Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Ronald G. Grifka, MD
Chief, Cardiology Division
Helen DeVos Children’s Hospital
Professor of Pediatrics
MSU College of Human Medicine
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
The Elephant…
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
The Elephant…
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
What I Will Not Discuss
• Hypertension
• FeNa
• GFR Calculations
• Lupus
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Hemodynamics
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Hemodynamics
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Types of Heart Failure
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
5 Physiologies of Congenital Heart 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #1 Left to Right Shunt
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #2 Right to Left Shunt
• 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%
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #3 Transposition Physiology
• 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)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #4 Obstructive/Regurgitant 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)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Physiology #5 Cardiomyopathy
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury
• Acute insult
• Chronic insult
• An acute insult to a
chronic condition
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury - Acute Insult
• 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)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiac Related Renal Injury - Chronic Insult
• (Systemic) Ventricular failure
• CHD, DCM natural history
• Post-op failure
• Myocarditis
• Transplant: Coronary vasculopathy,
rejection, meds, infection
• Cyanosis
• Repetitive embolic events
• Arrhythmia, thrombotic substrate
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Peri-Operative Renal Insults
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiopulmonary Bypass - Positives
• Allows surgery in a bloodless field
• Arrests the heart, decreases MVO2
• Perfuses other organs during surgery
• Can adjust the blood flow, add medications
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cardiopulmonary Bypass – Negatives
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Peri-Operative Treatment
• 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
BenephitTM Infusion System
(FlowMedica, Inc., Fremont, CA)
FDA (510K) Cleared January 2004
Intrarenal infusion
-Dopamine, Fenoldopam
-Nesiritide (BNP)
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Cyanotic Heart Disease
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Infective Endocarditis
• 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
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Contrast Induced Nephropathy
• 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
The Evolution of Contrast Media
Molecular Structure Era Examples Comment
COO–Na+/Meg+ Ionic monomer High Osmolality,
I I 1950s
Diatrizoate 5 – 8 blood
Iothalamate
CH3CONH R
I
R Nonionic monomer Low Osmolality,
I I 1980s Iopamidol 2 – 3 blood,
Iohexol improved
R R Ioversol hydrophilicity
I
R COO–Na+/Meg+
Ionic dimer Low Osmolality,
I II I 1980s Ioxaglate ~2 blood
R R R
I I
R R Nonionic dimer
1990s Iso-osmolality
I II I Iodixanol Osmolality = blood
(Iotrolan)
R R R
I I
Osmolalities of Contrast Media
* 320 mg I/mL
† 350 mg I/mL
(mOsm/kg H2O)
2500 ‡ 370 mg I/mL ‡
Osmolality
+
2000
1500
† † †
1000 ‡ ‡
† *
*
500 *
0
Iodixanol is a nonionic dimer, formulated with balanced levels of
Ca2+ and Na+, that is isosmolar with plasma at all iodine concentrations
Reduced nephron mass vulnerable to injury
Associated factors: diabetes, poor renal perfusion, others
Contrast enters renal vasculature
Endothelium-independent transient vasodilation (minutes)
Adenosine release from Endothelin Prostaglandin
macula densa release dysregulation
(tubulo-glomerular feedback)
Decreased Nitric Oxide Synthesis/Release
Sustained intrarenal vasoconstriction (hours)
Prolonged contrast transit time in kidneys Medullary hypoxia
Increased contrast exposure to renal tubular cells
Contrast direct cellular injury and death Ischemic injury and death
Catalytic iron-driven oxidative Stress, inflammation, other organ injury processes
McCullough PA, JACC 2008
Acute Kidney Injury
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
100
CrCl >60
CrCl 50-60
90
CrCl 40-50
Survival (%)
CrCl 30-40
80
70
CrCl 20-30
60
CrCl 150 ml/hr
• Nephrology • Iso-osmolar contrast
consultation* •DM, ACS, other added risks *Plans should be made in case AKI
occurs and dialysis is required
• Consider hemofiltration • Low osmolar contrast
pre- and post-procedure •No other added risks † Potentially beneficial agents:
• Limit contrast volume N-Acetylcysteine
•0.5 mg/dL [> 44.2µmol/L])
Dialysis
9 (30%) 3 (10%) 0 (0%) P=0.002
Death
6 (20%) 3 (10%) 0 (0%) P=0.03
NS
50 47
42
P<0.001
40
30
%
20
10
3
0
Control Post- Pre/post- Marenzi G et al. Am J Med.
hemofiltration hemofiltration 2006 Feb;119(2):155-62.
group group
Anatomical Basis: The Coronary Sinus
69 y.o. with CRI, SCr. 2.9, CTO, 240cc dye
MCV
Sensor (Optical Reflectance)
• Delivery fiber shines monochromatic,
visible light into blood
Delivery
• Interactions between light and blood cells
Detection
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). Contrast Detection Signal [1]
• Signal drop registered when contrast
bolus passes by tip of sensor system
[1] Signal represents contrast presence in coronary sinus
In-Vivo Contrast Removal
• Successful device
deployment in CS
• Arterial injection of contrast
• Appropriate size & seal at
CS level
• Contrast recovery: 70%*
Source: CAN-12 CD1_IMG008 * Contrast recovery established by UV Spectrometry
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
This is not the end.
Nor is it the beginning of the end.
But perhaps, this is the end of the beginning.
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Thank you, and looking toward the future in Grand Rapids….
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Risk Factors for Acute Kidney
Injury in Congenital Heart Defects
Ronald G. Grifka, MD
Chief, Cardiology Division
Helen DeVos Children’s Hospital
Professor of Pediatrics
MSU College of Human Medicine