NEFROPATII VASCULARE

LIGIA PETRESCU

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); 1123% (la pac cu coronarografie)

Anatomie patologica
Interstitial fibrosis, tubular atrophy, glomerulosclerosis (including focal segmental glomerulosclerosis), periglomerular fibrosis arteriolar abnormalities (hialinosclerosis, atheroembolism). atherosclerotic nephropathy

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 AII-RB therapy (> 30% increase in serum creatinine) Asymmetrical kidneys on imaging

DIAGNOSIS OF ARVD (2)

Other Unexplained acute pulmonary oedema or congestive cardiac failure Femoral, renal, aortic or carotid bruits Severe retinopathy History of extra-renal vascular disease Hypokalaemia Neurofibromatosis

DIAGNOSIS OF ARVD (3)

DRASTIC The most powerful predictors for detecting lesions of at least 50%: age, symptomatic vascular disease, elevated cholesterol the presence of an abdominal bruit.

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)

PARACLINIC (1)
1. Cresterea Cr. post IECA - specificitate , sens 2. Echo 2D + Doppler color (Dupplex) Velocitate sistolica de varf in AR cu > 2,5 x SD, raport velocitate Ao/velocitate AR > 3,5 intraparenchimatos: puls parvus et tardus; IR<0.45 Sensibilitate = 95-98%, specificitate = 90%, Avantaje: noninvaziva, repetabila, fara injectare de droguri nefrotoxice Dezavantaje: operator-dependenta, durata (3090), imposibila la obezi Indicatia preferentiala: IR moderata/severa

PARACLINIC (2)
3. Scintigrafia renala + test la captopril Marker: 99Tcm DPTA (Cr.. < 1,8) sau MAG (Cr. = 1,83 mg%) Sensibilitate 78-90%, specifictate 88-95% Avantaje: noninvaziva, repetabila, fara injectare de drog nefrotoxic Dezavantaje: risc de tromboza arteriala, nespecifica (atesta scaderea reninemiei consecutiv FG) Indicatia preferentiala: obezi 4. RMN - angiografia Sensibilitate 83-92%, specifictate 97-100% Avantaje: noninvaziva, repetabila, fara injectare de drog nefrotoxic Dezavantaje: nu detecteaza stenoza in ramurile secundare

PARACLINIC (3)
5. CTs-angiografia Sensibilitate 67-92%, specifictate 84% Avantaje: imagine tridimensionala Dezavantaje: estimare moderata a gradului stenozei, inj. subst. nefrotoxica Arteriografia selectiva cu substractie digitala Avantaje metoda de electie Inconveniente: Injectare de drog nefrotoxic Risc de embolii colesterolice Estimarea aproximativa a gradului stenozei (20%) Corelatie modesta cu evolutia post-revascularizatie

TREATMENT OPTIONS IN ARVD (1)

Few topics provoke more controversy between nephrologists and interventional cardiologists than management of atherosclerotic renovascular disease

TREATMENT OPTIONS IN ARVD (2)

Medical treatment Limiting the progression of atheromatous disease and chronic kidney disease
vigorous control of hypertension and hyperlipidemia, diabetes control use of antiplatelet agents, cessation of smoking lifestyle modification (including reduced dietary intake of salt and increased exercise). attention to the complications of renal insufficiency

TREATMENT OPTIONS IN ARVD (3)

CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions)

TREATMENT OPTIONS IN ARVD (4)

Antihypertensive therapy Is there an ideal blood pressure target that confers maximal cardiovascular protection? In CORAL, the target blood pressure is 140/ 90 mm Hg ; 130/80 mm Hg is recommended for patients with hypertension and diabetes or renal disease. Is there a specific antihypertensive regimen that provides cardiovascular benefits beyond just lowering blood pressure?

TREATMENT OPTIONS IN ARVD (5)

First-line agent
Angiotensin receptor antagonist First-line agent if ARB not tolerated - ACE inhibitor especially for those with proteinuric chronic parenchymal disease, and those with coexisting coronary artery disease and cardiac dysfunction.

Second-line agent
Thiazide diuretic Combinations with ARB/ACE may be available Use loop diuretics for patients with serum creatinine 2 mg/dL

Third-line agents (function of comorbidities)

Calcium channel blocker Beta Blocker Alfa Blocker Vasodilator

TREATMENT OPTIONS IN ARVD (6)

Dyslipidemia Treatment in terms of cardiovascular risk RAS is considered a coronary artery disease equivalent. Third Report of the
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

Goal of therapy low-density lipoprotein cholesterol <100 mg/dL some suggesting a target of < 70 mg/dL Statins effects independent of lipid-lowering stabilize, slow progression or even induce regression of atherosclerotic plaque reduction of proteinuria

TREATMENT OPTIONS IN ARVD (7)

Diabetes Mellitus HbA1c of <7 mg/dL with oral agents and/or insulin medical nutrition therapy; physical activity; multidisciplinary foot and eye care; Chronic Renal Insufficiency Tight control of blood pressure, dyslipidemia, diabetes; manage anemia; hyperparathyroidism. (Guidelines) Antiplatelet Agents Although there are no direct data in patients with RAS, administration of an antiplatelet agent is required in CORAL and recommended for all patients with RAS. Aspirin, Clopidogrel or Ticlopidin.

TREATMENT OPTIONS IN ARVD (8)

Effect of the Medical Therapy Intervention reduce cardiovascular risk progression to end-stage renal disease actually does not respond very well to medical therapy

TREATMENT OPTIONS IN ARVD (9)

Surgical treatment revascularization nephrectomy of small kidneys with relatively complete arterial occlusion.

TREATMENT OPTIONS IN ARVD (9)

Evidence for renal revascularization Randomized Trials in Renal Artery Stenosis Intervention
Year Weibull 1993 Plouin 1998 Webster 1998 van de Ven 1999 van Jaarsveld 2000 n Medical Balloon 58 X 49 X 55 X 84 X 106 X Stent End Points X BP/renal function X BP X BP/renal function X Patency/BP/renal function X BP/renal function

Benefits: A modest improvement in blood pressure control no improvement in renal function.

TREATMENT OPTIONS IN ARVD (10)

Definite indications for renal revascularization Recurrent flash pulmonary oedema Severe hypertension resistant to all medical therapy. When a patient who requires ACE-I or AII-RB therapy (e.g. for cardiac failure) presents with significant ACE-I-related uraemia. RAO in a reasonably sized kidney

TREATMENT OPTIONS IN ARVD (11)

CONTROVERSIES Effect of Revascularization on Blood Pressure Revascularization may fail to cure hypertension In long-standing hypertension, secondary processes that sustain hypertension Vascular remodeling, atherosclerosis, ischemic damage to the poststenotic kidney, hypertensive injury to the nonstenotic kidney

PROGNOSIS OF PATIENTS WITH ARVD

Major mortality from cardiovascular complications; risk of death is almost six times that of developing ESRD Mailloux et al. showed that patients with ARVD receiving dialysis had a median survival of 27 months and an average 5-year survival of only 18%. Fiveyear survival in two prospective studies was 7% lower in patients with renal artery stenosis than in wellmatched essential hypertensives and 23% lower than in the general population (Wollenweber, Conlon et al.).

NEFROANGIOSCLEROZA
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
Normal High normal Hypertension Grade 1 (mild) Grade 2 (moderate) Grade 3 (severe) Isolated systolic hypertension

< 120
120-129 130-139

< 80
80-84 85-89

140-159 150-179 180 140

90-99 100-109 100 < 90

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. >60 ani la populaia caucazian 45-64 ani la populaia afro-american. 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.

2. Vrsta medie la diagnostic

3. Hipertensiune arterial:

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

DIFERENTA NEFROANGIOSCLEROZA/ NEFROPATIE ISCHEMICA

Varsta (ani) Teren Rasa Cauza Mecanism Declinul FG Proteinurie Scopul terapiei
Supravietuire in dializa

40 60 HTA Neagra HTA + fibroza vasc. Pres. perf. Lent Prezenta TA + antifibrozant
BUNA

60 Ateromatoza Caucaziana Ateromatoza AR Pres. perf. Mai rapid Absenta Revascularizatie + antitrombotic, IECA?!
CATASTROFICA

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.