The Kidney and the Heart-too dry or too wet?
Disclosure information Alan Maisel MD Research support: Alere,Abbott,BrahmsThermoFisher,Nanosphere Consultant: Alere
Mr. Smith. • Patient seen in ED with acute shortness of breath and a headache. • He has long- standing NYHA II HF, secondary to hypertension and diabetes with an EF of 33%. • During his last outpatient visit one month ago, his “dry bnp” was 340 pg/ml and his creatinine was 1.6 mg/dl • He has been maintained on Lisinopril 10 mg, Carvedilol 25 mg bid, Spironolactone 25 mg, and furosemide 40 mg bid.
Exam • • • • •
Bp 110/70- mmHg HR 98 bpm- resp rate 24 Rales at bases JVP 16 cm + S3 peripheral edema
LABS • • • • • • •
Sodium 138 mmol/l Potassium 4.7 mmol/l BUN 26 Creatinine 1.9 mg/dl egfr- 45 BNP 1140 pg/ml troponin 0.06 ng/ml ( 99% 0.04) ecg sinus tachycardia
What is the likelihood he has or will develop worsening renal function during hospitalization?
A. 10% B. 30% C. 50% D. 80%
“Type 1 CardioRenal Syndrome ” Also know as: Worsening Renal Function (WRF) or Acute Kidney Injury (AKI)
100 80
% Cr
≥0.1
60
≥0.2
40
≥0.3 ≥0.4
20 0
X 1
X X X X X X X X X X X X ≥0.5 X X 3
5
7
9
11
Days Cr, serum creatinine. Gottlieb SS et al. J Card Fail. 2002;8:136. Smith G, J Card Fail. 2003 Feb;9(1):13-25
13
15
ADQI VII: The Cardio-Renal Syndrome
THE CARDIO-RENAL SYNDROME General Definition: We defined the broad term “Cardio-Renal Syndromes” as “disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”.
The Cardio-Renal Syndrome
Treatment of the Cardiorenal Syndrome 5 important questions…
• • • • •
What is the fluid status? Is the blood pressure adequate for renal perfusion? What is the cardiac output? Is there evidence of high central venous pressure? Is there intrinsic renal disease?
Profiles of the Cardiorenal Syndrome CRS due to:
Fluid Status
CO CI
SVR
Proteinuria
Treatment
Hypovolemia
dry
low
Nml or high
none
Fluids, stop diuretics
Excess Vasoconstriction
Wet or nml
low
High
none
ACEI, nesiritide
Cardiogenic Shock/Low Output
Wet or Nml
Low
Normal
none
Inotropes, pressors, balloon pump, LVAD, Tx
Excess Vasodilation
Nml or wet
Nml or high
Nml or low
none
Reduce or stop ACEI, Pressors, Vasopressin Inotropes, VAD
Intrinsic Renal Disease/Diuretic Resistance
wet
Nml
Nml
+
High Dose Diuretic, distal tubular diuretic, ultrafiltration
Very High CVP
wet
Nml
Nml
none
High dose diuretics, distal tubular diuretic, ultrafiltration
If his kidney function worsens during Rx, will it be because of: A. Maintenance of ACE inhibitor RX B. Maintenance of of MRA Rx C. Over-diuresis during treatment for acute decompensated heart failure D. Contrast from angiography E. Something specifically the doctor did
Prevalence of Worsening Renal Function During Hospitalization According to Categories of Admission CVP, CI, SBP, and PCWP
Mullens, W. et al. J Am Coll Cardiol 2009;53:589-596
Lets talk about initial treatment- Diuretics high or low dose- plus what else?
A. High dose diuretic (2.5 x oral dose) iv q 12 h and hold ACE/MRA B. High dose by continuous infusion and maintain ACE/MRA C. Standard dose diuretic (1 x oral dose) iv q12 hour and hold ACE/MRA D. Standard dose by continuous infusion and maintain ACE/MRA E. Whatever it takes to get him 2 liters negative and maintain ACE/MRA
DOSE TRIAL Acute Heart Failure (1 symptom AND 1 sign) Home diuretics dose â&#x2030;Ľ 80 mg and â&#x2030;¤240 mg furosemide <24 hours after admission 2x2 factorial randomization High Dose (2.5x oral) Continuous infusion
High Dose (2.5x oral)
Q12 IV bolus
48 hours
Low Dose (1x oral) Continuous infusion
1) Change to oral 2) continue current dose 3) 50% increase in dose 72 hours
Co-Primary endpoints: Change in creatinine from baseline to 72 hours PGA VAS area under curve over 72 hours Felker MG et al, N Engl J Med 2011; 364:797-805
Low Dose (1 x oral) Q12 IV bolus
Change in Creatinine at 72 hours Change in Creatinine (mg/dL)
0.15
p = 0.45
p = 0.21
0.1
0.08
0.07 0.05
0
0.05
0.04
Q12 Continuous Low High Felker MG et al, N Engl J Med 2011; 364:797-805
Trade-off Renal function
Diuretic effect
Preserved RF Optimal diuresis
Worsening RF Optimal diuresis
Preserved RF Suboptimal diuresis
Worsening RF Suboptimal diuresis
Circulation 2001:104:1985-1991
ACEI play a complex role in renal function in HF • May improve CO in some patient and hence increase effective renal perfusion • ACEI may lower BP to the point where effective renal perfusion is impaired • With chronic renal disease, there is hyperfiltration in the remaining nephrons. ACEI decreases efferent arteriole constriction and hence decreases glomerular capillary pressure which may preserve renal function longterm • This may result in a 10-20% increase in creatinine, but over the long term renal function is preserved
The patient continues with his headache and the Doctor: • Holds his MRA • Continues ACE • Starts him on a continuous furosemide drip at 20 mg/hour • Continues beta blocker.
What happens over the next 24 hours? • 2.5 liters of urine output • Shortness of breath improved • Headache improved (due to medicine DR Frank gave him and himself)
• However
creatinine bumps to 2.4 mg/dl, k to 5.0 The next day his urine output slows creatinine is 2.8 and K 5.4
What else could we do? • • • • •
A. Get an Echo B. Serial Troponins C. Serial BNP D. Blood or urine NGAL E. Cardiac Angiography
Approach in Acute Kidney Injury Identification of Risk patients
Primary prevention
Early detection of AKI Reduction of Morbidity and Mortality?
Secondary prevention
“Where are the biomarkers?”
AMI versus AKI Period
Acute Myocardial Infarction
1960s
LDH
1970s
CPK, myoglobin
1980s
CK-MB
1990s
Troponin T
2000s
Troponin I
Multiple Therapies 50% â&#x2020;&#x201C; Mortality
AMI versus AKI Period
Acute Myocardial Infarction
Acute Kidney Injury
1960s
LDH
SCr
1970s
CPK, myoglobin
SCr
1980s
CK-MB
SCr
1990s
Troponin T
SCr
2000s
Troponin I
SCr
Multiple Therapies 50% â&#x2020;&#x201C; Mortality
Supportive Care High Mortality
Need early biomarkers for better treatment of AKI
Cardiac surgery
Heart Failure
Radiocontrast
Trauma
ICU Kidney transplant
NGAL CKD IgA nephropathy
What can NGAL detect?
NGAL
Creatinine
• Marker of Renal Injury • High Sensitivity for Injury • Moderate Specificity for underlying nephropathy
His NGAL (either serum or urine) is 350 ug/ml. What to do? • • • • • •
A. Give high dose diuretic B. Hold ACE C. Hold ARB D.Inotropic agents E.Low dose dopamine F. Ultrafitration
Clinical Scenario: Year 2012
NGAL level
Diagnosis
Intervention
<100 ng/mL
No AKI
Routine care
NGAL level
Diagnosis
Intervention
<100 ng/mL
No renal injury
Routine care
150-300 ng/mL
High risk for AKI
Hold ACE Hold ARB Hold Aldo blockers No contrast No renal toxic antibiotics No NSAIDS Judicious diuretics
NGAL level
Diagnosis
Intervention
<100 ng/mL
No renal injury
Routine care
150-300 ng/mL
High risk for AKI
Hold ACE Hold ARB Hold Aldo blockers No contrast No renal toxic antibiotics No NSAIDS Judicious diuretics
>350 ng/mL
High risk for AKI, dialysis and death
ICU admit Consider ultrafiltration
Find the “sweet spot” of euvolemia before discharge
BNP level
Bnp Bnplow low––but butisisthere therestill still“wet “wet bnp” bnp”around? around? Could Couldyou youhave haveover-diuresed over-diuresed the thepatient? patient?
Begin diuretics
Creatinine
Now Nowyou’ve you’vedonedone-it! it!44more more Days Daysininthe thehospital hospital
NGAL may provide the â&#x20AC;&#x153;sweet spotâ&#x20AC;?
BNP Begin diuretics
N-GAL Creatinine
Stop Stopdiuretics diureticsor oradd add vasodilators vasodilators
Patient course • Day 4 K = 6.2 Kayexalate • Day 6 creatinine 3.6 anuric • Day 7 swan ganz catheter • Day 9- Dialysis • Day 12- Improving Renal function and urine output • Day 15 discharge
Epilogue • The final etiology of his AKI was discovered as patient was leaving. He asked for Dr. Frank for more of that “headache” medicine he gave him in the ED.