate moderat =
CIVD cronic)
cresc factorii I, II, V, VII, VIII, IX i X;
crete adezivitatea plachetar;
inhibiia fibrinolizei;
creterea PDF

NEFROPATIA GRAVIDIC PRIMAR

Complicaii
Complicaii neurologice
Eclampsia = accident sever cu risc vital major pentru mam
i ft ce complic stare de preeclampsie;
= cretere paroxistic a TA encefalopatia hipertensiv
sever dominat de convulsii i, n final, stare de com.
Incidena = 5-10% din primiparele cu NGP
Mortalitatea fetal n eclampsie este 40-50% !
Complicaii obstetricale
Avortul
Moartea ftului in utero
Hematom retroplacentar
Hipotrofia sau prematuritatea fetal
Complicaii renale
IRA din ultimul trimestru al sarcinii

NEFROPATIA GRAVIDIC PRIMAR

Tratamentul medical

Tratament igieno-dietetic

Tratamentul medicamentos:
1 tratamentul anti-HTA se va aplica la tensiuni peste 17/11cmHg
Dopegyt, Aldomet 250-1000mg/24h;
Hidrazinoftalazinele 25-100mg/24h;
Clonidina 0,1-0,3mg;
Antagonitii de Ca (nu nainte de spt 20!)
Prozosin (Minipress);
Diazoxidul 300mg i.v. n marile urgene
2 medicaia diuretic - numai n situaii speciale (IC, EPA, eclampsie)
3 medicaia
antiadezivo-agregant
i
anticoagulant
(controversat):
Aspririna, Dipiridamol, Prostaciclina, Heparina etc
4 medicaia sedativ (barbiturice, benzodiazepine)

NEFROPATIA GRAVIDIC PRIMAR

Tratamentul eclampsiei
Declanarea travaliului mpiedic apariia eclampsiei dar incumb o
mare responsabilitate n decizie.
Sub vrsta de 34 spt se temporizeaz declanarea travaliului i se
monitorizeaz strict pacienta. Se aplic antihipertensive, diuretice,
Dextran, Manitol etc.

Tratamentul convulsiilor
Sulfatul de magneziu 4g i.v. n bolus + 5g i.m. profund, doz
repetat n funcie de evoluie la 4-5 ore interval
Monitorizarea = verificarea ROT, a diurezei i a respiraiei !
Fenobarbitalul 0,10g i.m. la 2-4h
Amital sodic 0,25g i.v. lent
Diazepam 20mg i.v. lent
Mialgin 100mg i.m.

Tratamentul obstetrical = evacuarea uterului

Diabetic nephropathy
DN is the leading cause of CKD in the industrialised world.
One of the most significant long-term complications in terms of morbidity
and mortality for individual patients with diabetes.
Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD)
cases in the United States.
Although both type 1 diabetes mellitus (IDDM) and type 2 diabetes mellitus
(noninsulin-dependent diabetes mellitus [NIDDM]) lead to ESRD, the
great majority of patients are those with NIDDM.
The glomeruli and kidneys are typically normal or increased in size initially,
thus distinguishing DN from most other forms of chronic renal insufficiency,
wherein renal size is reduced (except renal amyloidosis and polycystic
kidney disease).
DN = Diabetic Renal Disease - which progresses through five predictable stages.

Definition
A microvascular complication of diabetes
marked by albuminuria and a deteriorating
course from normal renal function to ESRD.

Albuminuria 30 - 300 mg/day got called

Microalbuminuria
it predicts the development of clinical nephropathy
one positive is not enough in the low range
detected by measuring the albumin/creatinine ratio on a
spot urine sample

Natural History

Pathology
Expansion of mesangial matrix with diffuse
and nodular glomerulosclerosis
(Kimmelstiel-Wilson nodules)
Thickening of glomerular and tubular BM
Arteriosclerosis and hyalinosis of afferent
and efferent arterioles
Tubulointerstitial fibrosis

Pathogenesis
Exposure to the diabetic milieu
Hyperglycemia

Induce mesangial expansion and injury

Increased activity of growth factors
Activation of cytokines
Formation of ROS
accumulation of advanced glycosylation endproducts in tissues

Accumulation of ECM components, such as collagen

Genetic predisposition to or protection from diabetic
nephropathy
Differences in prevalence of microalbuminuria, ESRD in different patient
populations
Only half of patients with poor glycemic control will develop diabetic
nephropathy
Family studies

Multiple genes may be involved

Stage 1 (very early diabetes)

Increased demand upon the kidneys is indicated by an above-normal
glomerular filtration rate (GFR).
Hyperglycemia leads to increased kidney filtration (see later)
This is due to osmotic load and to toxic effects of high sugar levels on
kidney cells
Increased Glomerular Filtration Rate (GFR) with enlarged kidneys

Stage 2 (developing diabetes)

Clinically silent phase with continued hyper filtration and
hypertrophy
The GFR remains elevated or has returned to normal, but
glomerular damage has progressed to significant
microalbuminuria (small but above-normal level of the
protein albumin in the urine).
Significant microalbuminuria will progress to end-stage
renal disease (ESRD).
Therefore, all diabetes patients should be screened for
microalbuminuria on a routine basis.

Stage 3 (overt, or dipstick-positive diabetes)

Glomerular damage has progressed to clinical albuminuria.

Basement membrane thickening due to AGEP
The urine is "dipstick positive," containing more than 300
mg of albumin in a 24-hour period.
Hypertension (high blood pressure) typically develops
during stage 3.

Stage 4 (late-stage diabetes)

Glomerular damage continues, with increasing

amounts of protein albumin in the urine.
The kidneys filtering ability has begun to decline
steadily, and blood urea nitrogen (BUN) and
creatinine (Cr) has begun to increase.
The glomerular filtration rate (GFR) decreases about
10% annually. Almost all patients have hypertension
at stage 4.

Stage 5 (end-stage renal disease, ESRD)

GFR has fallen to <15 ml/min and renal

replacement therapy (i.e., haemodialysis,
peritoneal dialysis, kidney transplantation) is
needed.

DIAGNOSIS/SCREENING

Spot urine albumin : creatinine ratio

24 hour urine collection
Dipstick

TREATMENT

Glycemic control
Hypertension control
Dietary protein restriction
RAS blockade- IECA/ ARBs
BARDOXOLONE ??!!

Tratamentul substitutiv al IRC

Hemodializa
Dializa peritoneal
Transplantul renal

Fazele tratamentului IRC

HD i DPCA

Indicaii de iniiere de urgen a

dializei
Insuficiena renal cronic cu tulburari ale echilibrelor

hidro-electrolitic i acido-bazic:
severe;
necorectabile prin mijloacele terapeutice conservatoare;
Insuficiena renal cronic cu simptomatologie intens sau
cu risc vital:
pericardit;
insuficien cardic rezistent la terapia clasic;
malnutriie;
tulburri neurologice.

Contraindicaiile HD
Relative:
Vrsta naintat (peste 75 ani);
Boli cu deficiene funcionale severe ale altor organe
(insuficien cardic cu disfuncie sistolic sever,
insuficien hepatic, insuficien respiratorie etc);
capital vascular deficitar.
Absolute:
IRC asociat cu cancer cu metastaze/generalizat sau
cu prognostic de supravieuire <1 an;
bolile psihice majore;
alergia la heparin.

Indicaii difereniale DPCA/HD

1. Capital vascular deficitar;
2. Bolnavi de diabet zaharat;
3. Bolnavi cu vrste extreme;
4. Instabilitate hemodinamic
datorat/accentuat de hemodializ;
5. Sindrom hemoragipar;
6. Alergie la heparin.

Contraindicaiile DPCA
Absolute:
Rezecii mezenterice ntinse;
Tumori abdominale mari;
Ileus;
Obezitate extrema;
Comunicri pleuroperitoneale largi
nnascute/dobndite;
Intervenii chirurgicale cu
deschiderea peritoneului
posterior;
Enterostomii;

Cisto-/ureterostomii;
Insuficien respiratorie;
Cecitate;
Bolnavi sub 18 ani, fr
aparintori care s i asume
responsabilitatea terapiei;
Psihoze, demen, retardare
mintal,
Paralizii, osteo-artropatii cu
deficit funcional al minilormpiedicnd efectuarea
schimburilor.

Contraindicaiile DPCA
Relative:
Cicatrici ntinse ale peretelui abdominal;
Hernii;
Radioterapie pe abdomen n antecedente;
Discopatii lombare;
Drenaj post-operator al cavitii abdominale;
Sarcina avansat;
Polichistoz renal cu dimensiuni foarte mari ale
rinichilor;
Diverticuloza colonic.

RENAL TRANSPLANTATION
AN OVERVIEW

Patients Selection For Kidney

Transplanatation
All patients with ESRD are condidates
for KT unless
Systemic malignancy.
Chronic infection.
Severe cardiovascular disease.
Neuropsychiatric disorder.
Extremes of age (relative).

An adult donor kidney transplanted to the left iliac

fossa of an adult recipient.

Kidney Donor

Living related.

Living unrelated (emotionally motivated).

Cadaveric (Brain-dead)
Beating and non-beating heart.

CRITERIA FOR LIVING DONOR

SELECTION
-

Blood relative.
Highly motivated.
ABO blood group-compatible.
HLA-identical or haploidentical with
negative cross-match.
Excellent medical condition with normal
renal function.

CRITERIA FOR CADAVER

DONOR SELECTION
-

Irreversible brain damage.

Normal renal function appropriate for age.
No evidence of preexisting renal disease.
No evidence of transmissible diseases.
ABO blood group-compatible.
Negative cross-match.
Best HLA match possible, particularly at the
DR and B loci.

Matching between Recepient And Donor

A- Tissue typing
Determined by 6 antigens located on cell surface
encoded for by the HLA gen located on the short arm of
chromosom 6.
Class I antigens (HLA-A and HLA-B) are expressed on the
surface of most nucleated cells.
Class II antigen (HLA-DR) are expressed on surface of
activated lymphocytes.
These 6 antigens are refered to as major transplant
antigens.
The match between donor and recepient can range from 0
to six.

Matching between Recepient And Donor

B- Cross matching

A laboratory test that determines weather a potential

transplant recepient has preformed antibodies against the HLA
antigens of the potential donor. (Donor Lymphocytest
+Recepient Serum)

A Final CM is mandatory

C- Compatible ABO blood group.

Factors Influencing The Longivity Of

Renal Allograft

Age
HLA matching
Delayed graft function
Ischemia time.
Number of acute rejection episodes.
Native kidney disease.
Ethnicity.
Others

Principles underlying current

immunosuppressive treatment
1- The benefits of a successful transplant

outweight the

risks of chronic immunosuppression.

2- Immunosuppressive therapy is required indefinitely.
3- Multidrug regimens are generally employed.
4- Large doses of immunosuppressant drugs are used in the
early transplant period.

Classes of Maintenance Immunosuppressive Drugs

Class
Immunophilin-binding
agents

Examples
Calcineurin inhibitors
Cyclosporine
Tacrolimus (FK506)
Calcinurin-independent agents
Sirolimus (rapamycin)

Glucocorticoids
Antimetabolites

Purine inhibitors: nonselective

Azathioprine
Purine inhibitors:lymphocyte selective
Mycophenolate mofetil (RS-61443)
Mizoribine*
Pyrimidine inhibitors
Brequinar*

Poorly understood mechanisms

Deoxyspergualin*
Leflunomide*
*Experimental or not yet approved by Food and Drug Administration (FDA).

Risks associated with chronic

Immunosuppression
1- Malignancy
2- Infection
3- Side effects of different drugs
(steroids, CsA, tacrolimus, MMF, ..)

Sonogram showing a lymphocele adjacent to a kidney.

Sonogram consistent with ureteral obstruction