1. Kidneys and Hypertension Dr. Shahrzad Shahidi Nephrologist Isfahan University of Medical sciences 1

2. Hypertension (HTN) 2 Persistent elevation of arterial blood pressure (BP) 31% of Americans have BP > 140/90 mmHg Most patients asymptomatic Single most preventable cause of premature death in developed countries. Chobanian AV, et al. Hypertension 2003;42(6):1206–1252

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4. Adult Classification 4 Classification Systolic BP (mmHg) Diastolic BP (mmHg) NormalLess than 120andLess than 80 PreHTN120-139or80-89 Stage 1 HTN140-159or90-99 Stage 2 HTN> 160or> 100 Chobanian AV, et al. Hypertension 2003;42(6):1206–1252

5. Classification for Adults 5 Classification based on average of > 2 properly measured seated BP measurements from > 2 clinical encounters If systolic & diastolic BP values give different classifications, classify by highest category Prehypertension: patients likely to develop hypertension

6. Pathogenesis. No one gene is responsible. Studies shows that several difft genes may have an effect on BP. RARE SINGLE GENE CAUSES OF HTN HAVE BEEN IDENTIFIED. 6

7. Single Gene Causes of HTN Glucocorticoid remediable aldosteronism Syndrome of minerelocorticoid excess Pheochromocytoma - may occur with MEN type 2, Von Hippel Lindau disease, Neurofibromatosis type 1 Liddle’s Syndrome 7

8. Renin angiotensin system Renin –secreted by the juxtaglomerular apparatus. It converts angiotensinogen (inactive) to angiotensin 1.It then converts to angiotensin 2 by ACE. Increased renin – RAS, Renal cell carcinoma & rarely some renin secreting tumours. 8

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10. Actions of angiotensin II Arteriolar vasoconstriction. Efferent arteriolar vasocnstriction. Aldosterone secretion. Epinephrine release (adrenaline). Smooth muscle hypertrophy. Inhibit renin release (negative feed back). Myocardial growth. 10

11. Other pathogenesis Arterial stiffness – Aging, DM, Kidney disease. Sympathetic nervous system- Activation associated with sudden rise in BP.- By increasing stroke volume, HR, systemic vascular resistance and activation of RAS. 11

12. Secondary Hypertension Renovascular Disease Renal parenchymal disease: CKD Glomerulonephritis ADPKD Obstructive uropathy,… 12

13. Renal artery stenosis Atherosclerotic or fibromuscular dysplasia as etiology Clinically difficult to control HTN Renal dysfuntion Resistant fluid retention Worsening Cr with ACEI or ARB 13

14. Investigations US Kidneys- assymmetry. Doppler of renal arteries. Captopril renogram - affected kidney may show a 30% decline in function. MRA. Angiogram- secure diagnosis & allow intervention. 14

15. Treatment - in Atheroslerotic RAS Modify risk factors. Control BP with loop diretics, CCBs, centrally acting agents, B blockers, Treatment by angioplasty & stenting OR surgery. 15

16. Indications for surgery Single kidney with stenosis. Bilateral RAS. Uncontrolled BP/ flash pulm edema. Rapidly deteriorating kidney function. Meaningful nephron mass in the kidneys. 16

17. Fibromuscular dysplasia. Otherwise healthy young women aged 15-50 yrs. Angiography with “string of beads” pattern Angioplasy is the treatment. 17

18. Fibromuscular Dysplasia, before & after PTRA Atherosclerotic RAS before & after stent Safian & Textor. NEJM 344:6 18

19. Initial assessment Duration of HTN Other CVD risk factors. Anything to suggest secondary HTN. (50<Age <30, sudden onset, presents as malignant HTN, sudden deterioration in BP control, resistant HTN) 19

20. Initial evaluation Other contributory factors like –drugs, overweight, Excess alcohol, excess salt intake, Lack of exercise, Environmental stress, smoking. Evidence of Complications- stroke, TIA, Carotid bruit, IHD, CHF, Cardiomegaly, PVD, Hypertensive retinopathy, Renal impairment, Proteinuria, Sexual dysfunction. 20

21. Initial Evaluation Previous drug treatment and side effects. Contraindication to specific drugs. Family history 21

22. Initial basic investigations Hematocrit FBS HDL, LDL (after 9-12 h fast) TG Cr K Ca Urinalysis ECG Optional tests: urinary albumin excretion or ACR 22

23. Target organ damage Heart- LVH, IHD, LVD,CHF. Brain- Stroke, TIA, Vasular dementia. Kidney- Chronic Kidney Disease. Eyes- Retinopathy. Peripheral Vasculature - Peripheral arterial disease. 23

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25. Treatment Goals 25 Reduce morbidity & mortality Select drug therapy based on evidence demonstrating risk reduction Patient PopulationTarget BP Most patients< 140/90 mmHg DM< 130/80 mmHg CKD<130/80 mmHg Chobanian AV, et al. Hypertension 2003;42(6):1206–1252

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27. Lifestyle Modifications 27 ModificationRecommendation Approximate Systolic BP Reduction (mm Hg) Weight loss Maintain normal body weight (BMI 18.5–24.9 kg/m 2 ) 5–20 per 10-kg weight loss DASH-type diet Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of fat 8–14 Reduced salt intake Reduce dietary Na intake to no more than 100 mmol per day (2.4 g Na or 6 g NaCl) 2–8 Physical activity Regular aerobic physical activity (at least 30 min/d, most days of the week)4–9 Moderation of alcohol intake Limit consumption to 2 drinks/d in men and 1 drink/d in women & lighter- weight persons 2–4 DASH, Dietary Approaches to Stop Hypertension

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31. What Drug in CKD In all proteinuric renal disease ACEI & ARB has a beneficial role. Dcreases intraglomerular pressure & thus reduce proteinuria. Dual blockade with ACEI & ARB is a useful combination. 31

32. In CKD Expect the need of 3 meds. First life style modification. If proteinuria ACEI or ARB. If fluid overload diuretics. If persistant proteinuria add ARB or ACEI. Last vascular smooth muscle relaxant: Minoxidil 32

33. Remember side effects Hyperkalemia (ACE, ARB) Fluid retension (Amlodipine) Bradycardias (B blocker, Clonidine) Massive fluid overload & Tachycardia (Minoxidil) 33

34. Antihypertensives - ACEIs No ACEI shown to be superior to any other ACEI 1˚ goal: treat BP to target 2˚ goal: control proteinuria ACEIs generally more cost-effective than ARBs Adverse effects with an ACEI; switch to an ARB may be appropriate 34

35. Antihypertensives - ACEIs Begin at a low dose; increase dose at 4-week intervals to reduce microalbuminuria (even normotensive patients) Antiproteinuric effects not necessarily attained at antihypertensive doses Increase dose until proteinuria reduced by 30-50% 35

36. Antihypertensives: ARBs ARBs have similar efficacy to ACEIs for kidney protection in patients with several forms of GN Proteinuria reduction: 25 to 47% Most clinicians use ACEI/ARB therapy in patients with nondiabetic CKD & proteinuria 36

37. Selection of ACEIs vs ARBs Cost of therapy Patient tolerance Clinician preference 37 Antihypertensives: ARBs

38. Nondihydropyridine CCBs Diltiazem/verapamil decrease glomerular injury without negatively changing renal hemodynamics May have beneficial effects on proteinuria similar to ACEIs 38

39. Nondihydropyridine CCBs Studies suggest efficacy of combination therapy with ACEIs & nondihydropyridine CCBs may be superior in proteinuria reduction than either agent alone Generally 2 nd line when ACEIs or ARBs not tolerated 39

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42. Speculations on JNC VIII 42 Diuretics will remain first line therapy Chlorthalidone vs. HCTZ Beta blockers will be dropped to 2 nd or 3 rd line therapy Combination RAAS inhibition may carry more risk than benefit and will probably not be recommended (some exceptions) Strong emphasis on combination therapy

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