RENAL AND CARDIOVASCULAR INTERACTION

RENAL AND RENAL AND CARDIOVASCULAR CARDIOVASCULAR

INTERACTIONINTERACTION

Renal blood flowRenal blood flow

• Each kidney weights about 150 grs

• Blood flow is 400 ml /100gr /min

(20-25 % of cardiac output)

low oxygen extraction (about 8 %of the total body oxygen consumption)

CARDIOVASCULAR DISEASECARDIOVASCULAR DISEASE

• Renal hypoperfusion

• Prerenal azotemia

• Atheroembolism

• Septic embolism

• Immunologic phenomena

• Side effect of drugs

CHRONIC KIDNEY DISEASE

• Accelerates atherosclerosis• Hypertension • Heart failure• Pericardial effusion• Myocardial disease• Valvular disease • Cardiac arrhythmias • Sudden death• Dialysis related problems

CHRONIC KIDNEY DISEASE CHRONIC KIDNEY DISEASE

• eGFR of less than 60 ml/min/1.73 m2 for more than 3 months

• serum creatinine (Cr) greater than 1.5 mg/dl

• presence of kidney damage

• microalbuminuria at any level of eGFR

(random urine albumin-to-Cr ratio (ACR) of 30 to 300 mg/gm )

CHRONIC KIDNEY DISEASECHRONIC KIDNEY DISEASE

• JNC 7 has recognized CKD as an independent cardiovascular risk state

Decreasing levels of renal function act as a major adverse prognostic factor after a variety of cardiac events

Anemia and CKD

• WHO definition :Hb level less than 13 g/dl in men and less than 12 g/dl in women

• Anemia caused by CKD in 20 %of patients with stable CAD and 30 to 60 % of patients with HF

Anemia and CKD

• Relative deficiency of EPO causes:

impaired vascular repair, progression of atherosclerosis

Anemia and CKD

• Increased levels of:

• TNF-alpha

• ILs 1 and 6

• Endothelin

• Matrix metalloproteinases

directly reduce RBC production at the level of the bone marrow and further worsen the anemia

Anemia and CKD

• 28 of 29 large prospective studies of HF have found anemia to be an independent predictor of mortality.

• Among HF patients for each 1 g/dl decrement in Hb, there is a 13 % increase in risk for all-cause mortality

• Patients with anemia and CKD are more likely to progress to ESRD irrespective of their baseline level of renal function.

• As Hb drops over time, there is a graded increase in HF hospitalizations and death

EPO

• Increase in coronary flow reserve.

• Preventing endothelial cell apoptosis.

• Enhancing myocardial repair in myocardial injury that could minimize LV dysfunction by recruiting vascular progenitor cells, which can become functional myocardial cells, thereby increasing the contractile function of the injured ventricle.

Treatment of anemia with EPO

• Reducing morbidity, particularly that of cardiovascular origin

• Improving quality of life• Favorable changes in left ventricular

remodeling• Improved ejection fraction• Improved functional classification• Higher levels of peak O2 consumption with

exercise testing.


• Increased platelet activity, thrombin generation, and resultant increased risk of thrombosis

• Increased endothelin levels, increased asymmetric dimethylarginine, which theoretically reduces nitric oxide availability and results in HTN

• Worsened measures of oxidative stress.


• Two RCTs in CKD indicate that treatment with EPO to higher Hb targets resulted in higher CVD events.

• Until there is clear evidence that the partial correction of anemia has favorable outcomes in CVD, this form of treatment is not recommended for the primary purpose of improving the natural history of CVD.

ACCELERATION OF VASCULAR ACCELERATION OF VASCULAR CALCIFICATION CALCIFICATION

• Coronary artery calcification (CAC) seems to occur exclusively in atherosclerotic arteries and is absent in normal vessel walls.

• Patients with ESRD have the greatest absolute values and rates of accumulation of CAC.

• using CAC as a diagnostic or therapeutic target in patients with CKD or ESRD is not recommended.

RENAL DISEASE AND RENAL DISEASE AND HYPERTENSION HYPERTENSION

• An optimal BP can be defined as less than 120/80 (SBP being more important).

• Most patients with CKD and HTN require 3 or more antihypertensive agents to achieve a goal BP of less than 130/80 .

RENAL DISEASE AND RENAL DISEASE AND HYPERTENSIONHYPERTENSION

• Pharmacological therapy : RAAS antagonist often in combination with a thiazide-type diuretic.

• Dihydropyridine CCBs alone, cause relative afferent arteriolar dilation, increase intraglomerular pressure and worsen glomerular injury and thus should be avoided as singular agents for BP control.

Antihypertensive Agents in CKDAntihypertensive Agents in CKD

Type of Kidney Type of Kidney DiseaseDisease

Blood Blood Pressure Pressure Target Target

(mm Hg)(mm Hg)

Preferred Preferred Agents for Agents for CKD, With CKD, With (or Without) (or Without)

HypertensionHypertension

Other Agents to Other Agents to Reduce CVD Risk Reduce CVD Risk and Reach Blood and Reach Blood Pressure TargetPressure Target

Diabetic kidney Diabetic kidney diseasedisease

<130/80<130/80 BB ACE inhibitor or ACE inhibitor or ARBARB

AA(A)(A)

Diuretic preferred, Diuretic preferred, then BB or CCBthen BB or CCB

AA

Nondiabetic kidney Nondiabetic kidney disease with spot disease with spot urine total protein-urine total protein-to-creatinine ratioto-creatinine ratio 200 mg/g200 mg/g

<130/80<130/80 AA ACE inhibitor or ACE inhibitor or ARBARB

AA(C)(C)

Diuretic preferred, Diuretic preferred, then BB or CCBthen BB or CCB

AA

Nondiabetic kidney Nondiabetic kidney disease with spot disease with spot urine total protein-urine total protein-to-creatinine ratio to-creatinine ratio <200 mg/g<200 mg/g

<130/80<130/80 BB None preferredNone preferred Diuretic preferred, Diuretic preferred, then ACE then ACE

inhibitor, ARB, inhibitor, ARB, BB, or CCBBB, or CCB

AA

Kidney disease in Kidney disease in the transplant the transplant recipientrecipient

<130/80<130/80 BB None preferredNone preferred CCB, diuretic, BB, CCB, diuretic, BB, ACE inhibitor, ACE inhibitor,

ARBARB

BB

ACEI/ARBACEI/ARB in CKDCKD

• Elevation in Cr and ARF that are more likely when the patient is volume depleted or in the presence of occult bilateral renal artery stenosis or equivalent.

• Have SBP stable and greater than 90 mm Hg, euvolemia, and a drug regimen without concurrent renal toxic agents


• CKD patients enjoy an improved survival and reduced rates of ESRD on ACEI/ARB agents even though the serum Cr is chronically elevated on these agents because of reductions in intraglomerular pressure.

• Discontinuation of ACEI/ARB drugs because of moderate, asymptomatic rises in Cr is a common management error.


• Use ACEI or ARB in patients down to an eGFR of 15 ml/min/1.73 m2

• Below this level, case reports suggest a high rate of hyperkalemia and the concern of accelerating the course to ESRD and dialysis .

CONTRAST-INDUCEDCONTRAST-INDUCED NEPHROPATHYNEPHROPATHY

CONTRAST-INDUCEDCONTRAST-INDUCED NEPHROPATHYNEPHROPATHY

• A form of acute kidney injury

• definition: rise in serum Cr greater than 25 % or greater than 0.5 mg/dl from baseline after IV contrast administration

• frequency :13 % in nondiabetics and 20 % in diabetics undergoing PCI

is related in a curvilinear fashion to the eGFR

Contrast-Induced NephropathyContrast-Induced NephropathyDefinition

• New onset or exacerbation of renal dysfunction after contrast administration in the absence of other causes:

increase by > 25%

or

absolute of > 0.5 mg/dL

from baselinefrom baselineserum creatinineserum creatinine

Occurs 24 to 48 hrs post–contrast exposure, with creatinine Occurs 24 to 48 hrs post–contrast exposure, with creatinine peaking 5 to 7 days later and normalizing within peaking 5 to 7 days later and normalizing within

7 to 10 days in most cases 7 to 10 days in most cases

Occurs 24 to 48 hrs post–contrast exposure, with creatinine Occurs 24 to 48 hrs post–contrast exposure, with creatinine peaking 5 to 7 days later and normalizing within peaking 5 to 7 days later and normalizing within

7 to 10 days in most cases 7 to 10 days in most cases

Epidemiology

Incidence varies according to the population and risk factor profile.

Reports of incidence subject to under-reporting, due to lack of appropriate follow-up.

Incidence of 7% reported in the overall population exposed to radio-contrast agents. Incidence declining.

Incidence ≥50% in patients with multiple risk factors.

Prognostic Implications

3rd most common cause of hospital acquired renal insufficiency (11% of all cases). Behind pre-renal causes and nephrotoxic medications.

5.5 fold increase in mortality (in-hospital). < 1% risk of Hemodialysis. (19 % 2 yr survival) Associated with MI, TVR at 1 year; longer hospital

stay. Post-procedural creatinine more powerful predictor of

late events than CK-MB.

Prognostic Implications- Increased In-Hospital mortality.

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Levy EM, et al; Levy EM, et al; JAMAJAMA 1996;275(19):1489-94 1996;275(19):1489-94

Retrospective, 16,248 inpatients Cases with CIN

(n=183) matched with controls(n = 174). Adjusted co-morbidity

CIN: > 25% increase in baseline creatinine.

OR 5.5

PATHOPHYSIOLOGY

Pathophysiology of CIN Pathophysiology of CIN

• (1) direct toxicity of iodinated contrast material to nephrons related to the ionicity and osmolality of the contrast media.

• (2) microshowers of atheroemboli to the kidneys

• (3) contrast material– and atheroemboli-induced intrarenal vasoconstriction.

Pathophysiology of CINPathophysiology of CIN

• The most important predictor of CIN is underlying renal dysfunction.

Risk Stratification

Pre-existing renal impairment

Age Diabetes Heart failure Acute MI Cardiogenic shock Nephrotoxins Hypoalbuminemia Anemia Volume depletion

Procedural hypotension Intra-aortic balloon pump Cholesterol embolization Contrast volume and type

Patient related Procedural related

Risk Stratification- Risk score

0102030405060

0 or 1 2 3 4 5 6 7 or 8

Risk Score

% C

IN

0102030405060

0 or 1 2 3 4 5 6 7 or 8

Risk Score

% C

IN

Diabetes - any Tx

Age over 70

SVG treated

Multiple vessels treated

Female

IABP use

Acute coronary syndrome

CrCl < 50 cc/min

•9639 patients9639 patients•Multivariate predictors chosen by backward Multivariate predictors chosen by backward logistic regression with a entry/leave criteria of 0.1logistic regression with a entry/leave criteria of 0.1

Mehran et al, Mehran et al, JACC 2004JACC 2004

CIN PREVENTIONCIN PREVENTION

PREVENTION OF CONTRAST-PREVENTION OF CONTRAST-INDUCED NEPHROPATHY INDUCED NEPHROPATHY

• CIN must be discussed in detail during the informed consent process of high-risk patients before use of intravascular iodinated contrast.

Basic concepts in CIN Basic concepts in CIN prevention prevention

• (1) hydration and volume expansion

• (2) choice and quantity of contrast material

• (3) pre-, intra-, and postprocedural end-organ protection with pharmacotherapy

• (4) postprocedural monitoring and expectant care.

CIN Prevention TrialsAgent Design Results

Furosemide Pro-Ran Worsened CIN

Mannitol Pro-Ran Worsened CIN

Hydration with 1/2 NS Pro-Ran Benefit vs. furosemide & mannitol

Atrial natriuretic peptide Pro-Ran No benefit

Dopamine Pro No benefit

Endothelin antagonist Pro-Ran No benefit

Adenosine antagonist Pro-Ran No benefit

Calcium channel blockade Pro Not adequately studied

Low Osmolar contrast Pro-Ran Nonionic monomer= Nonionic dimer

Low vs. High Osmolar

n-Acetylcysteine

Fenoldopam

Sodium Bicarbonate

Pro-Ran

Pro-Ran

Pro-Ran

Pro-Ran

Low Osmolar CONTRAST Beneficial

?Benefit (low volume I.V. contrast)

No benefit

?Benefit

HYDRATION

HydrationHydration

Hydration

• Normal saline or isotonic sodium bicarbonate is reasonable

• Starting 3 to 12 hours before the procedure at a rate of 1 to 2 ml/kg/hr

• In those at risk, at least 300 to 500 ml of IV hydration before the contrast material is administered

• The postprocedural hydration target is a urine output of 150 ml/hr.

Prevention of CIN with Prevention of CIN with Sodium BicarbonateSodium Bicarbonate

Merten GJ et al. JAMA, 2004;291:2328-2334Merten GJ et al. JAMA, 2004;291:2328-2334

Patients With Baseline Serum Creatinine 1 to 8 mg/dlPatients With Baseline Serum Creatinine 1 to 8 mg/dlwho Underwent Contrast Exposure (Iopamidol in All) who Underwent Contrast Exposure (Iopamidol in All)

N=137N=137

Patients With Baseline Serum Creatinine 1 to 8 mg/dlPatients With Baseline Serum Creatinine 1 to 8 mg/dlwho Underwent Contrast Exposure (Iopamidol in All) who Underwent Contrast Exposure (Iopamidol in All)

N=137N=137

Sodium Chloride Sodium Chloride Hydration (154 mEq/L of Hydration (154 mEq/L of

Sodium Chloride)Sodium Chloride)N=68N=68

Sodium Chloride Sodium Chloride Hydration (154 mEq/L of Hydration (154 mEq/L of

Sodium Chloride)Sodium Chloride)N=68N=68

Sodium Bicarbonate Sodium Bicarbonate Hydration (154 mEq/L of Hydration (154 mEq/L of

Sodium Bicarbonate)Sodium Bicarbonate)N=69N=69

Sodium Bicarbonate Sodium Bicarbonate Hydration (154 mEq/L of Hydration (154 mEq/L of

Sodium Bicarbonate)Sodium Bicarbonate)N=69N=69

Primary endpoint: increase in serum creatinine ≥25% Primary endpoint: increase in serum creatinine ≥25% within 2 days post-exposurewithin 2 days post-exposure

Primary endpoint: increase in serum creatinine ≥25% Primary endpoint: increase in serum creatinine ≥25% within 2 days post-exposurewithin 2 days post-exposure

Endpoints

Sodium

Chloride

N=59

Sodium Bicarbonate

N=60P value

Incidence of CIN (%) 13.6% 1.7% 0.02

Incidence of CIN (↑SCr 0.5 mg/dL)

11.9% 1.7% 0.03

Merten GJ et al. JAMA, 2004;291:2328-2334Merten GJ et al. JAMA, 2004;291:2328-2334

Prevention of CIN with Prevention of CIN with Sodium Bicarbonate: ResultsSodium Bicarbonate: Results

Iodinated contrast agentsIodinated contrast agents

Name Osmolality Ionicity Viscosity

Diatrizoate

(renografin)

High

1940

Ionic 14

Ioxaglate Low

600

Ionic 15

Iohexol

(omnipaque)

Low

844

Nonionic 10-20

Iodixinol

(Visipaque)

Iso-osmolar

290

Nonionic 26

Iodinated contrast agents Iodinated contrast agents

• lowest rates of CIN with nonionic, iso-osmolar iodixanol (visipaque)

• Iodixanol(290 mOsm/kg) is less nephrotoxic than LOCM agents with osmolalities ranging from 600 to 800 mOsm/kg in the volumes of contrast used in trials.

• Iodixanol is the contrast agent of choice in patients at high renal risk undergoing PCI

Iodinated contrast agentsIodinated contrast agents

• The lower the eGFR, the smaller the amount of contrast

• Less than 30 ml for a diagnostic and less than 100 ml for interventional procedure

• More than 10 days between the 1st and 2nd contrast exposures if CIN has occurred with the 1st procedure.

Prevention- Contrast: LOCM vs. HOCM

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Meta-analysis:

39 trials, n= 5146 CIN > 0.5 mg/dl Overall: 7% CIN

Barrett and Carlisle J Am Soc NephrolBarrett and Carlisle J Am Soc Nephrol 92.92.

Prevention- Contrast: IOCM vs. LOCM

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All patients CKD CKD+DM

IOCM

LOCMP<0.001

P=0.001

P=0.003

% C

IN

Meta-analysis:

16 trials, n= 2727

SCr≥ .50 mg/dl

McCullough et al, JACC 2006McCullough et al, JACC 2006

PHARMACOTHERAPY

N-ACETYLCYSTEINE (NAC)


• metabolite of the sulfur-containing amino acid, Cysteine.

• Is produced within the human body. • Increases Glutathione Levels (acts as a

powerful antioxidant in the body )• Glutathione also detoxifies chemicals into

less harmful compounds. • Protects the body from acetaminophen

toxicity


• Heavy metals like lead, mercury, and arsenic are detoxified and removed from the body by N-Acetyl Cysteine

• may reduce the risk of colon cancer

N-acetylcysteineN-acetylcysteine

• standard dose : 600 mg IV bolus before and 600 mg P.O BID for the 48 hours after angioplasty

• double dose : 1200 mg IV bolus and 1200 mg P.O BID for the 48 hours after intervention

Postprocedural monitoring Postprocedural monitoring

1-High-risk hospitalized:

• Hydration 12 hours before the procedure and continued at least 6 hours afterward

• A serum Cr should be measured 24 hours after the procedure

Postprocedural monitoringPostprocedural monitoring

2-Outpatients, particularly with eGFR < 60 ml/min/1.73 m2:

• overnight stay or discharge to home with 48-hour follow-up and Cr measurement is advised.

Postprocedural monitoringPostprocedural monitoring

3-Those with eGFR < 30 ml/min/1.73 m2:

• - The possibility of dialysis

• - Preprocedural nephrology consultation

CIN prevention strategy

• 1-Hydration

• 2-Use of iodixanol (Visipaque)

• 3-Prophylactic NAC

is a reasonable three-pronged approach to minimize CIN and the risk of acute renal failure requiring dialysis in patients at risk.

PREVENTION

ROTATIONAL CORONARY ANGIOGRAPHY

• CAD is a 3-D disease process

• Single-plane acquisition requires multiple injections of contrast at multiple fixed angle.

• Digital flat panel technology provides larger field of vision and keeps all anatomy on the screen.

INNOVA SPIN TECHNOLOGY

INNOVA SPIN TECHNOLOGY(GE Medical Systems)

ROTATIONAL ANGIOGRAPHY

Specific DA-1 Agonism: Specific DA-1 Agonism: Fenoldopam Fenoldopam

A New Renal and Systemic Vasodilator

The CONTRAST TrialAlgorithmAlgorithm

Primary endpointPrimary endpointWorsening renal insufficiency within 12-96 hoursWorsening renal insufficiency within 12-96 hours

FenoldopamFenoldopam

Matching placeboMatching placebo

RandomizeRandomize

HydrateHydrate

1º prior to and 12 º after cath1º prior to and 12 º after cath

300 patients300 patientsat increased risk for contrast nephropathy undergoing PCIat increased risk for contrast nephropathy undergoing PCI

Prevention- Medical therapies

Positive results Neutral results Negative results

Theophylline N-acetylcysteine Furosemide

Statins Fenoldopam Mannitol

Ascorbic acid Calcium channel blockers

Endothelin receptor antagonist

Prostaglandins E1 ANP, L-Arginine

CIN Consensus Working Panel, AJC 2006

Evolution of National Kidney Foundation Evolution of National Kidney Foundation Guidelines on Hypertension and Guidelines on Hypertension and Antihypertensive Agents in CKDAntihypertensive Agents in CKD

NKF Task Force on CVD (1998)NKF Task Force on CVD (1998)Target Population:Target Population: Women with Cr Women with Cr 1.2 mg/dL, men with Cr 1.2 mg/dL, men with Cr 1.4 mg/dL, patients 1.4 mg/dL, patients

with protenuria, patients with kidney failure treated with hemodialysis, with protenuria, patients with kidney failure treated with hemodialysis, pertiioneal dialysis, or kidney transplantationpertiioneal dialysis, or kidney transplantation

Recommendations:Recommendations: Use JNC 6 Guidelines, but consider patients to Use JNC 6 Guidelines, but consider patients to be at highest CVD riskbe at highest CVD risk

NKF Task Force on CVD (1998)NKF Task Force on CVD (1998)Target Population:Target Population: Women with Cr Women with Cr 1.2 mg/dL, men with Cr 1.2 mg/dL, men with Cr 1.4 mg/dL, patients 1.4 mg/dL, patients

with protenuria, patients with kidney failure treated with hemodialysis, with protenuria, patients with kidney failure treated with hemodialysis, pertiioneal dialysis, or kidney transplantationpertiioneal dialysis, or kidney transplantation

Recommendations:Recommendations: Use JNC 6 Guidelines, but consider patients to Use JNC 6 Guidelines, but consider patients to be at highest CVD riskbe at highest CVD risk

K/DOQI Guidelines on CKD (2002)K/DOQI Guidelines on CKD (2002)Target Population:Target Population: At least 3 months of either: At least 3 months of either:

1) structural or functional abnormalities of the kidney, or 2) GFR <60 mL/min/1.73 m1) structural or functional abnormalities of the kidney, or 2) GFR <60 mL/min/1.73 m22

Recommendations:Recommendations: Consider patients to be at highest CVD risk. Treat risk factors Consider patients to be at highest CVD risk. Treat risk factors

K/DOQI Guidelines on CKD (2002)K/DOQI Guidelines on CKD (2002)Target Population:Target Population: At least 3 months of either: At least 3 months of either:

1) structural or functional abnormalities of the kidney, or 2) GFR <60 mL/min/1.73 m1) structural or functional abnormalities of the kidney, or 2) GFR <60 mL/min/1.73 m22

Recommendations:Recommendations: Consider patients to be at highest CVD risk. Treat risk factors Consider patients to be at highest CVD risk. Treat risk factors

K/DOQI Guidelines on Hypertension and Antihypertensive Agents (2004)K/DOQI Guidelines on Hypertension and Antihypertensive Agents (2004)Target Population:Target Population: CKD stages 1-4 (as defined by the K/DOQI Guidelines on CKD) CKD stages 1-4 (as defined by the K/DOQI Guidelines on CKD)Recommendations:Recommendations: Lifestyle modifications, blood pressure target <130/60 mm Hg, Lifestyle modifications, blood pressure target <130/60 mm Hg,

and antihypertensive agents specific for type of CKDand antihypertensive agents specific for type of CKD

K/DOQI Guidelines on Hypertension and Antihypertensive Agents (2004)K/DOQI Guidelines on Hypertension and Antihypertensive Agents (2004)Target Population:Target Population: CKD stages 1-4 (as defined by the K/DOQI Guidelines on CKD) CKD stages 1-4 (as defined by the K/DOQI Guidelines on CKD)Recommendations:Recommendations: Lifestyle modifications, blood pressure target <130/60 mm Hg, Lifestyle modifications, blood pressure target <130/60 mm Hg,

and antihypertensive agents specific for type of CKDand antihypertensive agents specific for type of CKD

Evaluation and Management of HTN and Evaluation and Management of HTN and Use of Antihypertensive Agents in CKDUse of Antihypertensive Agents in CKD

Evaluation of the patient with CKDEvaluation of the patient with CKD

Monitor response, manage side effectsMonitor response,

manage side effects

Introduce or increaseACEI or ARB


Introduce or increasediuretic or other agentIntroduce or increasediuretic or other agent

Periodicallyre-evaluatePeriodicallyre-evaluate

Is BP <130/60 mm Hg?

Is BP <130/60 mm Hg?

Can an ACEI or ARB be introduced

or ↑

Can an ACEI or ARB be introduced

or ↑

Diabetic kidney disease? OR

Nondiabetic kidney disease with urine total protein-to-creatinine

ratio 200 mg/g?

Diabetic kidney disease? OR

Nondiabetic kidney disease with urine total protein-to-creatinine

ratio 200 mg/g?YesYes

YesYes NoNo

YesYes

NoNo

National Kidney Foundation. Am J Kidney Dis. 2004;43(suppl 1):S1-S290.

Monitor response, manage side effectsMonitor response,

manage side effects



Introduce or increasediuretic or other agentIntroduce or increasediuretic or other agent

YesYes NoNo

Recommendations on Antihypertensive Recommendations on Antihypertensive Agents in CKDAgents in CKD

– 50% to 75% of patients with CKD have HTN50% to 75% of patients with CKD have HTN– HTN is a risk factor for development and HTN is a risk factor for development and

progression of kidney disease and development progression of kidney disease and development and worsening of CVD in CKDand worsening of CVD in CKD

– Antihypertensive therapy can slow progression of Antihypertensive therapy can slow progression of kidney disease and reduce risk of CVD in CKDkidney disease and reduce risk of CVD in CKD

– Antihypertensive agents can slow progression of Antihypertensive agents can slow progression of kidney disease, even in patients who are not kidney disease, even in patients who are not hypertensivehypertensive

Recommendations on Antihypertensive Recommendations on Antihypertensive Agents in CKD (cont’d)Agents in CKD (cont’d)

• Blood pressure goal of <130/80 mm Hg is Blood pressure goal of <130/80 mm Hg is appropriate for all types of CKDappropriate for all types of CKD– Patients with CKD are in the “highest-risk” Patients with CKD are in the “highest-risk”

group for CVDgroup for CVD– For most patients with CKD, 2 or more For most patients with CKD, 2 or more

antihypertensive agents will be necessary to antihypertensive agents will be necessary to achieve the blood pressure goalachieve the blood pressure goal

– Achievement of the target SBP of <130 mm Hg Achievement of the target SBP of <130 mm Hg is usually associated with reduction in DBP to is usually associated with reduction in DBP to <80 mm Hg<80 mm Hg

National Kidney Foundation. Am J Kidney Dis. 2004;43(suppl 1):S1-S290.

ACUTE CORONARY ACUTE CORONARY SYNDROMESSYNDROMES

• Renal dysfunction as the most significant prognostic factor for long-term mortality

• Comorbidities, in particular DM and HF• Therapeutic nihilism (underutilization of

proven therapies such as beta blockers, thrombolysis or primary angioplasty )

• Toxicity of therapies.• Biological and pathophysiological factors

in renal dysfunction

DIAGNOSIS OF ACUTE DIAGNOSIS OF ACUTE CORONARY SYNDROMES CORONARY SYNDROMES

• Patients with CKD presenting to the hospital with chest discomfort represent a high-risk group

• 40 % cardiac event rate at 30 days. • Higher silent ischemia rates .• Troponin I is the preferred biomarker.• Skeletal myopathy of CKD can elevate

creatine kinase, myoglobin, and some troponin T assays


• Excess thrombin generation and decreased platelet aggregation

• Increased rates of coronary thrombosis and increased bleeding


• LPL function ; HDL, TG, LDL• Elevations in homocysteine • Enhancing oxidation of LDL-C• progression of atherosclerotic lesions • High rate of plaque rupture &CVD events.• Imbalance between ET and NO, may

worsen HTN and may augment intravascular wall stress that could further contribute to CVD events.

TREATMENT OF ACUTE TREATMENT OF ACUTE MYOCARDIAL INFARCTION MYOCARDIAL INFARCTION

• Good benefit to risk ratio for ASA, beta blockers, ACEI, ARB, aldosterone receptor antagonists, and statins.

• dose adjustment for LMWH, bivalirudin, GP IIb/IIIa antagonists

CKDCKD and HFHF

• Pressure overload (related to HTN)

• Volume overload

• Cardiomyopathy

RENAL AND CARDIOVASCULAR INTERACTION

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