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Diagnostic and Therapeutic
Utility of B-Type Natriuretic
Peptide in Patients With
Renal Insufficiency and
Decompensated Heart Failure
Peter A. McCullough, MD, MPH, FACC, FACP, FCCP FAHA,* Kuncheria Joseph, MD,† Vandana S. Mathur, MD‡ *Divisions of Cardiology, Nutrition and Preventive Medicine, William Beaumont Hospital, RoyalOak, MI, †Bon Secours Hospital, Venice, FL, ‡Department of Medicine, Department of Nephrologyand Renal Transplantation, University of California San Francisco, San Francisco, CA Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologicallyand pathophysiologically linked. A recent study in patients with severe CHF demonstratedthat renal plasma flow was inversely correlated with pulmonary capillary wedge pres-sure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction.
This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessingcardiac function and volume status in patients with CKD and examines the safetyand efficacy of BNP therapy in patients with renal insufficiency and decompensatedheart failure. [Rev Cardiovasc Med. 2004;5(1):16-25] Key words: Congestive heart failure • Renin-angiotensin-aldosterone system •
B-type natriuretic peptide • Nesiritide • Chronic kidney disease
Only 16% of chronic kidney disease (CKD) patients who have reached end-stage renal disease (ESRD) have echocardiographically normal leftventricles,1 and 40% have clinically diagnosed congestive heart failure (CHF).2 The activation of the renin-angiotensin-aldosterone system (RAAS),sympathetic nervous system (SNS), and endothelin-1 by heart failure reduces VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE Utility of B-Type Natriuretic Peptide
losclerosis, tubulointerstitial fibrosis, patients with glomerular filtrationrates (GFRs) of 50 mL/min to 75mL/min, 25 mL/min to 50 mL/min, Chronic CHF and CKD may aggravate the progression of each other, leading to an inexorable vicious cycle and accelerated cardiac and renal fibrosis. approximately 30%, 33%, and 49%,respectively. Chronic Kidney Disease and
Congestive Heart Failure
past 15 years.19 According to the U.S.
VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE 17 Utility of B-Type Natriuretic Peptide continued
presentation with acute decompen-sated CHF are typically due to renal Aldosterone
acute CHF. IV diuretics have beenshown to cause significant increases Figure 1. Central role of the renin-angiotensin-aldosterone axis in progressive cardiomyopathy and chronic kidney
disease. CHF, congestive heart failure; CKD, chronic kidney disease; LVH, left ventricular hypertrophy. within 20 minutes of administra-tion.36 Hence, while helpful in clear- ulation is reflected by studies ofpatients with advanced CHF (andmean serum creatinine (Cr) of Hence, while helpful in clearing pulmonary congestion, the early and singular use of IV loop diuretics further activates the RAAS and SNS while leading to elevations in Cr in many patients. from universal (VMAC, 69%15;OPTIME, 69%28). Renal Function as a Predictor
Natriuretic Peptides and Acute
strongest independent predictors ofmortality among U.S. patients whowere hospitalized with a primary Adverse Consequences of Chronic Systemic and
Tissue Level RAAS Activation
60-day hospital readmissions amonga Medicare cohort (N = 2176) with • Coronary atherosclerosis vasoconstriction • Prothrombotic effects/increased plasminogen RAAS, renin-angiotensin-aldosterone system Data from: Epstein M,5 Brewster UC, et al,6 and Hostetter TH, et al.23 VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE Utility of B-Type Natriuretic Peptide
Correlation of Systemic Hemodynamic Parameters to
Renal Plasma Flow in Heart Failure Patients45
epithelial and mesangial cells insmaller quantities.7 Both peptidesagonize the guanylate cyclase-cou- Hemodynamic Parameter
r-value for Correlation With RPF
Renal plasma flow did not correlate significantly with cardiac index, systemic vascular resistance PCWP, pulmonary capillary wedge pressure; PAP, pulmonary artery pressure; RAP, right atrialpressure; RVEF, right ventricular ejection fraction. Data from: Kos, et al.45 BNP, but not ANP.37,38 Both ANP andBNP are cleared by neutral endopep-tidase (NEP 24.11), which is found differences in physiologic response.
VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE 19 Utility of B-Type Natriuretic Peptide continued
Figure 2. (A) Effect of nesiritide
(NES) on urine volumes over 6 hours.
(B) Effect of nesiritide on clinical
by blinded patients (PT) and physi- BNP Levels in Patients With
Physiologic Effects of B-Type Natriuretic Peptide
A number of studies have examined
or Clinical Effect
Known or Presumed Mechanism
Direct inhibition of aldosterone, renin, secondary to improvements in cardiac function and inhibition of endothelin-1, Enhanced potassium secretion secondary 55 to natriuretic effects balanced by aldosterone inhibition Arterial dilatation and potential reflexive VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE Utility of B-Type Natriuretic Peptide
that BNP is not significantly (if at all) reduction in BNP with a dialysis ses-sion may prove to be an importantindicator of optimally reduced left Nesiritide was significantly better at reducing PCWP than placebo plus standard therapies and intravenous nitroglycerin plus standard therapies. Physiologic Effects of BNP
BNP has myriad physiologic and
ics, they either reduce renal filtrationfunction or activate adverse neuro- Hemodynamic Effects of Nesiritide
Hemodynamics and Heart
Nesiritide consistently and rapidly
and pulmonary artery pressures,and it increases cardiac index in a Values are means + SD. P values are for the comparison among all three groups, calculated with the * P < .001 for the pairwise comparison with placebo, by the F test. † P < .05 for the pairwise comparison with placebo, by the F test.
PCWP, pulmonary capillary wedge pressure; RAP, right atrial pressure; SVR, systemic vascular resistance; CI, cardiac index; SBP, systolic blood pressure. VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE 21 Utility of B-Type Natriuretic Peptide continued
even in the absence of urine output.
effects predicts that its use as a natri- conducted. It may be possible, withthe early use of nesiritide in com-bined kidney failure and CHF, to It may be possible, with the early use of nesiritide in combined kidney failure and CHF, to reduce the use of additional therapies, including pies, including inodilators. Thus,the use of additional hospital resources and risks of invasive hemo-dynamic monitoring and arrhyth- Management of Patients With
or GFR occurred (despite natriuresis).
Chronic Kidney Disease and
Natriuresis and Renal
Function Preservation in
VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE Utility of B-Type Natriuretic Peptide
days (10% vs 23%, P = .06), and the > 65, history of sustained ventriculartachycardia, ischemic etiology ofCHF, history of diabetes, outpatient FUSION data suggest that serial outpatient infusions of nesiritide given to patients with advanced heart failure who are at high risk for hospitalization potentially reduces morbidity and mortality due to heart failure. ly infusions of nesiritide in an out-patient setting in patients with VOL. 5 NO. 1 2004 REVIEWS IN CARDIOVASCULAR MEDICINE 23 Utility of B-Type Natriuretic Peptide continued
plasma endothelin-1 levels in patients withdecompensated congestive heart failure. Am J Stevens TL, Burnett JC, Kinoshita M, et al. Afunctional role for endogenous atrial natri- uretic peptide in a canine model of early left ventricular dysfunction. J Clin Invest. 1995;95:1101-1108.
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Unlicensed use of Misoprostol for stillbirth delivery leading to catastrophic brain injury Claimant aged 28 suffered catastrophic brain injury caused by unlicensed use of Misoprostol The NHS Litigation Authority defended the claim until three weeks before the case was due to come to court The Claimant became pregnant in 2004 and was booked for delivery at the West Cumberland