Risk Factors for Acute Kidney Injury in Congenital Heart Defects Ronald G. Grifka, MD Chief,...

Risk Factors for Acute Kidney Injury in Congenital Heart

Defects

Ronald G. Grifka, MDChief, Cardiology Division Helen DeVos Children’s HospitalProfessor of Pediatrics MSU College of Human Medicine


DefectsThe Elephant…


Defects

• Hypertension• FeNa• GFR Calculations• Lupus

What I Will Not Discuss


Defects

• Normal cardiac index = 3.5 L/min/m2

• Cardiac index = cardiac output/BSA

• For a newborn: 3.2 kg, 0.22 m2

• Cardiac output = 770 ml/min• If HR = 140/min• Each heart beat = 5.5 ml

• RBF = 20% of the CO- RBF = 1.1 ml/heart beat

Cardiac Hemodynamics


Defects

• Low cardiac output state: CI = 2.0 L/min/m2

• For a newborn: 3.2 kg, 0.22 m2

• Cardiac output = 440 ml/min• If HR = 170/min• Each heart beat = 2.6 ml

• RBF = 20% of the CO• RBF = 0.52 ml/heart beat

Cardiac Hemodynamics


Defects

• Acute vs. Chronic• New post-op, Myocarditis vs. Dilated CM, DMD, old post-op

• Right ventricle vs. Left ventricle• TOF, Pulm HTN vs. Anomalous left cor art from PA, DCM

• High output vs. Low output• Anemia, Hyperthyroid vs. DCM, Myocarditis

• Congenital vs. Acquired• Mitochondrial disorder, DMD vs. Kawasaki disease, Myocarditis

Types of Heart Failure


Defects

• Left to right shunts• VSD, PDA, AV Canal, ASD

• Right to left shunts• TOF, Pulmonary atresia

• Transposition physiology• Obstructive / Regurgitant defects

• AS, PS, CoA, “HLHS”, MS, MR, AI

• Cardiomyopathy• Dilated, Hypertrophic, Restrictive

5 Physiologies of Congenital Heart Defects


Defects

• VSD, AV Canal, PDA, ASD, Ao-PA Window, Truncus arteriosus, Single V without PS

• Results in pulmonary overcirculation• *RARELY causes heart failure (”CHF”), renal

failure• Tx: Diuretics, ACE inhibitor, ± digoxin• *Neonates - Truncus Arteriosus, Premie (PDA)

- Intestinal steal NEC, Renal failure

Physiology #1 Left to Right Shunt


Defects

• Tetralogy of Fallot, Pulmonary atresia, Single ventricle with PS

• Does not cause pulmonary overcirculation!• Does not cause heart failure (”CHF”)• Does cause: Cyanosis, Polycythemia, Bleeding • Partial exchange transfusion if Hct > 62-65%

Physiology #2 Right to Left Shunt


Defects

• Blue blood to the body, red blood to the lungs• Not compatible with life as we know it!

• Profoundly cyanotic, hypoxic, acidotic, hypotensive• Can cause multi-system organ damage if not

treated immediately• Immediate treatment:

• PDA (PGE1 infusion)• ASD (Balloon atrial septostomy)

Physiology #3 Transposition Physiology


Defects

• Aortic stenosis/regurge, Pulmonary stenosis, Coarctation of the aorta, “HLHS”, Mitral stenosis or regurge

• CAN cause heart failure!• CAN cause inadequate perfusion to:

• Coronaries (infarction)• Intestines (NEC)• Kidneys (ARF)

Physiology #4 Obstructive/Regurgitant Defects


Defects

• Dilated, Hypertrophic, Restrictive• CAN cause heart failure!

• LHF: Inadequate organ perfusion, Pulm edema, SOB, Activity• RHF: 1° or 2°, Hepato-splenomegally, systemic edema

• DCM: Diuresis, ACE inhibitor, Inotrope, ± Anti-arrhythmic• HCM: NO: diuresis or inotrope (unless end stage)

YES: beta blocker, ± Anti-arrhythmic, AICD

• End stage Tx: LVAD (DCM), Heart transplant

Physiology #5 Cardiomyopathy


Defects

• Acute insult

• Chronic insult

• An acute insult to a chronic condition

Cardiac Related Renal Injury


Defects

• Myocarditis• Acute bacterial endocarditis• CHD with acute decompensation (URI)

• Aortic stenosis, CoA, DCM

• Catheterization / IV Contrast• Open heart surgery / CPB• Heart transplant

• Rejection, meds, infection

• Trauma (hemorrhage, etc)

Cardiac Related Renal Injury - Acute Insult


Defects

• (Systemic) Ventricular failure• CHD, DCM natural history• Post-op failure• Myocarditis• Transplant: Coronary vasculopathy,

rejection, meds, infection

• Cyanosis• Repetitive embolic events

• Arrhythmia, thrombotic substrate

Cardiac Related Renal Injury - Chronic Insult


Defects

• Nephrotoxic antibiotics• Furosemide, mannitol Diuresis, but IVF not replaced• Epi, Norepi, high dose Dopamine Renal vasoconstriction• Anesthetic agents Hypotension• Low cardiac output, low blood pressure• Sepsis• Pre-existing renal disease (cyanosis, Hct, low cardiac output)

• Cardiopulmonary bypass

Peri-Operative Renal Insults


Defects

• Allows surgery in a bloodless field• Arrests the heart, decreases MVO2• Perfuses other organs during surgery• Can adjust the blood flow, add medications

Cardiopulmonary Bypass - Positives


Defects


Defects

• Fragments RBC’s• Activates platelets• Alters clotting factors• Liberates vasoactive compounds• Hypothermic insult (18-25° C)• Metabolic acidosis• Perfuses organs during surgery with

NON-PULSATILE flow• P/O transfusions

Cardiopulmonary Bypass – Negatives


Defects

• Phenoxybenzamine pre-op• Increase renal blood flow

• Dopamine, fenoldapam, neseritide

• Intra-op, Post-op diuretics• ± IVF replacement: colloid vs. crystalloid

• Increase BP• But pressors SVR, HR , ? CO

• Peritoneal dialysis

Peri-Operative Treatment

BeBenephnephititTMTM Infusion System Infusion System(FlowMedica, Inc., Fremont, CA)(FlowMedica, Inc., Fremont, CA)

FDA (510K) Cleared January 2004FDA (510K) Cleared January 2004

Intrarenal infusionIntrarenal infusion

-Dopamine, Fenoldopam-Dopamine, Fenoldopam

-Nesiritide (BNP)-Nesiritide (BNP)


Defects

• Enlargement of the glomerular capillary tuft• Mesangial hypercellularity• Accumulation of eosinophilic material• Capillary basement membrane thickening• IgM deposits in the mesangium• Fibrin in the glomerular capillary walls• Clinically – GN: hematuria, proteinuria, HTN

Cyanotic Heart Disease


Defects

• Kidneys normal to slightly enlarged• Glomerular immune complex deposition

- C3, IgG. Occasionally IgM, IgA

• Treat SBE, renal function improves• Advanced SBE disease

• Microabcesses• Embolization, infarction

• May not recover renal function

Infective Endocarditis


Defects

• Well described entity in adults• Adults have more pre-existing renal disease, HTN• Rare in children following cardiac cath

• New contrast much safer• IVF from anesthesiologist and catheter flushes• Contrast given over several hour cath procedure

- Up to 12 ml/kg over 7 hr procedure• Much IV fluids, foley

Contrast Induced Nephropathy

The Evolution of Contrast MediaThe Evolution of Contrast Media

R

R

RRR

R

CH3CONH

RRR

II

II

IIII

IIII

II

RR

II

R COO–Na+/Meg+

I

R

COO–Na+/Meg+

I

Ionic monomerDiatrizoateIothalamate

Nonionic monomerIopamidol

IohexolIoversol

Ionic dimerIoxaglate

Nonionic dimerIodixanol(Iotrolan)

ExamplesMolecular Structure Era

1950s

1980s

1980s

1990s

Comment

High Osmolality, 5 – 8 blood

Low Osmolality,2 – 3 blood,

improved hydrophilicity

Low Osmolality,~2 blood

Iso-osmolalityOsmolality = blood

Osmolalities of Contrast MediaOsmolalities of Contrast Media

Iodixanol is a nonionic dimer, formulated with balanced levels of Ca2+ and Na+, that is isosmolar with plasma at all iodine

concentrations

0

500

1000

1500

2000

2500Blo

odIo

dixa

nol

Ioxa

glat

eIo

mep

rol

Iove

rsol

Iopr

omid

eIo

pam

idol

Iope

ntol

Iohe

xol

Iobi

trid

olDia

triz

oate

Osm

ola

lity

(m

Osm

/kg

H

2O)

+

*

* 320 mg I/mL† 350 mg I/mL‡ 370 mg I/mL

* *†† † †

‡ ‡

‡

Contrast enters renal vasculatureEndothelium-independent transient vasodilation (minutes)

Reduced nephron mass vulnerable to injuryAssociated factors: diabetes, poor renal perfusion, others

Sustained intrarenal vasoconstriction (hours)

Ischemic injury and death

Acute Kidney Injury

Prostaglandindysregulation

Decreased Nitric Oxide Synthesis/Release

Prolonged contrast transit time in kidneysIncreased contrast exposure to renal tubular cells

Contrast direct cellular injury and death

Medullary hypoxia

Catalytic iron-driven oxidative Stress, inflammation, other organ injury processes

Adenosine release from macula densa

(tubulo-glomerular feedback)

Endothelinrelease

McCullough PA, JACC 2008

73 y/o with multiple myeloma, Cr 2.3 mg/dl, CrCl=23 ml/min, Cr rise 0.3 mg/dl

Nephrol Dial Transplant (2004) 19: 1654–1655

One-Year Kaplan-Meier Survival Curves Stratified by CrCl Levels after Primary Angioplasty in CADILLAC

Time (days)

Su

rviv

al (%

)

CrCl >60CrCl >60CrCl 50-60CrCl 50-60

CrCl 40-50CrCl 40-50CrCl 30-40CrCl 30-40

CrCl 20-30CrCl 20-30

CrCl <20CrCl <20

PP<.0001 (all groups)<.0001 (all groups)40

50

60

70

80

90

100

0 50 100 150 200 250 300 350 400 450 500

Sadeghi HM et al. Circulation. 2003;108:2769–2775.

*Plans should be made in case AKI occurs and dialysis is required

† Potentially beneficial agents:

N-Acetylcysteine

Ascorbic acid

Aminophylline

Prostaglandin E1

None approved for this indication

AKI=acute kidney injuryCr = creatinineCrCl=creatinine clearance; eGFR=estimated glomerular filtration rate NSAIDs= nonsteroidal anti-inflammatory drug

Calculate eGFR or CrClCalculate eGFR or CrClAssess contrast-induced AKI riskAssess contrast-induced AKI risk

eGFR <30 ml/mineGFR <30 ml/minStart/continue statinStart/continue statin

Discontinue NSAIDs, Discontinue NSAIDs, other nephrotoxic drugs, metforminother nephrotoxic drugs, metformin

eGFR 30-59 mL/mineGFR 30-59 mL/minStart/continue statinStart/continue statin

Discontinue NSAIDs, other nephrotoxic Discontinue NSAIDs, other nephrotoxic drugs, metformindrugs, metformin

eGFR eGFR ≥≥60 ml/min60 ml/minDiscontinue metforminDiscontinue metformin

• Hospital admissionHospital admission

• Other strategies as for Other strategies as for eGFR 30-59 mleGFR 30-59 ml

• Nephrology Nephrology consultation*consultation*

• Consider hemofiltration Consider hemofiltration pre- and post-procedurepre- and post-procedure

• IV isotonic (NaCl/NaHCOIV isotonic (NaCl/NaHCO33))•1.0-1.5 ml/kg/min 3-12 hrs pre and 6-24 post1.0-1.5 ml/kg/min 3-12 hrs pre and 6-24 post

•Ensure urine flow rate > 150 ml/hrEnsure urine flow rate > 150 ml/hr

• Iso-osmolar contrastIso-osmolar contrast•DM, ACS, other added risksDM, ACS, other added risks

• Low osmolar contrastLow osmolar contrast•No other added risksNo other added risks

• Limit contrast volumeLimit contrast volume•< 30 cc diagnostic< 30 cc diagnostic

•<100 cc diagnostic+intervention<100 cc diagnostic+intervention

• Consider adjunctive medicationsConsider adjunctive medications††

•AntioxidantsAntioxidants

•N-acetylcycteine 1200 mg po bid pre- N-acetylcycteine 1200 mg po bid pre- and post-procedureand post-procedure

oror

•Ascorbic acid 3 g po pre- Ascorbic acid 3 g po pre-

2 g po bid post-procedure2 g po bid post-procedure

Good clinical Good clinical practicepractice

Serum Cr before Serum Cr before discharge or 24–72 hrdischarge or 24–72 hr

Expectant CareExpectant Care

IV Hydration and Urine OutputIV Hydration and Urine Output

Stevens MA et al. J Am Coll Cardiol. 1999.

4.5

3.5

2.5

1.5

0.5

-0.5

-1.5

Ch

an

ge in

Cr

from

Baselin

e

(mg

/dL)

0 60 120 180 240 300

Urine Flow Rate (mL/h)

r = -0.36, F = 5.73, r = -0.36, F = 5.73, PP = 0.005 = 0.005Urine Flow Rate (mL/hr), beta = -0.36, t = -3.33, Urine Flow Rate (mL/hr), beta = -0.36, t = -3.33, PP = 0.001 = 0.001

Baseline CrCI (mL/min), beta = 0.10, t = 0.93, Baseline CrCI (mL/min), beta = 0.10, t = 0.93, PP = 0.36 = 0.36

Regression 95% CI

Treitl M, et al, Nephrol Dial Transplant (2008)Treitl M, et al, Nephrol Dial Transplant (2008)

Hemofiltration Hemofiltration works to ensure

– Adequate intravascular volume– Reduce uremic toxins which may worsen AKI– Provides stability to the high risk patient after the procedure reducing the

risks of oliguria, volume overload, and electrolyte imbalance that are associated with short-term mortality.

Double lumen catheter is placed in a jugular or femoral vein for blood withdrawal and reinfusion and connected to an extracorporeal circuit.

6 hours before contrast: Peristaltic pump (e.g. Prisma hemofiltration pump) at 100 mL/min. Isotonic replacement fluid (post-dilution hemofiltration) 1000 mL/h, matched with the rate of ultrafiltrate production so no net fluid loss occurs.

5000 IU heparin bolus before initiation followed by a continuous heparin infusion of 500 to 1000 IU/h through the inflow side of the catheter.

At the time of the cardiac procedure, the hemofiltration treatment should be stopped, the circuit temporarily filled with a saline solution and short-circuited to exclude the patient without interruption of the flow.

Immediately after the cath, hemofiltration should be restarted for 12-18 hours.

AKI (Cr >0.5 mg/dL [> 44.2µmol/L])

Marenzi G et al. Am J Med. 2006 Feb;119(2):155-62.

47

42

3

0

10

20

30

40

50

Control Post-hemofiltration

group

Pre/post-hemofiltration

group

%

P<0.001

NS

Dialysis

9 (30%) 3 (10%) 0 (0%) P=0.002

Death

6 (20%) 3 (10%) 0 (0%) P=0.03

Anatomical Basis: The Coronary SinusAnatomical Basis: The Coronary Sinus

69 y.o. with CRI, SCr. 2.9, CTO, 240cc dye69 y.o. with CRI, SCr. 2.9, CTO, 240cc dye

AIVAIV

CSCS

AIV

AIV

MC

VM

CV

Sensor (Optical Reflectance)

• Delivery fiber shines monochromatic, visible light into blood

• Interactions between light and blood cells results into back-scattering of photons, which are captured by detection fiber

• Amount of scattered light is proportional to optical density of blood (i.e. number of blood cells per volume).

• Signal drop registered when contrast bolus passes by tip of sensor system

DeliveryDelivery

DetectionDetection

[1] Signal represents contrast presence in coronary sinus[1] Signal represents contrast presence in coronary sinus

Contrast Detection Signal Contrast Detection Signal [1][1]

•Successful device deployment in CS

•Arterial injection of contrast

•Appropriate size & seal at CS level

•Contrast recovery: 70%*

Source: CAN-12 CD1_IMG008Source: CAN-12 CD1_IMG008 * Contrast recovery established by UV Spectrometry* Contrast recovery established by UV Spectrometry

In-Vivo Contrast RemovalIn-Vivo Contrast Removal


Defects

This is not the end.Nor is it the beginning of the end.But perhaps, this is the end of the beginning.


DefectsThank you, and looking toward the future in Grand Rapids….


Defects


Defects

Ronald G. Grifka, MDChief, Cardiology Division Helen DeVos Children’s HospitalProfessor of Pediatrics MSU College of Human Medicine

Risk Factors for Acute Kidney Injury in Congenital Heart Defects Ronald G. Grifka, MD Chief,...

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