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MODULE 3 CHAPTER 2 B HYPERTENSION AND KIDNEY Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension.

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Presentation on theme: "MODULE 3 CHAPTER 2 B HYPERTENSION AND KIDNEY Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension."— Presentation transcript:

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2 MODULE 3 CHAPTER 2 B HYPERTENSION AND KIDNEY

3 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

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5 Projections for the Year 2010: Incident & Point-Prevalent ESRD Patients USRDS 2000 Annual Data Report. Bethesda, Md. 2000. 19841986198819901992199419961998200020022004200620082010 0 100 200 300 400 500 600 700 Incidence R 2 = 99.8% Point prevalence R 2 = 99.7% Projection Number of Patients 95% Confidence Interval 326,217 372,407 661,330 86,825 98,953 172,667 Number of Patients, thousands

6 Adjusted ESRD Incident Rates, by Primary Diagnosis and Diabetes in the General Population Incident ESRD patients; rates adjusted for age, gender, & race. Data on the prevalence of diabetes in the general population obtained from the CDC’s Behavioral Risk Factor Surveillance System. United States Renal Data System. 2003 Annual Data Report Graphics. Available at: http://www.usrds.org/slides.htm. Accessed 31 October 2003.http://www.usrds.org/slides.htm 350 300 200 100 0 8183858789919395979901 Rate per Million Population 50 150 250 Incident Rates in the ESRD Population Glomerulonephritis Cystic Kidney All Diabetes Hypertension 9 8 6 4 9192939495969798990001 5 7 90 Percent of Population Prevalence of Diabetes in the General Population

7 CVD Mortality Markedly Increased in ESRD Reprinted with permission from Foley RN et al. Am J Kidney Dis. 1998;32(supple 3):S112–S119. CVD mortality 10–20 times higher in ESRD than the general population 120 times higher for ESRD patients aged 25 to 34 Dialysis male Dialysis female Dialysis black Dialysis white GP male GP female GP black GP white Annual Mortality, % Age, years 25– 34 35– 44 45–5455– 64 65– 74 75– 84 >85 100 10 1 0. 1 0.0 1 GP = General population.

8 All-Cause Mortality in the General Medicare and Dialysis Populations (Pts. Age 65+) Deaths/1000 pt-yr at risk 400 350 300 250 200 150 100 50 0 Non-CKDCKDDialysis CVD No CVD

9 Prevention Prevent ESRD as well as CVD in hypertensives as ESRD patients most often die of cardiovascular disease

10 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

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18 The lesson Kidney is the culprit in the causation of hypertension even in the absence of hypertension So keep looking for hypertension in all kidney disease as well as in patients with family history of renal disease

19 2 nd issue: Hypertension predisposes as well as worsens kidney disease in established kidney disease patients

20 Hypertension is the leading cause of renal transplant

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24 Long-term Decline in GFR is Correlated With Poor Control of Blood Pressure: 9 Studies on Nephropathy Progression –14 –12 –10 –8–8 –6–6 –4–4 –2–2 0 959799 101103105 107 109111113115117119 MAP (mmHg) GFR (ml/min/yr.) (mmHg) Untreated HTN 140/90130/85 Graph: (Bakr is GL. J Clan Hyper tens. 1999) Trials: (Paring HH, et al. Br Med J. 1989) (Liberty GC, et al. JAMA. 1993) (Kaur S, et al. N Engle J Med. 1993*) (Herbert L, et al. Kidney Int. 1994) (Levitz H, et al. Kidney Int. 1994) (Moshi G, et al. N Engle J Med. 1996*) (Bakr is GL, et al. Kidney Int. 1996) (Bakr is GL, et al. Hypertension. 1997) (GISEN Group, Lancet. 1997) 121 *Trials marked by * are non-diabetic renal disease patients.

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26 The lesson Control of BP is very important in preventing future renal disease Control of BP is essential in further progression of renal disease So keep looking for early renal disease in hypertension

27 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage as well as CVD in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

28 Early Detection Albuminuria GFR/Creatinine clearance

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32 URINARY ALBUMIN EXCRETION alb:creat.(mg/mmol)overnight urine (ug/min) 24 hr urine collection(mg/24hrs) normalm:<3.5 f :<2.5 <20<30 microalbuminm:3.5-30 f : 2.5-30 20-20030-300 proteinuriam:>30 f : >30 >200>300

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35 The lesson In all hypertensives keep looking for micro albuminuria It predicts not only future renal disease but also cardiovascular disease

36 Early Detection Albuminuria GFR/Creatinine clearance

37 CVD Risk Factors  Hypertension*  Cigarette smoking  Obesity* (BMI >30 kg/m 2 )  Physical inactivity  Dyslipidemia*  Diabetes mellitus*  Micro albuminuria or estimated GFR <60 ml/min  Age (older than 55 for men, 65 for women)  Family history of premature CVD (men under age 55 or women under age 65) *Components of the metabolic syndrome.

38 Stages of Chronic Kidney Disease: NKF K/DOQI Classification CKD=chronic kidney disease, ESRD=end-stage renal disease, GFR=glomerular filtration rate, NKF K/DOQI=National Kidney Foundation Kidney Disease Outcomes Quality Initiative, RCN=radio contrast nephropathy Adapted from National Kidney Foundation. Am J Kidney Dis. 2002;39(2suppl 2):S1-S246. Stage I CKD risk factors/damage with preserved GFR Stage II Mild  kidney function Stage III Moderate  kidney function Stage IV Severe  kidney function Stage V Kidney failure, ESRD GFR (mL/min/1.73 m 2 ) 130906030150 Prevalence5.8%12.3%4.3%0.2%0.1% n (x1000)10,25921,7947,553363300  Risk of RCN, dialysis, and death

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40 Serum creatinine and GFR relationship Creatinine clearance

41 CKD AND CVD 15.8 33.1 57.3 71.2 0 10 20 30 40 50 60 70 80 Percent with CVD >9089-6059-30<30 Estimated GFR P<0.0001 for trend McCullough PA, et al for the KEEP Investigators. J Am Cull Cardio. 2005;45:424A.

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45 Estimation of eGFR,Creatinine clearance

46 To calculate visit this site and give necessary data http://www.medcalc.com/gfr.html

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48 The lesson Early detection of kidney disease is by albuminuria as well as eGFR, estimated cr.clearance Don’t rely upon solely on serum creatinine Even in the absence of proteinuria, calculate eGFR/Cr.clearance

49 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage as well as CVD in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

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53 KDIGO 2012 (CKD IN NON DIABETICS)

54 KDIGO 2012

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57 KDIGO 2013

58 Clinical Practice Guidelines for Management of Hypertension in CKD Type of Kidney DiseaseBlood Pressure Target (mm Hg) Preferred Agents for CKD, with or without Hypertension Other Agents to Reduce CVD Risk and Reach Blood Pressure Target Diabetic Kidney Disease <130/80 ACE inhibitor or ARB Diuretic preferred, then BB or CCB Nondiabetic Kidney Disease with Urine Total Protein-to-Creatinine Ratio  200 mg/g Nondiabetic Kidney Disease with Spot Urine Total Protein-to-Creatinine ratio <200 mg/g None preferred Diuretic preferred, then ACE inhibitor, ARB, BB or CCB Kidney Disease in Kidney Transplant Recipient CCB, diuretic, BB, ACE inhibitor, ARB

59 ACEI AND ARBS PREFERED DRUGS IN KIDNEY DISEASE STILL CERTAIN PRECAUTIONS HAVE TO BE OBSERVED

60 Afferent arteriole Efferent arteriole Angiotensin II and Renal Disease 1. Deficient auto regulation: Glomerulus 3. Abnormal matrix metabolism: 2. Increased efferent resistance: Bowman’s capsule High BP Constriction Increase in intra glomerular pressure

61 INTRAGLOMULAR HYPERTENSION AND HYPERFILTERATION ALTERATION IN PERMSELECTIVITY OF GLOMERULUS BASEMENT MEMBRANE THICKENING ALBUMINURIA TUBULO TOXICITY AND LOSS OF NEPHRONS HYPERFILTERATION IN REMAINING NEPHRONS RENAL INJURY HYPERTENSION

62 Efferent Arteriolar Dilation Glomerulus Decreased Filtration Less proteinuria Reduced blood pressure Decreased Glomerular Pressure Angiotensin II Role of Angiotensin II in Glomerular Function in Renal Failure RENAL FAILURE - TREATED Decrease in Afferent Arteriolar Blood Flow Blood Flow

63 Double edged weapon Although ACE I and ARB reduce albuminuria and retard progression of renal disease, decrease in GFR due to reduced intra glomerular pressure may result in worsening of renal function

64 General Concept A rise in serum creatinine of up to 30% of baseline ( given baseline up to 3 mg/dl) that remains stable in the absence of hyperkalemia ([K+] > 6) correlates with slower renal disease progression. Bakr is GL & Weir M Arch Intern Med. 2000:160:685-693 ©2006. American College of Physicians. All Rights Reserved.

65 severe cardiac failure

66 Which ACEI? Fosinopril and trandolapril are partially (in general, approximately 50%) excreted by the liver, such that the blood levels are less influenced by kidney failure than levels of other ACE-Is which are predominantly excreted by the kidneys.

67 Which ARB? Candesartan should not be used in renal disease Half-LifeBioavailabilityVolume of % Renal/Hepatic Drug(h)(%)Distribution Clearance Candesartan9150.13 L/kg60/40 Eprosartan51313 L30/70 Irbesartan11-1560-8053-93 L1/99 Losartan23334 L10/90 E-31746-9–12 L50/50 Olmesartan10-152817 L45/55 Telmisartan2442-58500 L1/99 Valsartan6  2517 L30/70

68 ACEIs and ARBs in Chronic Renal Failure Renal and Pharmacokinetic Differences Parameter ACEIs ARBs Proteinuria   Uric acid   * Glomerular filtration rate   Hyperkalemia   Dose titration suggestedYesNo BP reduction   Systemic accumulationYesNo AT 2 receptor stimulation  * Occurs only with losartan

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70 COOPERATE: UAER combination Reprinted with permission from Nakao N et al. Lancet. 2003;361:117–124. 0 1 2 3 0515203035 Trandolapril Losartan Combination Months After Randomization Median Urinary Protein Excretion, g/day Baseline 102540

71 COMBINATION – ACE I AND ARBS CAN BE COMBINED IN CHRONIC HEART FAILURE SHOULD BE AVOIDED IN AMI WITH HF SERIAL CHECK FOR CREATININE, POTTASIUM WATCH FOR HYPOTENSION SPIRANOLACTONE SHOULD BE AVOIDED WITH THIS COMBINATION –SHOULD BE USED WITH EITHER ONE OF THEM USEFUL TO REDUCE BP,FULL ANGIOTENSIN ANTAGONISM WITHOUT LOSING BRADYKININ ADVANTAGE, NEPHRO PROTECTION NOT USEFUL IN PATIENTS WITH PRESERVED EF

72 Safety of Calcium Channel Blockers Concern has been expressed in the past about the safety of CCBs with respect to both cardiac and renal outcomes The ALLHAT found amlodipine to be equivalent to chlorthalidone and Lisinopril in cardiac outcomes The IDNT in a randomized comparison found no beneficial or adverse impact of amlodipine (other than BP reduction) on renal outcomes or proteinuria The RENAAL in a secondary analysis found no beneficial or adverse impact on renal outcomes of use of any CCBs Should be used along with ACEI,ARB Effective BP reducing drugs

73 Cilnidipine Hypertension & Chronic Renal Insufficiency (CRI) Dual receptor blocker Cilnidipine dilates efferent arterioles leading to lowering of glomerular pressure EFFERENT ARTERIOLE DILATATION INTRA GLOMERULAR PRESSURE ALBUMINURIA

74 Cilnidipine Hypertension & Chronic Renal Insufficiency (CRI) 1 year study comparing benazepril with cilnidipine in hypertensive pts with benign nephrosclerosis – Proteinuria is a marker of renal insufficiency & improvement with drug therapy is desired 20 pts randomized to receive either – Benazepril – 5 to 10 mg/d – Cilnidipine – 10 to 20 mg/d Sr. creatinine & albuminuria were measured at 3 and 6 mth intervals resp. While Sr. creatinine levels did not change, cilnidipine like benazepril significantly reduced SBP, DBP & albuminuria Rose WG. Hypertens Res 2001;24:377-83

75 CNI, calcineurin inhibitor

76 CA BLOCKERS AND TRANSPLANT Calcium-channel blockers, particularly non- dihydropyridines, interfere with the metabolism and excretion of the calcinurine inhibitors (CNIs), cyclosporine and tacrolimus, as well as the mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus. This is relevant to the treatment of high BP in kidney- transplant recipients, but also in patients with immune- mediated CKD requiring immunosuppression. When such patients are prescribed non-dihydropyridine calcium-channel blockers, careful monitoring of CNIs and mTOR inhibitors blood levels is required if drugs or dosages are changed.

77 The Need for Sodium Restriction or Adequate Diuresis Most classes of antihypertensive agents lead, by compensation for lower BP, to sodium retention. This may substantially blunt the anti-hypertensive effect JNC 7 recommends that “most patients should receive a regimen including a thiazide type diuretic, either alone or with other agents.” This is particularly important in patients with high sodium intakes, in particular African-American patients. In African-Americans, adequate diuresis restores a responsiveness to RAAS blockers similar to that in Caucasians

78 Aldosterone antagonists All cases of LV dysfunction Sleep apnea Resistant hypertension When K is low in spite of acei/arb it can be used KEEP WATCHING FOR HYPERKALEMIA Eplerenone does not produce gynaecomatia

79 Renal failure Optimization :Always correct Volume overload Thiazide : Chlorthallidone 12.5-25mg/day if GFR >40ml/min/1.73 m2 Loop diuretics if GFR is less than this – Furosemide twice a day, Torsemide once a day Torsemide is preferred in renal failure Combination of diuretics : metallazone and loop diuretics in resistant fluid overload Optimize doses,timings,and combinations

80 Diuretics - combination YES – combine at different sites Loop diuretics + k sparing diuretics (amiloride, triamterene) Loop diuretics + Aldosterone inhibitors Loop diuretics + thiazide diuretics (metallazone) NO – don’t combine at same site 2 Loop diuretics 2 k sparing diuretics 2 thiazide diuretics

81 B BLOCKERS

82 B BLOCKERS IN RENAL DISEASE ALWAYS TO BE USED IF THERE IS CAD, HEART FAILURE,LV DYSFUNCTION AND TACHYARRHYTHMIA METOPROLOL, CARVEDILOL ARE PREFERED ATENOLOL BISOPROLOL NEBIVOLOL MAY BE AVIODED DOSAGE ADJUSTMENT ACCORDING HR AND BP

83 Alpha blockers Alpha-blockers reduce the symptoms of benign prostatic hyperplasia, which may be a co- morbidity to consider in older men with CKD. In general, alpha-blockers are not considered a first-line choice because of the common side effects of postural hypotension, tachycardia and headache. They should be commenced at a low dosage to avoid a first-dose hypotensive reaction. They do not require dosage modification

84 CENTRALLY ACTING DRUGS Doses of methyldopa or clonidine are not generally reduced in patients with impaired kidney function. Moxonidine is extensively excreted by the kidney and accordingly it has been recommended that the dosage (usually 200 to 400 mg daily) should be reduced in the presence of a low GFR. Clonidine is used in resistant hypertension with renal failure- can produce Brady if used with b blockers Abrupt withdrawal should be avoided Moxonidine is to be avoided in advanced heart failure

85 Direct vasodilators Hydralazine has little value in the management of chronically elevated BP in CKD, although it is sometimes used as a parenteral hypotensive agent. Minoxidil is generally used in patients with very resistant hypertension and thus may be helpful in patients with CKD. Because of the side effects of fluid retention and tachycardia, direct vasodilators (especially minoxidil) are usually combined with a beta- blocker and loop diuretic.

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88 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage as well as CVD in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

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92 Progression of Kidney Disease related to level of proteinuria and blood pressure lowering in MDRD Study Petersen. Annals of Internal Medicine. 1995

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96 NEPHROPATHY Lower levels of BP result in slower rates of decline in renal functions eg. someone 50 years of age with GFR of 50ml/mt and SBP of 144 will be on dialysis 8 years earlier than someone of the same age and GFR with SBP of 134

97 Kidney and Hypertension Kidney is the cause and effect of hypertension Kidney disease predisposes to hypertension and hypertension predisposes to kidney disease Early detection of kidney disease and treating it will prevent major kidney damage as well as CVD in future Similarly control of hypertension in established kidney disease will retard further progression Kidney is as important as heart and brain in hypertension management End Stage Renal Disease (ESRD) has to be prevented in Hypertension

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99 Conclusions Kidney initiates hypertension not only in secondary forms but also in essential hypertension Once hypertension sets in it further damages the kidney Associated kidney disease complicates the management as it requires careful selection as well as monitoring of therapy Nevertheless the identification early kidney disease in hypertension and early hypertension in kidney disease and proper management will retard the progression of not only kidney disease but also cardiovascular disease

100 END OF MODULE 3 CHAPTER 2B


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