A hipertenzv vesekrosodsrls megelzsrlSemmelweis Egyetem I. sz. Belgygyszati Klinika, BudapestDr. Barna Istvnegyetemi docens

A hypertensiv vesekrosodsrl s megelzsrl

dr. habil. Barna IstvnSemmelweis Egyetem I. Belklinika, Magyar Hypertonia Trsasg s Magyar Nephrolgiai Trsasg Elnksgi tagja Hziorvosi Szakmai Kollgium tagja

2012. jnius 1 Debrecen

Definci, klinikum

Endothelium srlsvazoaktv anyagok Lipid depozcicapillaris thr.Primer VesebetegsgHypertensiv vesekrosodsA vesekrosods pathomechanizmusaGlomerularis hypertensioHypertoniamakromolekulksejtproliferciMesangium srlsmatrixprodukciEpithelium srlsproteinuriavz irnti permeabilitasletkor Diabetes mellitus

Hypertonis vesekrosods - klinikum Hypertonia Lassan progredil veseelgtelensg MAU, mrskelt proteinuria ( < 1 g/nap) Vizeletledk inaktv UH - Cskken vesemret HyperuricemiaBta 2 globulin emelkedett

Hypertensiv vesekrosods megelzse, kezelse

Rizikmrs s besorols Ajnlott clvrnyomsrtkek

Nem gygyszeres kezelse

Dohnyzs (napi > 20 cigaretta) gyulladsos s nem-gyulladsos vesebetegsgben egyarnt gyorstja a progresszit, fokozott symp. tnus intraglom. nyoms endothel krosts NO szintzis , endothelin direkt toxikus hats a tubulus sejtekrereaktv oxign gykkglomerulus hyperperfusio, GFR , nagyobb veseatherosclerosisMicroalbuminuria 2-szer gyakoribb dohnyosok kzttDohnyzs elhagysa jelentsen cskkenti a veseelgtelensg kockzatt diabeteses s nem-diabeteses nephropathiban egyarntDohnyzs s a vesebetegsg progresszija

A protein-dita hatsa a progresszira az MDRD-vizsglatbanNEJM 1994;330:877n=585 0,58 g/kg vs. 1,3 g/kg

A protein-dita hatsa a progresszira: meta-analzisAJKD 1998;31:954 GFR 0,53 ml/min/v

A magas vrnyoms kezelsi alapelveiSzisztols s diasztols vrnyoms clrtkig trtn, fokozatos cskkentseEgyenletes, legalbb 24 rs hatstartam szerek preferlsaA napszaki ritmus korrekt belltsanappali/jszakai arny fenntartsajszakai hyper/hypotonia elkerlsereggeli meredek emelkeds kivdseA CV esemnyek: (stroke, ISzB, szvelgtelensg, vesekrosods, mortalits) megelzseA kialakult szvdmnyek (BKH, IMT/plakkok, proteinuria) mrsklse

100 vizsglat sszesen 2494, I-es s II-es tpus cukorbetegnek meta-regresszis analzise.* p < 0,05 a kalciumcsatorna-blokkolkhoz kpest. p < 0,05 a kontrollcsoporthoz kpest.A vrnyomscskkens, ill. az ACE-gtls proteinurira s vesemkdsre gyakorolt hatsa cukorbetegek esetbenKasiske BL et al. Ann Intern Med 1993;118:129-138.Logaritmikus vltozs a kiindulsi rtkhez kpestACECaABblKontrollProteinuria Albuminuria

RAAS gtlk vesevd hatsaMesangialis sejtproliferci cskken

Endothelium srlsvazoaktv anyagok Lipid depozcicapillaris thr.Primer VesebetegsgHypertensiv vesekrosodsA vesekrosods pathomechanizmusaGlomerularis hypertensioHypertoniamakromolekulksejtproliferciMesangium srlsmatrixprodukciEpithelium srlsproteinuriavz irnti permeabilitasletkor Diabetes mellitus

Cardiovascular Events in Patient SubgroupsDiabetesNo diabetesCurrent smokerNon-current smokerObeseNon-obeseLVHNo LVHOlder (> 60 years)Younger ( 60 years)FemaleMalePrevious vascular diseaseNo previous vascular diseaseRenal dysfunctionNo renal dysfunctionWith metabolic syndromeWithout metabolic syndrome1.000.801.50Amlodipine / Perindopril(BP 164.1/94.8 135.5/79.1 mmHg)Atenolol / Thiazide(BP 163.9/94.5 136.3/78.4 mmHg)0.700.90 2.9/1.7 mmHg

Perindopril/indapamide megelzi a vesekrosodst s elsegti a vesekrosods visszafejldstDe Galan BE et al. J Am Soc Nephrol 2009;20:883-892. Per-ind, perindopril/indapamide combination

ARB-k s vesevdelemStrippoli G, et al. Br Med J 2004;329:828-38.END STAGE RENAL DISEASEParving 2001w38 w39 w58 0/3890/201 Not estimableLewis 2001w5782/579101/569 33.350.80 (0.61 to 1.04) Brenner 2001w56 147/751194/762 66.650.77 (0.64 to 0.93)Total (95% CI)17191532 100.000.78 (0.67 to 0.91)Test for heterogeneity: c2=0.05, df=1, P=0.82, I2=0%Test for overall effect: z=3.18, P=0.001S. CREATININE DOUBLINGParving 2001w38 w39 w58 0/3890/201 Not estimableLewis 2001w5798/579135/569 40.190.71 (0.57 to 0.90)Brenner 2001w56 162/751195/762 59.810.84 (0.70 to 1.01)Total (95% CI)17191532 100.000.79 (0.67 to 0.93)Test for heterogeneity: c2=1.22, df=1, P=0.27, I2=18.2%Test for overall effect: z=2.91, P=0.004Favors agentFavors placebo or no treatmentNo of Patients with Event/Total No of PatientsAngiotensin II Enzyme InhibitorRelative Risk (Random) 95% CIPlacebo or No TreatmentWeight (%)Relative Risk (Random) 95% CI

ACEi vs. ARB: albuminuriaARBACEiARB ACEi (n)betterKunz R, Ann Intern Med. 2008;148:30

KalciumantagonistkCskkentik a renalis vascularis rezisztencit.Extacellulris mtrixkpzds gtlsa.Szabadgyk cskkents.Jl kombinlhat ACE-vel vagy ARB-vel, additv vrnyomscskkent hats.

Kalciumcsatorna blokkolkDihydropyridin nifedipine, amlodipine, felodipineLeghatkonyabb vrnyomscskkentkdemaPhenylalkylamin verapamilNegativ kronotrop, inotrop, ritmuszavarokban is jszkrekedsBenzothiazepin diltiazemLegkevesebb mh.legdrgbb

BENEDICTRuggenenti P. et al. NEJM 2004;351:1941-1951(NS)

BENEDICTRuggenenti P. et al. NEJM 2004;351:1941-1951p

DIURETIKUMOKcskken az oedemacskken a nehzlgzsn a terhelsi kapacitskzvetett kedvez mortalitsi hats

Diuretikumok thiazidok alkalmazsa vagy indapamidEssentialis hypertoniaIzollt szisztols s idskori hypertoniaObesitas, diabetes, metabolikus szindrmaNtrium-, vzretenciBalkamra hypertrophia, szvelgtelensgStroke utnEnyhe krnikus veseelgtelensgKALB, hyperaldoszteronizmus,

SSZEFOGLALS

Hypertenzv nephropathia kezelse:RAAS gtl kiegsztse kalciumcsatorna blokkolval vagy diuretikummal RAAS gtl (ACEI, ARB, DRI)Kalciumcsatorna blokkolThiazid-tpus diuretikumNephropathiaMetabolikus szindrmaPrediabetes, dyslipidemiaHyperuricemiaHypokalemiaNephropathiaHypervolemiaSzvelgtelensgAnyagcsere eltrs nincsDiabetes kockzata kicsiMancia,G. ESH Adv. Course St. Moritz 2012

Ksznm a figyelmet

********Antihypertensive treatment has been shown to slow the rate of declining renal function in patients with diabetic nephropathy (Lewis et al, 1993; Parving et al, 1993; Kasiske et al, 1993; Ismail et al, 1999). However, experiments in animal models of diabetes suggest that different antihypertensive agents may vary in their ability to prevent renal damage. Moreover, clinical trials looking at the effect of various antihypertensive agents on glomerular filtration rate (GFR) and proteinuria in patients with diabetes have shown conflicting results. The effects of ACE inhibitors in reducing urinary protein and preserving renal function in patients with diabetic nephropathy have been the most consistent, although questions remain about whether they actually provide better renal protection than other classes of agents. In patients with diabetic nephropathy, ACE inhibitors have been shown in some studies to provide superior antiproteinuric effects and superior reductions in the rate of decline in kidney function compared to beta blockers (Bjorck et al, 1992; Bakris et al, 1996), whereas other studies have failed to demonstrate any differences between these two classes of agents on the rate of decline of GFR (Nielsen et al, 1997; Lacourciere et al, 1993). Similarly, although ACE inhibitors may be more effective than calcium channel blockers (CCBs) in reducing albuminuria (Ismail et al, 1999), several studies have shown ACE inhibitors to have beneficial effects on GFR similar to those of nondihydropyridine CCBs (Bakris et al, 1996) and the dihydropyridine amlodipine (Velussi et al, 1996).In a meta-analysis of 100 controlled and uncontrolled trials, the relative effect of different antihypertensive agents on proteinuria and renal function was assessed in patients with diabetes (Kasiske et al, 1993). Treatments with ACE inhibitors, calcium antagonists, and beta blockers had a similar effect on mean arterial pressure. The greatest reductions in urine albumin excretion occurred in patients treated with ACE inhibitors. ACE inhibitors and CCBs appeared to have a more favorable effect on GFR compared with other antihypertensive agents. Multiple linear regression analysis indicated that only ACE inhibitors decreased proteinuria and had a favorable effect on GFR independent of blood pressure changes, i.e., greater than would have been expected if the mechanism for the improvement was limited to blood pressure reduction alone. However, a second meta-analysis suggested that at maximal antihypertensive doses, there was no significant difference between the antiproteinuric effects of ACE inhibitors and those of other antihypertensive drugs (Weidmann et al, 1995). Importantly, most of the published comparison studies were of short duration (only one year or less), and several were open-label and included only small numbers of patients or heterogeneous groups of type 1 and type 2 diabetic patients.Thus, whether the effects of ACE inhibitors on renal function in patients with diabetes are unique to this class of agent or represent a nonspecific effect of blood pressure reduction remains controversial. ACE inhibitors may reduce albumin excretion more than other agents in patients with type 2 diabetic nephropathy, but their effect on GFR may be similar (Lacourciere et al, 1993; Parving et al, 1996; Nielsen et al, 1997). Direct, long-term, double-blind, randomized comparison trials are needed to determine which is more important, the degree of blood pressure reduction or the class of antihypertensive agent used.*****ARBs vs placebo or no RXon renal function*******1. Hatsuk a szimptmk cskkentsre, a nehzlgzs, az dma mrsklsre, ill. megszntetsre, valamint a terhelsi kapacits nvelsre bizonytott (43-45.). Az, hogy az ACE-gtlk s a bta-blokkolk alkalmazsa diuretikumok nlkl legtbbszr keresztlvihetetlen, kzvetetten a diuretikumok kedvez tllsi hatsra utal (46-47).2. Diuretikumokat kell alkalmazni folyadkretencival jr szvelgtelensg valamennyi esetben. A folyadkretenci megszntetse, illetve visszatrsnek megelzse rendszerint csak diuretikumok adsval lehetsges. A diuretikumok mindig ACE-gtlkkal s bta-receptor blokkolkkal egytt kell alkalmazni, monoterpia nem javasolt.***