Μηχανισμοί Bλάβης Eνδοθηλίου και Mικρολευκωματινουρία

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1 Μηχανισμοί Bλάβης Eνδοθηλίου και Mικρολευκωματινουρία Δημήτριος Βλαχάκος Επίκουρος Καθηγητής Νεφρολογίας Β Προπαιδευτική Παθολογική Κλινική Παν/μίου Αθηνών «Αττικό» Νοσοκομείο, Αθήνα

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4 Ventricular Dilation/ Cognitive Dysfunction Myocardial Infarction & Stroke Remodelling Macroproteinuria Congestive Heart Failure/ Secondary Stroke Atherosclerosis and LVH Microalbuminuria Endothelial Dysfunction Nephrotic Proteinuria End-Stage Renal Disease End-Stage Heart Disease/ Brain Damage and Dementia Risk factors Diabetes Hypertension Cardio/ Cerebrovascular Death Adapted from Dzau, Braunwald. Am Heart J 1991;121:

5 H έννοια της καθάρσεως Αρχή διατήρησης της μάζας C(ml/min) x Pcr (mg/dl) = V (ml/1440 min) x Ucr (mg/dl) C=(U*V)/P σε ml/min

6 Υπολογισμός νεφρικής καθάρσεως (ml/min) σύμφωνα με τους Cockcroft-Gault [140-ηλικία (έτη)] Χ [Βάρος (Kg)] [ 72 ή 85 ] Χ [Κρεατινίνη (mg%)] Άνδρες Γυναίκες

7 Stages of chronic renal disease TARGET ORGAN DAMAGE ASSOCIATED CLINICAL CONDITION Stage I Stage II Stage III Stage IV Stage V Kidney damage with normal or GFR Kidney damage with mild GFR Moderate GFR Severe GFR Kidney failure Glomerular filtration rate (ml/min/1.73m 2 ) National Kidney Foundation. Am J Kidney Dis 2002; 39(2 Suppl 1):S1 S266

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9 Definitions of Microalbuminuria and Macroalbuminuria Parameter Normal Macroalbuminuria Microalbuminuria Urine AER (μg/min) < >200 Urine AER (mg/24h) < >300 Urine albumin/ Cr # ratio (mg/gm) < >300 AER=Albumin excretion rate CR # =creatinine

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11 ΥΠΕΡΤΑΣΗ ΠΡΩΤΕΪΝΟΥΡΙΑ ΝΕΦΡΙΚΗ ΑΝΕΠΑΡΚΕΙΑ

12 Microvascular Endpoints (cumulative), UKPDS Renal failure or death, vitreous haemorrhage or photocoagulation 346 of 3867 patients (9%) % of patients with an event 30% 20% 10% 0% Conventional Intensive p= Risk reduction 25% (95% CI: 7% to 40%) Years from randomisation

13 Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics MAP (mmhg) GFR (ml/min/year) /85 140/90 r = 0.69; P < 0.05 Untreated HTN Bakris GL, et al. Am J Kidney Dis. 2000;36(3):

14 Eπίδραση της αναστολής MEA στη διαβητική νεφροπάθεια σε ΣΔ τύπου 1 40 Kαπτοπρίλη Eξέλιξη σε θάνατο, αιμοκάθαρση ήμεταμόσχευση(%) Placebo * Παρακολούθηση (Έτη) Collaborative Study Group * p = vs placebo. Lewis EJ et al. N Engl J Med 1993;329:

15 IDNT - Χρόνος έως τον διπλασιασμό της κρεατινίνης του ορού Ασθενείς (%) Irbesartan Aμλοδιπίνη p=ns Ομάδα ελέγχου 33% p= % p< Lewis EJ et al. New Engl J Med 2001;345: Παρακολούθηση (μήνες)

16 IRMA 2: Αποτελέσματα Εμφάνιση πρωτεϊνουρίας Ασθενείς (%) Ομάδα ελέγχου (n=201) RRR=39% P=0.08 Parving H-H, et al. N Engl J Med 2001;345: RRR=70% P< mg (n=195) Irbesartan mg (n=194)

17 REIN 2 Study

18 Treatment of Patients with Kidney Disease < 1 gm Proteinuria >1gm Proteinuria BP treatment goal <130/80 <125/75 # drugs required ~2-3 ~3-4

19 Επιλεγμένη Βιβλιογραφία 1. Hofman A, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer s disease in the Rotterdam study. Lancet 1997;349: Cooper ME. Pathogenesis, prevention and treatment of diabetic nephropathy. Lancet 1998;352: Taylor AA. Pathophysiology of hypertension and endothelial dysfunction in patients with diabetes mellitus. Endocrinol Metabol Clin North Am 2001;30: Erhardt LR. Endothelial dysfunction and cardiovascular disease: the promise of blocking the renin-angiotensin system. Int J Clin Pract 2003;57: Weber M. The telmisartan Programme of Research to show Telmisartan End-organ protection (PROTECTION) Programme. J Hypertens 2003;21 (Suppl 6):S37 S National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classfication, and stratification. Am J Kidney Dis 2002; 39(2 Suppl 1):S1 S266. Available from: 7. McCullough PA. Beyond serum creatinine: defining the patient with renal insufficiency and why? Rev Cardiovasc Med 2003;4(Suppl 1):S2 S6. 8. Bianchi S, Bigazzi R, Campese VM. Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications. Am J Kidney Dis. 1999;34(6): Keane WF. Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis. 2000;35(4suppl1):S97-S105. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3): Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal failure in proteinuric, non-diabetic nephropathy. The GISEN group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069): Herbert LA, Bain RP, Verme D, Cattran D, Whittier FC, Tolchin N, Rohde RD, Lewis EJ. Remission of nephrotic range proteinuria in type 1 diabetes. Collaborative Study Group. Kidney Int. 1994;46(6): Viberti G, Morgensen CE, Groop LC, Pauls JF. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994;271(4):