Kidneys and Hypertension

Dr. Shahrzad Shahidi

Nephrologist

Isfahan University of Medical sciences

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Hypertension (HTN)

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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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Adult Classification

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Classification Systolic BP (mmHg)

Diastolic BP (mmHg)

Normal Less than 120 and Less than 80

PreHTN 120-139 or 80-89

Stage 1 HTN 140-159 or 90-99

Stage 2 HTN > 160 or > 100

Chobanian AV, et al. Hypertension 2003;42(6):1206–1252

Classification for Adults

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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

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.

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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

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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.

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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.

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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.

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Secondary Hypertension

Renovascular DiseaseRenal parenchymal disease:

CKDGlomerulonephritisADPKDObstructive uropathy,…

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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

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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.

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Treatment - in Atheroslerotic RAS

Modify risk factors. Control BP with loop diretics, CCBs,

centrally acting agents, B blockers, Treatment by angioplasty & stenting

OR surgery.

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Indications for surgery Single kidney with stenosis. Bilateral RAS. Uncontrolled BP/ flash pulm edema. Rapidly deteriorating kidney

function. Meaningful nephron mass in the

kidneys.

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Fibromuscular dysplasia.

Otherwise healthy young women aged 15-50 yrs.

Angiography with “string of beads” pattern

Angioplasy is the treatment.

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Fibromuscular Dysplasia, before& after PTRA

Atherosclerotic RAS before & after stent

Safian & Textor. NEJM 344:6 18

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)

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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.

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Initial Evaluation

Previous drug treatment and side effects.

Contraindication to specific drugs.

Family history

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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

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

arterial disease.

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Treatment Goals

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Reduce morbidity & mortality Select drug therapy based on evidence

demonstrating risk reduction

Patient Population Target BPMost 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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Lifestyle Modifications

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Modification RecommendationApproximate Systolic BP Reduction (mm Hg)

Weight lossMaintain normal body weight

(BMI 18.5–24.9 kg/m2)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 persons2–4

DASH, Dietary Approaches to Stop Hypertension

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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.

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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

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Remember side effects

Hyperkalemia (ACE, ARB) Fluid retension (Amlodipine) Bradycardias (B blocker, Clonidine) Massive fluid overload & Tachycardia

(Minoxidil)

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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

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Antihypertensives - ACEIsBegin 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%

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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

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Selection of ACEIs vs ARBsCost of therapyPatient toleranceClinician preference

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Antihypertensives: ARBs

Nondihydropyridine CCBs

Diltiazem/verapamil decrease glomerular injury without negatively changing renal hemodynamics

May have beneficial effects on proteinuria similar to ACEIs

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Nondihydropyridine CCBs Studies suggest efficacy of

combination therapy with ACEIs & nondihydropyridine CCBs may be superior in proteinuria reduction than either agent alone

Generally 2nd line when ACEIs or ARBs not tolerated

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Speculations on JNC VIII

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Diuretics will remain first line therapy Chlorthalidone vs. HCTZ

Beta blockers will be dropped to 2nd or 3rd 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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