2. Introduction
Kidneys receive 20% to 25% of the cardiac output
Kidney has a central role in electrolyte balance, protein
production and catabolism, and blood pressure regulation
Communication between the heart and the kidneys
Sympathetic nervous system
Renin-angiotensin-aldosterone system
Antidiuretic hormone
Endothelin
Natriuretic peptides
Obesity contributes to type 2 diabetes mellitus and
hypertension predispose CKD and CVD
5. With age the eGFR declines from approximately 130 to 60
ml/min/1.73 m2
Variety of pathobiologic processes appear to begin when the
eGFR drops below 60 ml/min/1.73 m2
Critical cut point for CI-AKI, restenosis after PCI, recurrent
acute MI, diastolic or systolic heart failure, arrhythmias, and
cardiovascular death
Serum creatinine is a crude indicator of renal function and
often underestimates renal dysfunction in women and elderly
eGFR or CrCl calculated by MDRD equation and Cockcroft-Gault
equation provide superior assessment of renal function
6. Cystatin C also reflects renal filtration function
Independent of weight and height, muscle mass, age,
or sex
Less variable than serum creatinine
Microalbuminuria at any level of egfr indicates CKD
Random urine albumin-to-creatinine ratio (ACR) of 30 to 300
mg/g
Microalbuminuria independently predicts CVD for those with
and without diabetes
7. Implications of Anemia Due to CKD
Anemia due to CKD is present in 20% of patients with
stable coronary disease and 30% to 60% of patients with
heart failure
Relative deficiency of erythropoietin-alpha
Normal plasma EPO levels range between 10 and 30 IU/ ml
During anemic periods levels may be elevated up to 100
IU/ml
Increased circulating levels of hepcidin, an inhibitor of the
ferroportin receptor, impair iron absorption and utilization
Studies of heart failure found anemia to predict mortality
independently
8. Treatment of anemia with exogenous EPO or darbepoetin alfa
increasing the Hb level from below 10 g/dL to 12 g/dL can improve
left ventricular remodeling, EF, and functional classification and raise
levels of peak oxygen consumption with exercise testing
EPO can cause three problems:
(1) Increased platelet activity, thrombin generation, and resultant
increased risk of thrombosis
(2) Elevated endothelin and asymmetric dimethylarginine which
theoretically reduces nitric oxide availability, and results in
hypertension
(3) Worsened measures of oxidative stress
Treatment with ESPs may actually worsen CVD outcomes in CKD
ESPs should be reserved for the treatment of severe anemia in CKD
with the goal of improving symptoms and avoiding transfusion
9. CONTRAST-INDUCED ACUTE KIDNEY
INJURY
Iodinated CI-AKI defined by the Acute Kidney Injury Network
criteria of a 0.3mg/dL or greater rise in serum creatinine from
baseline within 48 hours of intravascular administration
Occurs in approximately 13% in nondiabetics and 20% of
diabetics undergoing PCI
CI-AKI leading to dialysis is rare (0.5% to 2.0%)
Severe CI-AKI is associated with catastrophic outcomes
including a 36% in-hospital mortality rate and a 2-year survival
rate of only 19%
Transient rises in serum creatinine
Longer length of hospital stay, MI, stroke, heart failure, and
rehospitalization
10. Pathophysiology of CI-AKI
(1) Direct toxicity of iodinated contrast material to nephrons,
(2) Microshowers of atheroemboli to the kidneys (consequent to
catheter and wire exchanges above the renal arteries)
(3) Contrast material and atheroemboli induced intrarenal
vasoconstriction of the vasa recta
Direct toxicity to nephrons with iodinated contrast media appears to
be related to the ionicity and osmolality of the contrast media
1% of high-risk cases acute cholesterol embolism syndrome
acute renal failure
mesenteric ischemia,
decreased microcirculation to the extremities
embolic stroke
11.
12. Prevention of Contrast-Induced
Acute Kidney Injury
Patients with baseline eGFR < 60 mL/min/1.73 m2, in particular, those
with CKD and diabetes mellitus, should receive preventive measures for
CI-AKI
Other risk factors
Hemodynamic instability, use of intra-aortic balloon counterpulsation,
heart failure, older age, and anemia
CI-AKI 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
13.
14. Hydration with intravenous normal saline or isotonic sodium
bicarbonate is reasonable, starting 3 to 12 hours before the procedure
at 1 to 2 ml/kg/hr
Patients at risk and able to tolerate the fluid load should receive at
least 300 to 500 ml of intravenous hydration fluid before contrast
Right-heart catheterization may aid in patients with heart failure
Postprocedure hydration target is a urine output of 150 ml/hr
Urinary excretion rates of more than 150 ml/hr should have
intravenous replacement of extra losses
Normal saline or sodium bicarbonate at 150 ml/hr for at least 6 hours
after the procedure
15. RCT of iodinated contrast agents have demonstrated the lowest rates of CI-
AKI with nonionic, iso-osmolar iodixanol
Relative risk of CI-AKI occurring for iodixanol was 0.46 (P = 0.004), compared
with LOCM
16. Contrast volume should be minimized in any setting, and there is
disagreement about a “safe” contrast limit
Maximum target volumes of contrast medium should be less than 30
mL for a diagnostic and less than 100 mL for an interventional
procedure
In staged procedures, more than 10 days should elapse between the
first and second contrast exposures if CI-AKI has occurred with the
first procedure
17. (1) Loop diuretics or mannitol can worsen CI-AKI if volume
replacement is inadequate for the diuresis that follows
(2) Low-dose or “renal dose” dopamine or fenoldopam does not
provide protection, given the counterbalancing forces of intrarenal
vasodilation through the dopamine-1 receptor and the
vasoconstricting forces of the dopamine-2, alpha, and beta receptors
(3) Renal toxic agents including NSAID, aminoglycosides, and
cyclosporine should not be administered in the periprocedural period
N-acetylcysteine 1200 mg by mouth twice daily the day before and
after the procedure showed no differences in the rates of CI-AKI,
ESRD, or other outcomes
18.
19.
20. CARDIAC SURGERY–ASSOCIATED ACUTE
KIDNEY INJURY
AKI occurs in approximately 15% of patents after forms of cardiac
surgery with or without use of cardiopulmonary bypass
Many factors including endogenous/exogenous toxins, metabolic
factors, ischemia and reperfusion, neurohormonal activation,
inflammation, and oxidative stress contribute to renal tubular injury
In children undergoing cardiac surgery, urine neutrophil gelatinase
associated lipocalin is markedly elevated in those who will go on to
develop AKI
Other novel cardiac markers
Urine kidney injury molecule 1, L-type fatty acid binding protein,
alpha-glutathione S-transferase (alpha- GST), pi-GST, and other
proteins that indicate renal tubular cell cycle arrest and apoptosis
22. ACCELERATION OF VASCULAR
CALCIFICATION
At eGFR below 60 mL/min/1.73 m2, the filtration and elimination of
phosphorus fall and 1,25D3 production decreases relative hypocalcemia
Thus subtle degrees of hyperphosphatemia and hypocalcemia increase release
of PTH causing liberation of calcium and phosphorus from bone
The bone in turn produces greater amounts of FGF-23 which directs the
kidneys to increase the clearance of phosphorus
This abnormal bone and mineral metabolism markedly increase absolute
values and rates of accumulation of arterial calcium
No strategies that manipulate calcium-phosphorus balance or treat secondary
hyperparathyroidism significantly influence the progression of coronary
calcification or decrease cardiovascular events in patients with ESRD
23. RENAL DISEASE AND HYPERTENSION
Sodium retention stimulates increases in systemic and renal arteriolar
pressure in an attempt to force greater degrees of filtration in the
glomerulus
Glomerular injury activates several pathways that can increase
systemic blood pressure
Combined CKD and CVD is strict blood pressure control with a target
of less than 130/80 mm Hg
Sodium restriction, weight reduction of 15% to a target BMI <25 kg/
m2, and exercise for 60 minutes/day most days of the week
RAAS inhibitors often in combined action with a thiazide type diuretic
24. Dihydropyridine calcium channel blocker monotherapy should be avoided
because of relative afferent arteriolar dilation increased intraglomerular
pressure and worsen glomerular injury.
Combinations of multiple RAAS-blocking drugs— ACEi, ARB, direct renin
inhibitor—have not shown superiority to single agents in this class and cause
more complications
Percutaneous renal artery denervation is undergoing evaluation
25. DIAGNOSIS OF ACS IN PATIENTS WITH
CKD
Patients with CKD have higher rates of silent ischemia, risk of serious
arrhythmias, heart failure, and other cardiac complications
In stable outpatients with CKD, 38% and 68% will have a high-
sensitivity cTnI and cardiac troponin T (cTnT) above the 99th
percentile of normal
Degree of elevation of cTn reflects left ventricular mass and the
severity of renal disease
cTnI serves best for diagnostic evaluation of patients with CKD or
ESRD experiencing acute chest discomfort, whereas chronic elevations
of cTnT are more common and more prognostic in stable patients
The skeletal myopathy of CKD can elevate creatine kinase, myoglobin,
and some older-generation cTnI/cTnT assays
26. Renal Dysfunction as a Prognostic Factor
in ACS
Patients with CKD represent 30.5% of STEMI cases and 42.9% of NSTEMI cases
and CKD is associated with higher rates of in-hospital mortality in a graded
fashion with worsened renal function
27. Reasons for Poor Outcomes after ACS in
Renal Dysfunction
(1) Excess comorbid conditions associated with CKD and ESRD, in particular,
diabetes mellitus and left ventricular dysfunction
(2) Therapeutic nihilism
(3) Toxicity of therapies
(4) Special biologic and pathophysiologic factors in renal dysfunction that
cause worsened outcomes
Defects in thrombosis attributable to uremia include excess thrombin
generation and decreased platelet aggregation
Increased rates of coronary thrombotic events and increased bleeding risks at
the same time
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38. Data support a favorable benefit-to-risk ratio for aspirin, beta-adrenergic
blocking agents (beta blockers), ACE inhibitors, ARBs, aldosterone receptor
antagonists, and statins
Therapies that require dose adjustment on the basis of CrCl include low-
molecular-weight heparins, bivalirudin and glycoprotein IIb/IIIa antagonists
SWEDEHEART study reported a benefit to revascularization in ACS in CKD
patient groups with eGFR of 15 mL/min/1.73 m2 or greater
39. CARDIORENAL SYNDROMES
Cardiorenal syndrome refers to disorders of the heart and
kidneys whereby acute or chronic dysfunction in one organ
may induce acute or chronic dysfunction in the other
Most common application of the designation cardiorenal
syndrome is in patients with heart failure
40.
41. CKD, and in particular ESRD, have three key mechanical contributors
to heart failure: pressure overload (related to hypertension), volume
overload, and cardiomyopathy
20% of patients approaching hemodialysis have pre-existing heart
failure
CKD influences the blood levels of B-type natriuretic peptide (BNP)
and NT-proBNP
eGFR is less than 60 mL/min/1.73 m2, higher cut points of 200
pg/mL and 1200 pg/mL should be used in the diagnosis of heart
failure
ADHF approximately 25% will develop a cardiorenal syndrome during
the hospitalization characterized by a rise in serum creatinine to 0.3
mg/dL or higher and a reduction in urine output
42.
43. Multiple studies have shown that the predictors of cardiorenal
syndrome (type 1) include baseline egfr, older age, female sex,
increased baseline blood pressure, higher initial natriuretic peptide
levels, and increased central venous pressure
Type 1 in patients with heart failure rarely occurs in the prehospital
phase
Loop diuretics, probably by further activating the RAAS and possibly
worsening intrarenal hemodynamics
Elevated serum creatinine is the most common reason for the use of
positive inotropes or inodilators in hospitalized patients with heart
failure
Hyponatremia and excess body water are ameliorated slightly with
oral tolvaptan or intravenous conivaptan; however, neither therapy
reduces rehospitalization or mortality
44. Cardiorenal rescue study in acute decompensated heart failure
(CARRESS-HF) in patients with persistent congestion and renal
dysfunction found no clinical benefits of ultrafiltration over diuretic
therapy
Retrospective analyses supports the use of an ACE inhibitor or ARB
(not the combination) in patients with ESRD with heart failure
Frequent outpatient monitoring and avoidance of overly aggressive
diuresis are advised.
Dialysis patients, despite having volume reduction with mechanical
fluid removal, should have medical therapy with ACE inhibitors or
ARBs, beta blockers, and additional agents for blood pressure control
45.
46. CKD AND VALVULAR HEART DISEASE
Aggravate mitral annular calcification and aortic valve sclerosis
80% of patients with ESRD have the murmur of aortic sclerosis
Bacterial endocarditis may develop in patients with ESRD who have
temporary dialysis access catheters
Staphylococcus, streptococcus, and enterococcus, in the mitral,
aortic, or tricuspid valves, carries a risk of cerebral embolism of 40%
and a mortality rate of 50% in ESRD
Valve replacement in ESRD for endocarditis carries a very high
mortality rate
Tissue or mechanical valve prostheses demonstrate similar survival
47. RENAL FUNCTION AND ARRHYTHMIAS
Uremia, hyperkalemia, acidosis, and disorders of calcium-phosphorus
balance all link to higher rates of atrial and ventricular arrhythmias
Concurrent LVH, left ventricular dilation, heart failure, and valvular
disease all contribute
Dose adjustment required for many antiarrhythmic medications
ESRD benefit from implantable cardioverter-defibrillators (ICDs)
implantation for secondary prevention
ESRD may cause elevated defibrillation thresholds and failure of ICDs
and lead to high rates of shock and antitachycardia pacing
48.
49.
50. CONSULTATIVE APPROACH TO SEVERE KIDNEY
DISEASE AND HEMODIALYSIS PATIENTS
Prevalence of angiographically significant CAD ranges from 25% in
young, nondiabetic hemodialysis patients up to 85% in older patients
with ESRD who have long-standing DM
Rate of cardiac death in dialysis patients younger than age 45 exceeds
by 100-fold that in the general population
Third of diabetic renal transplant candidates have one or more lesions
with greater than 75% stenosis
ESRD patients have substantially more numerous, proximal, and
severe coronary artery lesions, as well as more severe left ventricular
dysfunction
Hypertension affects 80% of patients with ESRD, and only 30% achieve
adequate control
51. Risk of coronary heart disease death by gradations of CKD
and diabetes; USRDS = US Renal Data Systems
52. Long-term cardiorenal protection involves two important concepts:
blood pressure control to a much lower target of a systolic blood
pressure less than 130 mm Hg
use of an agent that blocks the RAAS
ACE inhibitors/ARBs can reduce LVH and possibly improve survival
Beta blockers can serve as both antihypertensive and anti-ischemic
agents
Improve LVEF and reduce rates of hospitalization, sudden death,
and all-cause mortality
Achieve these goals without inducing hypotension during dialysis
sessions
Hypotension during dialysis can worsen clinical and subclinical
ischemia recognized as chest discomfort, shortness of breath, ST-
segment depression on electrocardiography, and elevations of cTn
on blood testing
53. LDL cholesterol reduction, in most cases with a statin and ezetimibe,
in patients with ESRD is supported by a 17% reduction in major
atherosclerotic events
In DM blood glucose control to a target glycohemoglobin below 7
mg/dl
Smoking cessation as another basic reduction manoeuvre
Chronic administration of antiplatelet agents (aspirin and clopidogrel)
as well as warfarin has been associated with increased risk of death in
ESRD
Preventive use should be undertaken with caution
Stable symptomatic CAD COURAGE trial suggested PCI had no
benefit over optimal medical therapy
No similar trial data are available for patients with ESRD
54. In multivessel disease, multiple studies have shown that outcomes
after CABG are superior to those achieved with PCI with DES
Dialysis dependent patients undergoing CABG
4.4-fold increased risk of in-hospital death
3.1 times greater risk of mediastinitis
2.6-fold increased risk of stroke
Aggressive approach with medical management for CAD is warranted,
even in the case of subclinical CAD
A low threshold for diagnostic testing is appropriate in patients with
ESRD
55. EVALUATION AND MANAGEMENT
OF THE RENAL TRANSPLANT RECIPIENT
Cardiovascular screening is recommended in high-risk CKD patients
before renal transplantation
DM
Men >45 years ; Women >55 years
Previous H/o IHD
An abnormal ECG
Left ventricular dysfunction
Smoker
Duration of dialysis more than 2 years
Modality exercise versus pharmacologic stress and
echocardiographic versus nuclear scintigraphic imaging must be
individualized