Μηχανισμοί Bλάβης Eνδοθηλίου και Mικρολευκωματινουρία Δημήτριος Βλαχάκος Επίκουρος Καθηγητής Νεφρολογίας Β Προπαιδευτική Παθολογική Κλινική Παν/μίου Αθηνών «Αττικό» Νοσοκομείο, Αθήνα
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;121:1244 1263.
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
Υπολογισμός νεφρικής καθάρσεως (ml/min) σύμφωνα με τους Cockcroft-Gault [140-ηλικία (έτη)] Χ [Βάρος (Kg)] [ 72 ή 85 ] Χ [Κρεατινίνη (mg%)] Άνδρες Γυναίκες
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 130 120 110 100 90 80 70 60 50 40 30 20 15 10 0 Glomerular filtration rate (ml/min/1.73m 2 ) National Kidney Foundation. Am J Kidney Dis 2002; 39(2 Suppl 1):S1 S266
Definitions of Microalbuminuria and Macroalbuminuria Parameter Normal Macroalbuminuria Microalbuminuria Urine AER (μg/min) < 20 20-200 >200 Urine AER (mg/24h) < 30 30-300 >300 Urine albumin/ Cr # ratio (mg/gm) < 30 30-300 >300 AER=Albumin excretion rate CR # =creatinine
ΥΠΕΡΤΑΣΗ ΠΡΩΤΕΪΝΟΥΡΙΑ ΝΕΦΡΙΚΗ ΑΝΕΠΑΡΚΕΙΑ
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=0.0099 Risk reduction 25% (95% CI: 7% to 40%) 0 3 6 9 12 15 Years from randomisation
Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics MAP (mmhg) 95 98 101 104 107 110 113 116 119 0 GFR (ml/min/year) -2-4 -6-8 -10-12 -14 130/85 140/90 r = 0.69; P < 0.05 Untreated HTN Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.
Eπίδραση της αναστολής MEA στη διαβητική νεφροπάθεια σε ΣΔ τύπου 1 40 Kαπτοπρίλη Eξέλιξη σε θάνατο, αιμοκάθαρση ήμεταμόσχευση(%) 30 20 10 Placebo * 0 0 1 2 3 4 Παρακολούθηση (Έτη) Collaborative Study Group * p = 0.006 vs placebo. Lewis EJ et al. N Engl J Med 1993;329:1456-1462.
IDNT - Χρόνος έως τον διπλασιασμό της κρεατινίνης του ορού Ασθενείς (%) 70 60 50 40 30 20 10 0 Irbesartan Aμλοδιπίνη p=ns Ομάδα ελέγχου 33% p=0.003 37% p<0.001 0 6 12 18 24 30 36 42 48 54 60 Lewis EJ et al. New Engl J Med 2001;345:851-860. Παρακολούθηση (μήνες)
IRMA 2: Αποτελέσματα Εμφάνιση πρωτεϊνουρίας Ασθενείς (%) 18 16 14 12 10 8 6 4 2 0 14.9 Ομάδα ελέγχου (n=201) RRR=39% P=0.08 Parving H-H, et al. N Engl J Med 2001;345:870-878. RRR=70% P<0.001 9.7 150 mg (n=195) Irbesartan 5.2 300 mg (n=194)
REIN 2 Study
Treatment of Patients with Kidney Disease < 1 gm Proteinuria >1gm Proteinuria BP treatment goal <130/80 <125/75 # drugs required ~2-3 ~3-4
Επιλεγμένη Βιβλιογραφία 1. Hofman A, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer s disease in the Rotterdam study. Lancet 1997;349:151 154. 2. Cooper ME. Pathogenesis, prevention and treatment of diabetic nephropathy. Lancet 1998;352:213 219. 3. Taylor AA. Pathophysiology of hypertension and endothelial dysfunction in patients with diabetes mellitus. Endocrinol Metabol Clin North Am 2001;30:983 997. 4. Erhardt LR. Endothelial dysfunction and cardiovascular disease: the promise of blocking the renin-angiotensin system. Int J Clin Pract 2003;57:211 218. 5. Weber M. The telmisartan Programme of Research to show Telmisartan End-organ protection (PROTECTION) Programme. J Hypertens 2003;21 (Suppl 6):S37 S46. 6. 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: http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm 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):973-995. 9. 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):646-661. 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):1857-1863. 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):1688-1693. 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):275-279.