신장환자의혈압조절 나기영. Factors involved in the regulation of blood pressure

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1 신장환자의혈압조절 K/DOQI Clinical practice guidelines on Hypertension and Antihypertensive agents in CKD 나기영 Factors involved in the regulation of blood pressure

(Richard Bright, 1826) Identified renin in saline extracts of rabbit kidneys raised BP when

2 Renal function curve MAP (mmhg) Central role of kidney in hypertension Patients with bounding pulse and edema hardened, contracted kidneys & cardiac hypertrophy at autopsy (Richard Bright, 1826) Identified renin in saline extracts of rabbit kidneys raised BP when injected into another rabbit (Tigerstedt & Bergman, 1898) Two-kidney, one-clip model (Goldblatt, 1934)

Impaired pressure-natriuresis in human hypertension and all experimental models of hypertension Infusion of Na-, water-retainning hormones renal excretory function

3 Impaired pressure-natriuresis in human hypertension and all experimental models of hypertension Infusion of Na-, water-retainning hormones renal excretory function Antihypertensive drugs shift the pressure-natriuresis relationship back to control levels Hypertension follows a transplanted kidney Mutations altering blood pressure in humans

4 Human genetic mutations altering BP Defect Hypertension Hypotension BSC ROMK CLCNKB TSC Bartter syndrome Gitelman sydrome ENaC Liddle syndrome Recessive PHA I 11β-HSD2 AME MR HT exacerbated by pregnancy Dominant PHA I Aldosterone GRA Aldosterone synthetase deficiency DOC 17α- hydroxylase deficiency 21-hydroxylase deficiency 11β- hydroxylase deficiency BSC: bumetanide-sensitive Na-K-2Cl cotransporter, ROMK: ATP-sensitive K + channel, CLCNKB: Cl - channel, TSC: thiazide-sensitive Na-Cl cotransporter, ENaC: epithelial Na + channel, PHA: pseudohypoaldosteronism 11β-HSD2: 11β-hydroxysteroid dehydrogenase-2, AME: apparent mineralocorticoid excess, MR: mineralocorticoid receptor, GRA: glucocorticoid-remediable aldosteronism, DOC: deoxycorticosterone Altering net renal salt reabsorption (Lifton et al, Cell, 2001) Hypertension in Renal Disease Acute Acute Renal Failure: 40% (GN/vascular 73%, TIN 15%), PSGN: 80% Chronic kidney disease (CKD) Stage 3 to 5: 50-70% Chronic GN: 15-85% Hemodialysis patient: 50-80%

5 Mechanisms of Hypertension in Chronic Kidney Disease 1. Pre-existing essential hypertension 2. Extracellular fluid volume expansion 3. Renin-angiotensin aldosterone system stimuation 4. Increased sympathetic activity 5. Endogenous digitalis-like factors 6. Prostaglandins/bradykinins 7. Alteration in endothelium-derived factors (NO/endothelin) 8. Increased body-weight 9. Erythropoietin administration 10. PTH secretion / increased intracellular Ca/ hypercalcemia 11. Calcified arterial tree 12. Renal vascular disease and renal arterial stenosis 13. Chronic allograft dysfunction 14. Cadaver allografts, especially from a donor with a family history of HT 15. Cyclosporine, tacrolimus, other immunnosuppressive and corticosteroid therapy

6 Clinical Impacts of Hypertension Heart Left ventricular hypertrophy Angina or prior myocardial infarction Prior coronary revascularization Heart failure Brain Stroke or transient ischemic attack Chronic kidney disease Peripheral arterial disease Retinopathy

7 ESRD Due to Any Cause In 332,544 Men Screened for MRFIT Klag MJ et al. NEJM 1996 Comorbidities in Renal Disease Patients

CVD, in patients with or without hypertension Slow

8 Definition of CKD Stage of CKD GOALS OF ANTIHYPERTENSIVE THERAPY IN CKD Lower blood pressure Reduce the risk of CVD, in patients with or without hypertension Slow progression of kidney disease, in patients with or without hypertension

9 Recommendations for high-risk patients High-risk patients: target organ damage, clinical CV disease, ± diabetes, ± CKD Antihypertensive agents: ACE inhibitor, ARB (diabetic kidney disease, nondiabetic kidney disease with spot urine protein-to- Cr ratio 200 mg/g) Target BP: <130/80 mmhg, lower SBP goal for patients with spot urine protein-to-cr ratio mg/g EVALUATION OF PATIENTS WITH CKD OR HYPERTENSION Blood pressure should be measured at each health encounter. Initial evaluation should include the following elements : Description of CKD Type (diagnosis), level of GFR, and level of proteinuria Complications of decreased GFR Risk for progression of kidney disease Presence of clinical CVD and CVD risk factors Comorbid conditions Barriers to self-management, adherence to diet and other lifestyle modifications, adherence to pharmacological therapy Complications of pharmacological therapy

10 Laboratory measurements for ascertainment of CKD Measurements for ascertainment of CVD and CVD risk factors in CKD Interval for follow-up evaluation in CKD

11 Classification of CKD by diagnosis and prevalence among patients with kidney failure Risk factors associated with faster GFR decline

$Causes of acute decline in GFR in CKD Resistant (refractory) hypertension should be$ adhering to an adequate and appropriate three-drug regimen that includes a

adhering to an adequate and appropriate three-drug regimen that includes a

12 Causes of acute decline in GFR in CKD Resistant (refractory) hypertension should be considered if the blood pressure goal cannot be achieved in patients who are adhering to an adequate and appropriate three-drug regimen that includes a diuretic, with all three drugs prescribed in near-maximal doses. Causes of resistant hypertension

MEASUREMENT OF BLOOD PRESSURE IN ADULTS Casual blood pressure (CBP) CBP refers to a blood pressure measurement taken in the physician's office or clinic setting.

13 MEASUREMENT OF BLOOD PRESSURE IN ADULTS Casual blood pressure (CBP) CBP refers to a blood pressure measurement taken in the physician's office or clinic setting. for screening Self-measured blood pressure (SMBP) for maintenance and follow-up Ambulatory blood pressure monitoring (ABPM) for initial diagnosis and monitoring changes in treatment White coat hypertension (WCH) : CBP > 140 mmhg, mean BP by ABPM < 135/85 mmhg for wake period or < 135/80 mhg for full day. CKD patients may have alterations in circadian rhythm of blood pressure including a nondipping pattern of blood pressure and nocturnal (sleep) hypertension Dipping : mean wake SBP or DBP falls at least 10% during sleep Super-dipping : sleep-related BP reduction > 20-30%, associated with neurological sequelae Nondipping : blunted sleep-related fall in mean SBP or DBP (<10%) Reverse-dipping : sleep BP is equal or higher to awake values, high risk for end-organ damage Masked hypertension : normal office BP but elevations during ABPM, associated with endorgan damage SBP : better predictor of end-organ damage and events (CHD, CVD, HF, stroke, renal failure, mortality) Elevated pulse pressure : better marker of increased CV risk Special considerations for BP measurement in CKD patients

4 g/d (less than 100 mmol/d) should be recommended in most adults

14 DIETARY AND OTHER THERAPEUTIC LIFESTYLE CHANGES IN ADULTS Dietary sodium intake of less than 2.4 g/d (less than 100 mmol/d) should be recommended in most adults with CKD and hypertension. Dietary Approaches to Stop Hypertension (DASH) Diet Lifestyle modifications

15 PHARMACOLOGICAL THERAPY: DIABETIC KIDNEY DISEASE Target blood pressure in diabetic kidney disease should be <130/80 mm Hg. Patients with diabetic kidney disease, with or without hypertension, should be treated with an ACE inhibitor or an ARB. Multiple antihypertensive agents are usually required to reach target blood pressure ACE inhibitors and ARBs are effective in slowing the progression of kidney disease with microalbuminuria due to type 1 and type 2 diabetes. ACEI effective in slowing progression of CKD with macroalbuminuric type 1 diabetes (strong). ACEI effective in slowing progression of CKD with macroalbuminuric type 2 diabetes (weak). ARB effective in slowing progression of CKD with macroalbuminuric type 2 diabetes (strong). ARB effective in slowing progression of CKD with macroalbuminuric type 1 diabetes (weak). Diuretics may potentiate the beneficial effects of ACE inhibitors and ARBs in diabetic kidney disease.

16 ACE inhibitors, ARBs, and nondihydropyridine calcium-channel blockers have a greater antiproteinuric effect than other antihypertensive classes in diabetic kidney disease. Use of combinations of agents could also be considered in patients whose blood pressure is controlled using a single agent, but with persistent spot total protein-to-creatinine ratio >500 to 1,000 mg/d. Dihydropyridine calcium-channel blockers may likely be used safely in patients taking an ACE inhibitor or ARB dihydropyridine calcium-channel blockers should not be used in diabetic kidney disease in the absence of therapy with an ACE inhibitor or ARB, may likely be used safely in patients taking an ACE inhibitor or ARB. An SBP goal even lower than <130 mm Hg should be considered for patients with total protein to creatinine ratio >500 to 1,000 mg/g. Lowering of SBP levels to <110 mm Hg should be avoided.

PHARMACOLOGICAL THERAPY: NONDIABETIC KIDNEY DISEASE Nondiabetic kidney diseases include glomerular diseases other than diabetes, vascular diseases other than renal artery disease,

Glomerular diseases are characterized by higher levels of proteinuria than other diseases.

17 PHARMACOLOGICAL THERAPY: NONDIABETIC KIDNEY DISEASE Nondiabetic kidney diseases include glomerular diseases other than diabetes, vascular diseases other than renal artery disease, tubulointerstitial diseases, and cystic disease. Among these diseases, the level of proteinuria is useful for diagnosis and prognosis. Glomerular diseases are characterized by higher levels of proteinuria than other diseases. Higher levels of proteinuria are associated with faster progression of kidney disease and increased risk of CVD. Target blood pressure in nondiabetic kidney disease should be <130/80 mm Hg. Patients with nondiabetic kidney disease and spot urine total protein to creatinine ratio 200 mg/g, with or without hypertension, should be treated with an ACE inhibitor or ARB.

18 Multiple antihypertensive agents are usually required to reach target blood pressure. ACE inhibitors are more effective than other antihypertensive agents in slowing the progression of most nondiabetic kidney diseases (Strong). The beneficial effect is greater in patients with higher levels of proteinuria (strong). Threshold value : 0.5 g/day ARBs may be more effective than other antihypertensive agents in slowing the progression of nondiabetic kidney disease (weak) ACE inhibitors and ARBs in combination may be more effective than either alone in slowing the progression of nondiabetic kidney disease (weak) Diuretics may potentiate the beneficial effects of ACE inhibitors and ARBs in nondiabetic kidney disease. ACE inhibitors, ARBs, and nondihydropyridine calcium-channel blockers have a greater antiproteinuric effect than other antihypertensive classes in nondiabetic kidney disease. Dihydropyridine calcium-channel blockers are less effective than other agents in slowing the progression of nondiabetic kidney disease with proteinuria dihydropyridine calcium-channel blockers should not be used in nondiabetic kidney disease in the absence of therapy with an ACE inhibitor or ARB, may likely be used safely in patients taking an ACE inhibitor or ARB. A SBP goal of <130 mm Hg is more effective in slowing the progression of nondiabetic kidney disease in patients with proteinuria (Strong). An even lower blood pressure goal may be more effective in patients with proteinuria >500 to 1,000 mg/g (weak)

USE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN CKD ACE inhibitors and ARBs can be used safely in most patients with CKD.

20 USE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN CKD ACE inhibitors and ARBs can be used safely in most patients with CKD. ACE inhibitors and ARBs should be used at moderate to high doses, as used in clinical trials. ACE inhibitors and ARBs should be used as alternatives to each other, if the preferred class cannot be used. ACE inhibitors and ARBs can be used in combination to lower blood pressure or reduce proteinuria. Patients treated with ACE inhibitors or ARBs should be monitored for hypotension, decreased GFR, and hyperkalemia. Adverse effects of ACEIs and ARBs

21 Causes of hypotension in adults Detection and management of hypotension, according to baseline SBP Intervals for monitoring GFR according to baseline GFR Changes in management based on magnitude of early decrease in GFR

22 Prevention and management of hyperkalemia, according to baseline serum potassium Use of ACEIs and ARBs in women of childbearing age

23 USE OF DIURETICS IN CKD Diuretics are useful in the management of most patients with CKD. Reduce ECF volume Lower blood pressure Potentiate the effects of ACE inhibitors, ARBs, and other antihypertensive agents Reduce the risk of CVD in CKD Choice of diuretic agents depends on the level of GFR and need for reduction in ECF volume.

24 Most patients with CKD should be treated with a diuretic. Thiazide diuretics given once daily are recommended in patients with GFR 30 ml/min/1.73 m2 (CKD Stages 1-3) Loop diuretics given once or twice daily are recommended in patients with GFR <30 ml/min/1.73 m2 (CKD Stages 4-5) Loop diuretics given once or twice daily, in combination with thiazide diuretics, can be used for patients with ECF volume expansion and edema. Potassium-sparing diuretics should be used with caution: - In patients with GFR <30 ml/min/1.73 m2 (CKD Stages 4-5) - In patients receiving concomitant therapy with ACE inhibitors or ARBs - In patients with additional risk factors for hyperkalemia Unlike other thiazide diuretics, metolazone retains effectiveness at GFR below 30 ml/min/1.73 m 2. Metolazone (Zaroxylyn ) can be started at a dose of 2.5 to 5.0 mg daily and titrated to 10 to 20 mg daily. Once metolazone has effected a diuresis, it can typically be dosed as infrequently as two to three times a week because of its very long half-life.

HYPERTENSION IN CKD. LEENA ONGAJYOOTH, M.D., Dr.med RENAL UNIT SIRIRAJ HOSPITAL

HYPERTENSION IN CKD. LEENA ONGAJYOOTH, M.D., Dr.med RENAL UNIT SIRIRAJ HOSPITAL HYPERTENSION IN CKD LEENA ONGAJYOOTH, M.D., Dr.med RENAL UNIT SIRIRAJ HOSPITAL Stages in Progression of Chronic Kidney Disease and Therapeutic Strategies Complications Normal Increased risk Damage GFR