«Διαχείριση της Υπέρτασης σε ασθενείς με Χρόνια Νεφρική Νόσο»

«Διαλέξεις της Ομάδας Εργασίας για την Υπέρταση» «Διαχείριση της Υπέρτασης σε ασθενείς με Χρόνια Νεφρική Νόσο» Rigas G. Kalaitzidis MD, PhD, MSc Department of Nephrology University Hospital of Ioannina

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Αντιυπερτασική θεραπεία στους ασθενείς με ΧΝΝ Υπέρταση & ΧΝΝ Μηχανισμοί αύξησης της ΑΠ στη ΧΝΝ Κατηγορίες αντιϋπερτασικών φαρμάκων και ΧΝΝ Επίπεδα αρτηριακής πίεσης Should targeting Albuminuria Επισημάνσεις

Αντιυπερτασική θεραπεία στους ασθενείς με ΧΝΝ Υπέρταση & ΧΝΝ

Percentage of CKD in white and African American participants stratified by SBP and BMI Kalaitzidis et al, AJKD, May 2009

Kalaitzidis R and Bakris G Kidney. Int 2009;Nov:18:1-7

Μηχανισμοί αύξησης της ΑΠ στη ΧΝΝ

Μηχανισμοί αύξησης της ΑΠ στη ΧΝΝ Προυπάρχουσα ιδιοπαθής υπέρταση Αύξηση εξωκυτταρίου όγκου Διέγερση του συστήματος RAS Αύξηση της δραστηριότητας του συμπαθητικού Αύξηση των παραγόντων με δράση δακτυλίτιδας Προσταγλανδίνες/βραδυκινίνες Τροποποίηση των παραγώγων ενδοθηλίου (NO/ενδοθηλίνη) Αύξηση σωματικού βάρους Χορήγηση EPO Υπερπαραθυρεοειδισμός/ ενδοκυττάριου Ca/υπερασβεστιαιμία Επασβέστωση αρτηριακού δένδρου Δυσλειτουργία χρόνιου μοσχεύματος Πτωματικό μόσχευμα από δότη με ιστορικό υπέρτασης Κυκλοσπορίνη, Tarcolimus,χορήγηση ανασοκατασταλτικών και κορτικοστεροειδών

Heterogeneity of Mechanisms Underlying Hypertension Patient 1 Patient 2 Patient 3 Sympathetic Nervous System Renin-Angiotensin System Total Body Sodium B. Waeber, March 2007

kidney constitutes an important determinant of the hypertension

CKD Multiple Interactions among the Mechanisms Controlling BP Stress Central factors Carotid sinus Hypertension Baroreflex defects β CO Sustained PVR Adrenergic drive 1 2 High renin α All 4 PVR Diet Na+ kept Low renin 3 K + Na+ Ca 2+ Age Na + Ca 2+ Kaplan and Opie. Lancet 2006;367:168 76

Probability of all-cause survival according to calcification score. Comparison between curves was highly significant ( 2 =42.66, P<0.0001). Probability of all-cause survival according to calcification score Blacher, J. et al. Hypertension 2001;38:938-942 Copyright 2001 American Heart Association

Επιπλέον μεταβολικές διαταραχές στην ΧΝΝ που σχετιζονται με αυξημένη ΑΠ LVH που δεν εξηγείται από την υπέρταση Διάμεση μυοκαρδιακή ίνωση Μειωμένη μυοκαρδιακή αιμάτωση Λειτουργικές και δομικές αλλαγές αρτηριών μυοκαρδίου Διαταραχές του μεταβολισμού του μυοκαρδίου μειωμένη ανταπόκριση σε β-διεγέρτες, διαταραχή στην συγκέντρωση ενδοκυττάριου Ca+, μείωση νουκλεοτιδίων πλούσια σε ενέργεια, μεταβολικές διαταραχές oxidative stress

Stages of CKD & relationship to hypertension KDOQI Am J Kidney Dis 2004

Διαχείριση της Υπέρτασης Aντιυπερτασικά φάρμακα

2013 ESH/ESC Guidelines Choice of antihypertensive drugs Τα επίπεδα της ΑΠ είναι αυτά που προσδιορίζουν τον καρδιαγγειακό κίνδυνο και όχι η επιλογή του αντι υπερτασικού Τhe main benefits of antihypertensive treatment are due to lowering of BP per se and are largely independent of the drugs employed.

suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations. diuretics (including thiazides, chlorthalidone and indapamide) angiotensin converting enzyme (ACE) inhibitors angiotensin receptor blockers calcium antagonists beta-blockers ESH guidelines 2013, 5.2.2 page 1309

2017 High Blood Pressure Clinical Practice Guideline:

2013 ESH/ESC Guidelines Choice of antihypertensive drugs Σήμερα η αντιυπερτασική θεραπεία εξατομικεύεται λαμβάνοντας υπόψιν Καταστάσεις όπως Ηλικία Συν νοσηρότητα Οικονομία Συμμόρφωση CKD

Αντιϋπερτασικά φάρμακα και νεφρική αιμοδυναμική Φάρμακα RPF GFR Πρωτεϊνουρία Διουρητικά 10% 15% β-αποκλειστές 10% 15% = Ανταγωνιστές Ca ++ = = = αmea / ARBs = =

Number of antihypertensive medications required to achieve BP goals in major clinical trials over the past decade Κhosla N, Kalaitzidis R et al Med Clin North Am 2009

suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations. Angiotensin converting enzyme (ACE) inhibitors Angiotensin receptor blockers (ARBs) ESH guidelines 2013, 5.2.2 page 1309

TABLE 15. Drugs to be preferred in specific conditions

Eur Heart J 2012

There is no strong evidence that would suggest a preference for ACE Inhibitors versus ARBs. R Kalaitzidis & M Elisaf Int J Nephrol & Kidney Fail 2017 Προσαρμογή και σχηματική απεικόνιση από Thomopoulos C. et 1. C. Thomopoulos et al. J. Hypertension 2015;33 :195-211 al. (2015)

Νεφροπροστατευτικό αποτέλεσμα των α-μεα και ARB Οφείλεται: Ελάττωση της συστηματικής αρτηριακής πίεσης Ελάττωση της σπειραματικής τριχοειδικής πίεσης Ελάττωση της δραστηριότητας του ενδονεφρικού ΣΡΑ Ελάττωση των τροφικών και λοιπών δυσμενών δράσεων της ΑγγΙΙ Ελάττωση της πρωτεϊνουρίας

Mechanistic Rationale for RAS Blockade in Diabetic Renal Disease Dilation of Efferent Arteriole Only Afferent arteriole Glomerulus Bowman s capsule Efferent arteriole Glomerular pressure Albumin excretion rate Valentino VA et al. Arch Intern Med 1991;151:2367-2372.

H χρήση των αναστολέων της ρενίνης-αγγειοτασίνης-αλδοστερόνης (RAAS) για τη μείωση της αρτηριακής πίεσης, τη μείωση της πρωτεϊνουρίας Την επιβράδυνση της προοδευτικής απώλεια της νεφρικής λειτουργίας

Primary Composite End Point of a Doubling of the Serum Creatinine Level, End-Stage Renal Disease, or Death. Group 1 had a serum creatinine level of 1.5 to 3.0 mg per deciliter, and group 2 had a serum creatinine level of 3.1 to 5.0 mg per deciliter at baseline N Engl J Med 2006;354:131-40.

JAMA Intern Med. 2014;174(3):347-354.

Αναστολείς της ρενίνης ACEIs Αναστολείς της Αλδοστερόνης ARBs Συνδυασμοί φαρμάκων για την αναστολή του RAAS

VA-NEFRON-D The primary end point was the first occurrence of a change in the estimated GFR (a decline of 30 ml per minute per 1.73 m2 if the initial estimated GFR was 60 ml per minute per 1.73 m2 or a decline of 50% if the initial estimated GFR was <60 ml per minute per 1.73 m2), end-stage renal disease (ESRD), or death

Περινδροπρίλη Flack JM et al. Vasc Health Risk Manag. 2011;7:777-787, Song JC et al. Formulary. 2001;36:487-4991, Mallion JM et al, Journal of Cardiovascular Pharmacology 1998;32:673-678, Lacourcière Y et al. Am J Hypertens. 1995;8:1154-1159.

24h blood pressure reduction BP figures don t matter only at your office! Των υπερτασικών ασθενών που λαμβάνουν αγωγή και έχουν φυσιολογική αρτηριακή πίεση στο ιατρείο είναι αρρύθμιστοι κατά τη διάρκεια του 24ωρου 1 Συστολική ΑΠ 140 mm Hg 24ωρο προφίλ συστολικής ΑΠ ενός αρρύθμιστου υπερτασικού ασθενή 7 h ΜΕΡΑ 23 h ΝΥΧΤΑ Ένας ρυθμισμένος ασθενής 7 h 1- Franklin SS et al. Hypertension.2015;65:16-20. 2- Degaute JP et al. Hypertension 1991;19:199-210.

DIURETIC ACE /ARB CCB A calcium antagonist should be considered as an add-on therapy to the RAS blocker regimen

CCB Classification of Agents V binding site D binding site N binding site (Calcium channel blockers: classification, mechanism of action and indications, 2013)

CCB - Mechanism of Action CCB bind to specific receptor sites Μείωση ενδοκυττάριου Ca ++ μείωση των περιφερικών αγγειακών αντιστάσεων Αύξηση έκκρισης προσταγλανδινών και βραδυκινίνης (Calcium channel blockers: classification, mechanism of action and indications, 2013)

2013 ESH/ESC Guidelines Choice of antihypertensive drugs Calciun antagonist Some meta-analyses suggest that these agents may be slightly more effective in preventing stroke [284,394,421], In all trials in which the design permitted or prescribed the simultaneous use of diuretics, beta-blockers or ACE inhibitors [269,299,301, 423], calcium antagonists were not inferior to comparative therapies in preventing heart failure.

Λογική του συνδυασμού ανταγωνιστή Ca με αμεα ή ARB CCB Arteriodilation Peripheral edema Effective in low-renin patients Reduces cardiac ischemia BP ACE/ARB RAS blockade CHF and renal benefits ACE/ARB Venodilation Attenuates peripheral edema Effective in high-renin patients No effect on cardiac ischemia Synergistic BP reduction Complementary clinical benefits CCB RAS activation No renal or CHF benefits

The ASCOT-BPLA study (%) 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 Cardiovascular mortality Atenolol ± thiazide (No of events patients: 342) Amlodipine ± perindopril (No of events patients: 263) HR = 0.76 (0.65-0.90) - P=0.0010 0.0 1.0 2.0 3.0 4.0 5.0 years (mmhg) 180 160 140 120 100 80 60 Systolic and diastolic blood pressure 164.1 163.9 94.8 94.5 SBP DBP Mean difference 2.7 Mean difference 1.9 Atenolol ± thiazide Amlodipine ± perindopril 137.7 136.1 Baseline 0.5 1.0 1.5 2.0 2.5 3.0 3.5 41.0 4.5 5.0 5.5 Last visit 79.2 77.4 Number at risk Amlodipine ± Perindopril 9639 9544 9441 9322 9167 8078 Atenolol ± Thiazide 9618 9632 9415 9261 9085 7975 Adjustment for the mean difference in SBP (2.7 mmhg) explains only half of event reduction in ASCOT 45 Dahlöf et al. Lancet. 2005;366:895-906.

Cumulative event rate Kaplan Meier for primary endpoint ACEI / HCTZ CCB / ACEI 679 20% 552 p<0.001 Time to 1 st CV morbidity/mortality (days) HR (95% CI): 0.80 (0.72, 0.90) Jamson N Eng J Med 2009 359 2417

Progression of chronic kidney disease -48% Lancet 2010;375:1173-81

The percentage change in proteinuria among patients treated with dihydropiridine CAs or non dihydropiride CAs adjusted for change in SBP and DBP 5 0-5 -10-15 -20-25 -30 dihydropiridine CAs P<0.16 nondihydropiridine CAs P<0.15 % Δ in proteinuria adjusted for SBP % Δ in proteinuria adjusted for DBP Kalaitzidis et al Arch Med Sci 2009

Br J Clin Pharmacol 75(1):129-135. manidipine, compared to amlodipine showed a larger reduction in the urinary albumin excretion rate despite similar blood pressure reductions manidipine reduces, whereas amlodipine increases intraglomerular pressure resulting in their disparate effects on albuminuria Br J Clin Pharmacol 75(1):129-135

DIURETIC ACE /ARB CCB

ACEi/ARB - Hydrochlorothiazide Combination: Safety Advantages ACEi/ARB RAAS Aldosterone Serum Potassium + Hydrocholorothiazide Plasma volume and natriuresis RAAS Aldosterone Serum Potassium Serum potassium levels remain within normal limits

Diuretics Used to Treat Hypertension Thiazide and Thiazidelike Diuretics Loop Diuretics Potassium- Sparing Diuretics * Hydrochlorothiazid e BA (%) T ½ (hours) DOA (hours) 65 75 3.0 10.0 6 12 Chlorothiazide 30 50 15.0 25.0 6 12 Chlorthalidone 65 24.0 55.0 24 72 Bendroflumethiazi de 90 2.5 5.0 18 24 Indapamide 90 6.0 15.0 24 36 Metolazone 65 14 12 24 Bumetanide 80 90 0.3 1.5 4-6 Furosemide Torsemide 10 100 80 100 0.3 3.4 6-8 3.0 4.0 6-8 Amiloride 15-20 17.0 26.0 24 Triamterene 83 (55) * 3.0 (3.0) * 7-9 Spironolactone >90 1.5 15.0 48-72 Eplerenone 69 2.2 9.4 NA Reprinted from Brater DC. In: Principles of Pharmacology: Based Concepts and Clinical Applications. 1995:657-672, with permission from Springer Science and Business Media; Delyani JA, et al. Cardiovasc Drug Rev. 2001;19:185-200; Rosenberg J, et al. Cardiovasc Drug Ther. 2005;19:301-306; Sica DA. Congest Heart Fail. 2003;9:100-105.

Τα θειαζιδικά διουρητικά επιτυγχάνουν την διουρητική τους δράση μέσω της αναστολής του συνμεταφορεά Na+/Cl (στο άπω εσπειραμένο νεφρικό σωληνάριο GFR>40m/min

Thiazide and Thiazide-like Diuretics Thiazide and Thiazide-like Diuretics Used to Treat Hypertension BA (%) T ½ (hours) DOA (hours) Hydrochlorothiazide 65 75 3.0 10.0 6 12 Chlorothiazide 30 50 15.0 25.0 6 12 Chlorthalidone 65 24.0 55.0 24 72 Bendroflumethiazide 90 2.5 5.0 18 24 Indapamide 90 6.0 15.0 24 36 Metolazone 65 14 12 24 * Parentheses denote active metabolite. The half-life of one active metabolite, potassium canrenoate, is 15 h. BA = bioavailability; T ½ = half-life; DOA = duration of action: NA = unknown. Reprinted from Brater DC. In: Principles of Pharmacology: Based Concepts and Clinical Applications. 1995:657-672, with permission from Springer Science and Business Media; Delyani JA, et al. Cardiovasc Drug Rev. 2001;19:185-200; Rosenberg J, et al. Cardiovasc Drug Ther. 2005;19:301-306; Sica DA. Congest Heart Fail. 2003;9:100-105.

ΜΕΙΟΝΕΚΤΗΜΑΤΑ ΤΗΣ HCTZ Δοσοεξαρτώμενες μεταβολικές ανεπιθύμητες ενέργειες: Κ + γλυκόζης Δυσλιπιδαιμία ουρικού οξέος Σεξουαλική δυσλειτουργία Απουσία μελετών που να δείχνουν μείωση των συμβαμάτων Λιγότερο ισχυρό φάρμακο σε σύγκριση με τη χλωροθαλιδόνη η την ινδαπαμίδη

in the 10 publications that could be identified, wherein the 2 drugs were compared head-to-head in trials lasting 4 weeks. Indapamide, used as 2.5 mg tablets in all but 1 trial, provided a 54% greater reduction in systolic blood pressure, that is, 5.1 mm Hg (confidence interval, 8.7 to 1.6) than seen with hydrochlorothiazide in doses from 12.5 to 50 mg/d. Hypertension. 2015;65:983-984.

For systolic blood pressure, random effects, DerSimonian Laired metaanalysis comparing hydrochlorothiazide (HCTZ) and indapamide (INDAP). George C. Roush et al. Hypertension. 2015;65:1041-1046 Copyright American Heart Association, Inc. All

Σύσταση από τις Βρετανικές Κατευθυντήριες Οδηγίες National Clinical Guideline Centre UK. Hypertension the clinical management of primary hypertension in adults. August 2011. http://guidance.nice.org.uk/cg127.

2013 ESH/ESC Guidelines Choice of antihypertensive drugs Diuretics ACCOMPLISH) trial [414] that their association with an ACE inhibitor was less effective in reducing CV events than the association of the Same ACE inhibitor with a calcium antagonist. diuretics such as chlorthalidone or indapamide should be used in preference to conventional thiazide diuretics, such as hydrochlorothiazide [271]

Adverse effects of major diuretics

loop diuretics

Loop Diuretics Used to Treat Hypertension BA (%) T ½ (hours) DOA (hours) Bumetanide 80 90 0.3 1.5 4-6 Loop Diuretics Furosemide 10 100 0.3 3.4 6-8 Torsemide 80 100 3.0 4.0 6-8 * Parentheses denote active metabolite. The half-life of one active metabolite, potassium canrenoate, is 15 h. BA = bioavailability; T ½ = half-life; DOA = duration of action: NA = unknown. Reprinted from Brater DC. In: Principles of Pharmacology: Based Concepts and Clinical Applications. 1995:657-672, with permission from Springer Science and Business Media; Delyani JA, et al. Cardiovasc Drug Rev. 2001;19:185-200; Rosenberg J, et al. Cardiovasc Drug Ther. 2005;19:301-306; Sica DA. Congest Heart Fail. 2003;9:100-105.

Διουρητικά και GFR Sarafidis et al. Expert Opin Drug Saf 2010

Adverse effects of loop diuretics

potassium-sparing diuretics

Diuretics Used to Treat Hypertension BA (%) T ½ (hours) DOA (hours) Amiloride 15-20 17.0 26.0 24 Potassium- Sparing Diuretics Triamterene 83 (55) * 3.0 (3.0) * 7-9 Spironolactone >90 1.5 15.0 48-72 Eplerenone 69 2.2 9.4 NA * Parentheses denote active metabolite. The half-life of one active metabolite, potassium canrenoate, is 15 h. BA = bioavailability; T ½ = half-life; DOA = duration of action: NA = unknown. Reprinted from Brater DC. In: Principles of Pharmacology: Based Concepts and Clinical Applications. 1995:657-672, with permission from Springer Science and Business Media; Delyani JA, et al. Cardiovasc Drug Rev. 2001;19:185-200; Rosenberg J, et al. Cardiovasc Drug Ther. 2005;19:301-306; Sica DA. Congest Heart Fail. 2003;9:100-105.

TABLE 15. Drugs to be preferred in specific conditions

Οι ανταγωνιστές του υποδοχέα των αλατοκορτικοειδών (σπιρονολακτόνη και επλερενόνη) αναστέλλουν ανταγωνιστικά την σύνδεση της αλδοστερόνης στους υποδοχείς αλατοκορτικοειδώνi Clin J Am Soc Nephrol 9: 2147 2163, December, 2014

Adverse effects of major diuretics

Aldosterone Blockade in Diabetic Nephropathy with Proteinuria Mehdi et al, J Am Soc Nephrol 2009

Number of antihypertensive medications required to achieve BP goals in major clinical trials over the past decade Κhosla N, Kalaitzidis R et al Med Clin North Am 2009

patients that require a third medication to achieve control tend be have worse kidney function.

suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations. beta-blockers ESH guidelines 2013, 5.2.2 page 1309

Μηχανισμοί δράσης β-αποκλειστών Μείωση καρδιακής παροχής Μείωση έκκρισης ρενίνης ΑΙΙ Μείωση περιφερικών αγγειακών αντιστάσεων μέσω κεντρικής δράσης

2013 ESH/ESC Guidelines Choice of antihypertensive drugs β blockers the large meta-analysis by Law et al. has shown beta-blocker-initiated therapy to be (i) equally as effective as the other major classes of antihypertensive agents in preventing coronary outcomes and (ii) highly effective in preventing CV events in patients with a recent myocardial infarction and those with heart failure [284] when used in combination with diuretics, to facilitate new-onset diabetes in predisposed patients [402].

β-blockers are no longer recommended as first-line treatment for hypertension by the Joint National Council (JNC) of the USA and have been relegated to fourth- or even fifth-line choices by the National Institute of Clinical Excellence of the UK

Comparative routes of elimination of β-blockers.

sympathetic over-activity is part of CKD and contributes to the maintenance of hypertension and associated cardiac complications. Larger prospective trials are needed to determine whether the properties of the vasodilating β- blockers will translate into improved cardiovascularoutcomes in CKD. Until then, given the high prevalence of cardiovascular disease in people with CKD and mortality benefits observed for some β-blockers, there is clearly a need for their use in CKD patients. Kalaitzidis R et al Nephrol Dial Transplant 2009

Cice at all 2003 JACC :41;1436-44

Central Alpha-Adrenergic Agonists The most commonly used drug in this group is clonidine Other members of the class include guanfacine and methyldopa. The rationale for their use is to mitigate the increase in sympathetic activity Clonidine causes sedation, dry mouth, bradycardia, and can worsen depression Rigas G. Kalaitzidis and George L. Bakris, 2017

Vasodilators As fourth-line agents, minoxidil or hydralazine sometimes are required when other antihypertensive treatment with calcium antagonists, RAAS blockers, and diuretics has failed Vasodilator use is associated with reflex tachycardia that can worsen angina pectoris, and these vasodilators should always be combined with a beta-adrenergic blocker weight gain, increased hair growth, pericardial effusion Rigas G. Kalaitzidis and George L. Bakris, 2017

Επίπεδα αρτηριακής πίεσης

Summary of Guidelines/Position Papers for Goal Blood Pressure in People with Kidney Disease or Diabetes from Various Consensus Committees around the World Κhosla N, Kalaitzidis R et al Med Clin North Am 2009

GFR (ml/min/year) 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 0-2 -4-6 -8-10 GFR (ml/min/year) SBP (mm Hg) 130 134 138 142 146 150 154 170 180 0-2 -4-6 -8-10 -12-14 mmhg r = 0.69; P < 0.05 r = 0.43; P < 0.05 Untreated HTN Untreated HTN -12 130/85 140/90-14 Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996. Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996. Klahr S, et al. N Eng J. Med 1994. Bakris GL. Hypertension. 1997. Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997. Lebovitz H, et al. Kidney Int. 1994. Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661. Reprinted by permission, Harcourt Inc. Rigas G. Kalaitzidis and George L. Bakris, 2017

% Risk Reduction Lower Blood Pressure Goals for Cardiovascular and Renal Risk Reduction: Are They Defensible? AIPRI MDRD Hou Trial IDNT RENAAL SBP (mmhg) Rigas Kalaitzidis, and George L. Bakris, J Clin Hypertens May 2009

ESH ESC and JNC 7 Guidelines Recommendations for BP Goals JNC 7 1 ESH-ESC 2 Type of hypertension BP goal (mmhg) BP goal (mmhg) Uncomplicated <140/90 130 139/80 85 Complicated Diabetes mellitus <130/80 130 139/80 85 Kidney disease <130/80* 130 139/80 85 Other high risk (stroke, myocardial infarction) *Lower if proteinuria is >1 g/day <130/80 130 139/80 85 1. Chobanian et al. Hypertension 2003;42:1206 52 2. Mancia et al. Blood Pressure 2009;18:308 472. Mancia et al. J Hypertens 2009;27:2121 58

We agree with the 2011 KDIGO clinical practice guideline for management of blood pressure in chronic kidney disease that goal blood pressure depends upon the degree of proteinuria:

Επίπεδα ΑΠ σε υπερτασικούς ασθενείς με νεφρική βλάβη 2012 KDIGO clinical practice guidelines πρωτεϊνουρία < 500 mg/day BP < 140/90 mmhg πρωτεϊνουρία 500 mg/day BP < 130/80 mmhg 2012 KDIGO clinical practice guidelines

Figure 1.12 NHANES participants at target blood pressure, 1998-2012 Data Source: National Health and Nutrition Examination Survey (NHANES), 1988 1994, 1999-2004 & 2007 2012 participants aged 20 & older. Single-sample estimates of egfr & ACR; egfr calculated using the CKD-EPI equation. Figure represents all hypertensive participants including those who were at target blood pressure, probably due to medication. Abbreviations: ACR, urine albumin/creatinine ratio; CKD, chronic kidney disease; egfr, estimated glomerular filtration rate. Vol 1, CKD, Ch 1 94

Should targeting Albuminuria Be Part of Cardiovascular risk Reduction Paradigm? Whaley-Connell and Kalaitzidis R Cardiology Clinics 2010

Toward Regression of Chronic Kidney Disease GFR 105 90 75 60 45 30 15 0 Baseline Regression Preventing/arresting progression Retarding progression ESRD Time

The Kidney, Hypertension and remaining challenges Άμεση συσχέτιση μεταξύ του βαθμού της πρωτεϊνουρίας και εξέλιξης σε τελικό στάδιο ΧΝΝ Μείωση της πρωτεινουρίας >30%, μείωση του κινδύνου για ΑΜΚ κατά 39-72% (3-5έτη) Kosla & Kalaitzidis, 2009

Επισημάνσεις

1 Ωστόσο αμφισβητείται η γενίκευση της χρήση των αναστολέων RAAS σε όλο το φάσμα της ΧΝΝ Nephrol Dial Transplant (2015) 0: 1 3

Μη πρωτεινουρικές νεφροπάθειες ο αποκλεισμός του συστήματος RAS στους ηλικιωμένους ασθενείς με ΧΝΝ

Current guidelines for the use of angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease are based on evidence with limited relevance to most persons older than 70 years with this condition. Ann Intern Med. 2009 May 19;150(10):717-24

2 Εκτίμηση νεφρικής λειτουργίας σε υπερτασικό ασθενή που λαμβάνει αποκλειστή του άξονα Μια μικρή αύξηση (έως 20%) της κρεατινίνης του ορού μπορεί να συμβεί όταν χορηγείται αντιϋπερτασική θεραπείαιδιαίτερα αποκλειστές Ένδεια του όγκου συστήματος ρενίνης-αγγειοτασίνης Καρδιακή ανεπάρκεια (RAS) αλλά αυτό δεν πρέπει Χρήση να NSAIDS εκληφθεί ως ένδειξη προοδευτικής επιδείνωσης της νεφρικής λειτουργίας

Nitin Khosla, M.D., Rigas Kalaitzidis, M.D., and George L. Bakris, M.D.Chapter 4 Hypertensive Kidney Disease

Initial and long-term change in GFR in patients with Type-2 diabetes initially started on the ACE inhibitor, lisinopril.. Note as well, with better BP reduction, thegfr dropped more, initially in the study, but the overall rate of decline at 5 years was less in the group with better BP control, in spite of a greater initial fall. Bakris et al,arch Intern Med 2000 Κhosla N, Kalaitzidis R et al Med Clin North Am 2009

BMJ 2017;356:j791 doi: 10.1136/bmj.j791

A graduated increased risk of end stage renal disease, adverse cardiac outcomes, and death for each 10% increase in creatinine, even below the 30% threshold Cumulative mortality according to levels of creatinine increase after reninangiotensin system blockade BMJ 2017;356:j791 doi: 10.1136/bmj.j791

3 Patient education has been demonstrated to result in improved blood pressure control Ann Intern Med. 2006;145(3):165

Relative frequencies (percent) of patient adherence to AHT at baseline (ie, 6 months after index diagnosis) and during follow-up. Circulation. 2009;120:1598-1605

4 Dosage adjustment of hypertensive drugs in patients with reduced glomerular filtration rate Rigas G. Kalaitzidis and George L. Bakris, 2010 Handbook of Chronic Kidney Disease Managment

Rigas G. Kalaitzidis and George L. Bakris, 2017 In press

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