Νεφροπάθεια και Υπέρταση σε ασθενή με ΣΔ Δημήτριος Β. Βλαχάκος Καθηγητής Παθολογίας - Νεφρολογίας Υπεύθυνος Νεφρολογικής Μονάδας Πανεπιστημιακό Γενικό Νοσοκομείο «ΑΤΤΙΚΟΝ»
1/3 of the population are obese 1/3 of obese people are diabetics
1/3 of diabetics develop CKD
Primary Diagnosis for Patients Who Start Dialysis Other Glomerulonephritis 10% 13% Diabetes 50.1% Hypertension 27%
Διαβητική Νεφροπάθεια Λευκωματουρία (0,5 γρ 24/ωρο) Διαβητική αμφιβληστροειδοπάθεια Απουσία κλινικών ή εργαστηριακών στοιχείων άλλης νεφρικής νόσου
Στοιχεία υπέρ μη Διαβητικής Νεφροπάθειας Παθολογικό ίζημα ούρων (αιματουρία, πυουρία, δύσμορφα ερυθρά, ερυθροκυτταρικοί κύλινδροι) Απουσία διαβητικής αμφιβληστροειδοπάθειας Ταχεία επιδείνωση πρωτεϊνουρίας Ταχεία άνοδος της κρεατινίνης του ορού Άτυπες υπερηχογραφικές αλλοιώσεις των νεφρών (ασυμμετρία του μεγέθους των νεφρών) Διάρκεια του ΣΔ τύπου 1 λιγότερο από 5 χρόνια
GFR (ml/min) Albuminuria (mg/24 h) Microalbuminuria Macroproteinuria 150 ΒΛΑΒΗ ΝΟΣΟΣ 5000 100 1000 50 0 200 Υ Π Ε Ρ Τ Α Σ Η 20 5 10 15 20 25 Years Strippoli et al. J Nephrol 2003;16:487 499
Smith MC and Dunn MJ, in Hypertension. Laragh JH and Brenner BM. Raven Press; 1995: 2081-2101. Prevalence of Hypertension In Chronic Renal Diseases Hypertension Prevalence (%) 80 70 60 50 40 30 20 10 0 MCN CIN IgA MGN APKD DN MPGN FSGN MCN=minimal change nephropathy CIN=chronic interstitial nephritis IgA=IgA nephropathy MGN=membranous glomerulonephritis APKD=adult-onset polycystic kidney disease DN=diabetic nephropathy MPGN=membranoproliferative glomerulonephritis FSGN=focal segmental glomerulonephritis
Hazard ratio (95% CI) ADVANCE = Action in Diabetes and Vascular disease: preterax and diamicron-mr Controlled Evaluation Ninomiya T, et al. J Am Soc Nephrol. 2009;20:1813 21. Albuminuria predicts renal events UACR predicted renal events in patients with 32.0 type 2 diabetes in the ADVANCE study 10,640 patients followed for 4.3 years 10-fold increase in baseline UACR 3.3-fold increase in risk of renal event 16.0 8.0 4.0 2.0 1.0 0.5 0.25 P for trend < 0.0001 10.5-fold increase in risk of renal event after correction for regression dilution 3 30 300 Microalbuminuria Baseline UACR (mg/g)
Lancet 2012
KI, suppl; 2011
Μικροαγγειοπάθεια
Συνολική επίπτωση % Συνολική επίπτωση % Διαβητική Νεφροπάθεια και ΣΔ Τύπου 1 Εντατικοποιημένη Συμβατική 5 0 4 0 Πρωτοπαθής πρόληψη 5 0 4 0 Δευτεροπαθής πρόληψη p 0.04 p 0.001 3 0 0 1 2 3 4 5 6 7 8 9 Χρόνια 3 0 0 1 2 3 4 5 6 7 8 9 Χρόνια DCCT. N Eng J Med 1993
Ασθενείς με συμβάματα (%) Μικροαγγειακές Επιπλοκές και Ρύθμιση Γλυκόζης 30 Συμβατική (1138) Εντατικοποιημένη (2729) p = 0.0099 20 10 0 0 3 6 9 12 15 Χρόνια UKPDS Study Group Lancet 1998;352:837
WKD 2010 Logo Protect your kidneys, Control Diabetes
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 -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.
Mechanism of action of RAAS blockers Normal Dilated afferent arteriole Diabetes CCB Constricted efferent arteriole (increased pressure) ACEIs/ARBs Proximal tubule Secretion of proteins (leakage) Proteins stored in cytoplasm cause cell activism and inflammation
ACE-I is More Renoprotective than Conventional Therapy in Type 1 Diabetes (Total N = 409) % with Doubling of Baseline Creatinine 0 25 50 75 Captopril Conventional therapy 100 Baseline creatinine > 1.5 mg/dl Decrease in Mean Blood Pressure (mm Hg) - 2 0-2 - 4-6 0 1 2 3 4 % Reduction in Proteinuria - 40-20 0-20 - 40 P <.001-8 NS - 60 Lewis et al. N Engl J Med. 1993;329:1456-1462. 2005. American College of Physicians. All Rights Reserved.
Subjects (%) Irbesartan in Diabetic Nephropathy Trial: Time to Doubling of Serum Creatinine, ESRD, or Death 70 60 50 40 30 20 10 0 0 6 12 18 24 30 36 42 48 54 Lewis EJ, et al. N Engl J Med. 2001;345:851-860. 1,715 Type 2 Diabetics with Nephropathy Irbesartan BP 140/77 Amlodipine BP 141/77 Placebo BP 144/80 RRR 23% P=.006 P=NS RRR 20% P=.02 Follow-up (mo) Percent Reduction 5 0-5 -10-15 -20-25 -30-35 Change in Proteinuria Irbesartan Amlodipine Placebo 60
IRMA 2: Αποτελέσματα Ομαλοποίηση της ταχύτητας απέκκρισης λευκωματίνης στα ούρα (UAE Rate) Ασθενείς (%) 45 40 35 30 25 20 15 10 5 0 21 Ομάδα ελέγχου (n=201) P=0.006 24 150 mg (n=195) 34 300 mg (n=194) Parving H-H, et al. N Engl J Med 2001;345:870-878.
CALM: ΜΕΙΩΣΗ UACR & ΔΑΠ ΜΕΤΑ ΑΠΟ ΘΕΡΑΠΕΙΑ 24 ΕΒΔΟΜΑΔΩΝ (mean 95% CI) 0-10 -20-30 -40-50 -60 UACR % candesartan cilexetil 16 mg OD n=42 lisinopril 20 mg OD n=43 p=0.04 candesartan cilexetil 16 mg OD + lisinopril 20 mg OD n=46 0-5 -10-15 -20 ΔΑΠ mmhg candesartan cilexetil 16 mg OD n=49 lisinopril 20 mg OD n=46 p<0.001 p<0.001 candesartan cilexetil 16 mg OD + lisinopril 20 mg OD n=49 Mogenson CE et al. BMJ 2000;321:1440-4.
ΣΥΝΔΙΑΣΜΕΝΗ ΘΕΡΑΠΕΙΑ ΜΕ ΑΜΕΑ & ΑRBs ΚΑΙ ΥΦΕΣΗ ΛΕΥΚΩΜΑΤΟΥΡΙΑΣ (MacKinnon M et al, Am J Kidney DIs 2007;48;8-20)
ONTARGET: Incidence of primary and secondary renal outcomes Outcome R, n (%) T, n (%) R + T, n (%) T vs R HR p R + T vs R HR p All dialysis, doubling of creatinine, death 1150 (13.4) 1147 (13.4) 1233 (14.5) 1.00 0.968 1.09 0.037 All dialysis and doubling of creatinine 174 (2.03) 189 (2.21) 212 (2.49) 1.09 0.420 1.24 0.038 R=ramipril T=telmisartan Mann JFE et al. Lancet 2008; 372:547-553.
The Role of the Renin-Angiotensin System in the Regulation of Erythropoiesis D. V. Vlahakos et al. Renal Hypoperfusion Am J Kidney Dis, April 2010 (Hypoxia) Renin Release Erythropoetin Secretion Angiotensinogen Angiotensin I Angiotensin II Aldosterone Salt and water retention Increased RBC Increased total blood volume Mass
American Journal of Kidney Disease
Προσαρμογή δόσης για έναρξη αμεα ή ARB σε XNN: Start low and go slow x1 x½ x¼ stop
Do not forget to instruct your patients on ACEi or ARB s and diuretics To report too much sweating, fever, diarrhea, or vomiting. To be sure to drink enough fluids to prevent dehydration. Before having surgery, to tell their doctor or dentist about all the products they use (including prescription drugs, nonprescription drugs, and herbal products). To avoid NSAIA s, potassium supplements or salt substitutes that contain potassium.
2013 ESH/ESC Guidelines for the management of arterial hypertension European Society of Hypertension European Society of Cardiology Journal of Hypertension 2013;31:1281-1357 Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Initiation of lifestyle changes and antihypertensive drug treatment Other risk factors, asymptomatic organ damage or disease High normal SBP 130 139 or DBP 85 89 Blood pressure (mmhg) Grade 1 HT SBP 140 159 or DBP 90 99 Grade 2 HT SBP 160 179 or DBP 100 109 Grade 3 HT SBP 180 or DBP 110 No other RF No BP intervention Lifestyle changes for several months Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 1 2 RF Lifestyle changes No BP intervention Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 3 RF Lifestyle changes No BP intervention Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 OD, CKD stage 3 or diabetes Lifestyle changes No BP intervention Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs Lifestyle changes No BP intervention Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure; HT, hypertension; OD, organ damage; RF, risk factor; SBP, systolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Blood pressure goals in hypertensive patients Recommendations SBP goal for most Patients at low moderate CV risk Patients with diabetes Consider with previous stroke or TIA Consider with CHD Consider with diabetic or non-diabetic CKD SBP goal for elderly Ages <80 years Initial SBP 160 mmhg SBP goal for fit elderly Aged <80 years SBP goal for elderly >80 years with SBP 160 mmhg DBP goal for most DBΡ goal for patients with diabetes <140 mmhg 140-150 mmhg <140 mmhg 140-150 mmhg <90 mmhg <85 mmhg SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Hypertension treatment for people with nephropathy Recommendations Additonal considerations Consider lowering SBP to <140 mmhg Consider SBP <130 mmhg with overt proteinuria RAS blockers more effective to reduce albuminuria than other agents Combination therapy usually required to reach BP goals Combination of two RAS blockers Aldosterone antagonist not recommended in CKD Monitor changes in egfr Indicated in presence of microalbuminuria or overt proteinuria Combine RAS blockers with other agents Not recommended Especially in combination with a RAS blocker Risk of excessive reduction in renal function, hyperkalemia SBP, systolic blood pressure; CKD, chronic kidney disease; egfr, estimated glomerular filtration rate; RAS, renin angiotensin system. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Preferred hypertension treatment in specific conditions Condition Asymptomatic organ damage LVH Asymptomatic atherosclerosis Microalbuminuria Renal dysfunction Clinical CV event Other Previous stroke Previous myocardial infarction Angina pectoris Heart failure Aortic aneurysm Atrial fibrillation, prevention Atrial fibrillation, ventricular rate control ESRD/proteinuria Peripheral artery disease ISH (elderly) Metabolic syndrome Diabetes mellitus Pregnancy Blacks Drug LVH ACE inhibitor, calcium antagonist, ARB Calcium antagonist, ACE inhibitor ACE inhibitor, ARB ACE inhibitor, ARB Any agent effectively lowering BP BB, ACE inhibitor, ARB BB, calcium antagonist Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists BB Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist BB, non-dihydropyridine calcium antagonist ACE inhibitor, ARB ACE inhibitor, calcium antagonist Diuretic, calcium antagonist ACE inhibitor, ARB, calcium antagonist ACE inhibitor, ARB Methyldopa, BB, calcium antagonist Diuretic, calcium antagonist ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BB, beta-blocker; BP, blood pressure; CV, cardiovascular; ESRD, end-stage renal disease; ISH, isolated systolic hypertension; LVH, left ventricular hypertrophy. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) Recommendation 4 In the population aged 18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP 140 mm Hg or DBP 90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion Grade E) Recommendation 8 In the population aged 18 years with CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate Recommendation Grade B) The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
CKD and diabetes are prevalent and costly Prevalence General Medicare: population 2007 (n = 26,313,160; mean age 75.5) Cost General Medicare: costs 2007 ($208.8 billion) Diabetes 24.8% CKD 9.8% CKD 27.6% CVD 49.4% Diabetes 38.7% CVD 82.0% Data from Medicare database, patients aged 65 years of age US Renal Data System. 2009 Annual Report.
Zinman et al. for the EMPA-REG OUTCOME Investigators. N Engl J Med 2015
SGLT-2 Inhibition
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