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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3156_Библиотеки_им_академика_М_И_Перельмана.pdf
TABLE 17.2.1 Evaluation of the Patient with Elevated Aminotransferase
(Continued)
History Physical examination Testing Diagnosis
• Strenuous exercise
• Muscle weakness
or pain
• Creatine kinase
• Aldolase
• Muscular
disorders
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC, complete blood count; Ig,
immunoglobulin; GI, gastrointestinal; RUQ, right upper quadrant; MRI, magnetic resonance imag-
ing; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; TIBC, total iron binding capacity; TSH,
thyroid-stimulating hormone.
REFERENCES
1. Oh RC, Hustead TR. Liver transaminase levels. Am Fam Physician 2011;84(9):1003–1008.
2. Pratt DS, Marshall MK. Evaluation of liver function. In: Longo DL, Fauci AS, Kasper DL, eds.
Harrison’s principles of internal medicine, 18th ed. New York, NY: McGraw-Hill, 2011;2527–2530.
3. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl
J Med 2000;342:1266.
4. Crawford JM. Liver and biliary tract. In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran
pathologic basis of disease, 7th ed. Philadelphia, PA: Elsevier Saunders, 2005;877–937.
5. Cohen JA, Kaplan MM. The SGOT/SGPT ratio an indicator of alcoholic liver disease. Dig Dis Sci
1979;24:835.
I. BACKGROUND. Antinuclear antibodies (ANAs) include antibodies to double-stranded DNA,
histones, chromatin, along with other nuclear proteins and RNA–protein complexes. ANAs are
associated with both systemic and organ-specific autoimmune diseases, use of certain medica-
tions, chronic systemic infections, and rarely malignancy. Due to the low specificity of a positive
ANA titer (50% for all rheumatic diseases), ANA should only be checked when there is clinical
suspicion of a disease process in which the ANA value plays a significant role (1). Five percent
of young adults and 18% of individuals older than 65 years have a mildly elevated ANA and
no disease process (2).
II. PATHOPHYSIOLOGY. ANAs produced in patients with autoimmune connective tissue dis-
ease belong predominantly to the immunoglobulin G class and are generally present at higher
levels. Some ANAs contribute to inflammatory processes by forming immune complexes or
cross-reacting to other antigens. Disease-specific ANA may guide further diagnostic testing
and monitoring; however, clinicians should regard them as a potential indicator of disease and
remember that ANA can be found in many apparently healthy individuals (3,4).
Antinuclear Antibody
Titer, Elevated
Peter F. Cronholm, Rahul Kapur, and
Kristina E. McElhinney
17.3
368
TABLE 17.3.1 Evaluation of the Patient with an Elevated ANA Titer
History Physical examination Further testing Diagnosis
A. Connective tissue disorders
• Fatigue
• Fever
• Weight loss
• Pain, redness, or heat
in two or more joints
• Photosensitivity reaction
• Rash
• Oral ulcers
• Chest pain
• Shortness of breath
• Seizures or psychosis
without history of
offending medications
or drug use
• Abdominal pain
• More common in
women and African
Americans
• Malar rash (presents
in one-third to one-
half of patients)
• Discoid rash
• Joint effusion or
derangement in
chronic disease
(present in two-thirds
of patients)
• Focal neurologic
decits (15% of
patients)
• Pleural effusions
• Cardiac or pleural rubs
• Anti-ds-DNA (high
specicity for SLE)
• Urinalysis with 24-h
collection (look for
persistent proteinuria
or casts)
• CBC (look for
evidence of anemia)
• Specialized nuclear
antigen tests:
ribonucleoprotein,
antibodies to anti-
Smith, anti-SS-A/
Ro, anti-SS-B/
La (patients
with SLE may
produce different
autoantibodies)
• Creatinine (look for
occult renal disease)
• X-rays of involved
joints
• SLE
• Systemic symptoms:
fever, weight loss, and
fatigue
• Morning stiffness
• Chronic, symmetric joint
complaints (three or
more for 6 or more wk)
• Joint symptoms are
often intermittent and
migratory
• ± Red, hot, swollen
joint(s) (most
common are the wrist,
metacarpophalangeal,
or proximal
interphalangeal joints)
• Subcutaneous nodules
(usually on the exten-
sor or pressure sur-
faces)
• Rheumatoid factor
(20% of patients with
RA are negative)
• CBC (look for an
anemia of chronic
disease)
• X-rays of involved
joints (typically
demonstrates
erosions or bone
loss)
• Joint aspiration
(inammatory prole
to synovial uid)
• RA
III. EVALUATION. A careful history and physical examination along with an understanding of the
prevalence of systemic autoimmune diseases should guide the ordering and interpretation of
ANA titers. For further details, see Table 17.3.1.
IV. DIAGNOSIS. See Table 17.3.1.
(Continued)
369
• Excessive dryness of
eyes and/or mouth
• Recurrent oral ulcers
• Sensation disturbance
over the hands and/
or feet
• Vaginal dryness and
dyspareunia
• Dysphagia
• Enlarged salivary
glands
• Dry mucous
membranes
• Decreased salivation
• Decreased tearing
• Purpura
• Peripheral neuropathy
• Anti-SS-A/Ro
• Anti-SS-B/La
• Biopsy of salivary
glands or lip to
assess lymphocytic
inltration
• CBC (look for anemia
of chronic disease)
• Cryoglobulins (if
positive, should
screen for hepatitis C)
• Immunoglobulin
electrophoresis (to
demonstrate a mono-
clonal spike)
• Objective testing
of tear and saliva
production (Schirmer
test and salivary
scintigram)
• Chest X-ray to
differentiate from
possible sarcoidosis
• Sjögren’s
syndrome
• Fever and malaise
• Weight loss
• Muscle tenderness
• Muscle weakness is
usually symmetric,
gradual in onset,
greater loss in lower
limbs
• Skin rash
• Arthralgia
• Chest pain or shortness
of breath with pulmo-
nary involvement
• Muscle strength may
be diminished
• Tenderness to
palpation over affected
areas
• Skin rashes: heliotrope
rash on eyelids or
erythematous papules
over extensor surfaces
of joints (proximal
interphalangeal,
elbow, or knee)
• Presence of anti-U1-
RNP in MCTD
• ANA likely to have
a high titer and a
speckled pattern in
MCTD in contrast to
DM or PM where high
titers are suggestive
of a separate overlap-
ping inammatory
condition
• Muscle biopsy can
be denitive for
diagnosis
• Specic patterns on
electromyelogram
in DM
• Idiopathic inam-
matory myopathy
(e.g., DM, PM)
• MCTD
B. Drugs (More likely to be older and male)
• Procainamide (10%
develop lupus, 50%
have elevated ANAs)
• Symptoms consistent
with SLE described
above
• Anti-histone
antibodies (present
in 95% of cases)
• Drug-induced
lupus
TABLE 17.3.1 Evaluation of the Patient with an Elevated ANA Titer
(Continued)
History Physical examination Further testing Diagnosis
(Continued)
370
• Chlorpromazine
• Quinidine
• Hydralazine symptoms
consistent with SLE
described above
• Erythrocyte
sedimentation rate is
often elevated
• Anti-ds-DNA testing
is usually negative
and can be used
to differentiate this
condition from SLE
• Antibodies
to neutrophil
cytoplasmic antigens
may be positive
C. Systemic illness
• Fever (in 50–80%)
• Malaise
• Weight loss
• Night sweats
• Cough (nonproductive
in early stages,
may eventually be
productive of sputum
and/or blood tinged)
• Pleuritic pain
• Dyspnea
• Extrapulmonary involve-
ment (15% of cases)
• Pleural effusion
• ± Adventitial lung
sounds
• Lymph node enlarge-
ment with or without
tenderness
• Organ-specic ndings
• Tuberculin skin test
• Chest X-ray if positive
skin test
• Acid-fast staining
and culture of
induced sputum for
mycobacteria
• Possibly
bronchoscopy
• CBC looking for
anemia
• Electrolytes may
demonstrate
hyponatremia in
patients complicated
by the syndrome
of inappropri-
ate adrenocortic
hormone secretion
• Tuberculosis
• Fatigue
• Fever
• Chills
• Nonspecic sore throat
• Often normal
• May have
lymphadenopathy
• Joint swelling
• CBC (may
demonstrate
lymphocytosis)
• Viral titers
(Epstein-Barr or cyto-
megalovirus)
• Chronic viral
infections (e.g.,
Epstein-Barr virus
and cytomegalo-
virus)
• Headache
• Sleep disturbances
• Right upper quadrant
tenderness or
liverenlargement
• Other laboratory
abnormalities are
unusual but may
be specic to the
particular viral agent
suspected
TABLE 17.3.1 Evaluation of the Patient with an Elevated ANA Titer
(Continued)
History Physical examination Further testing Diagnosis
(Continued)
371
• Women (95% for PBC
and common for AH)
and young (AH)
• Abdominal pain
• Fever
• Amenorrhea
• Diarrhea
• Pleuritic pain and/or
polyarthritis
• Jaundice
• Hepatomegaly
• Splenomegaly
• Advanced disease
can be characterized
by spider angiomas,
asterixis, palmar
erythema,
caput medusae,
gynecomastia, parotid
enlargement, and
testicular atrophy
• Liver function testing
(AST, ALT, gamma-
glutamyl transferase,
alkaline phospha-
tase)
• Serial testing of
amino-transferases if
elevated
• CBC
• Hepatitis testing
(A, B, and C)
• Anti-ss-DNA
and anti-smooth
muscle antibody
testing
• Anti-mitochondrial
antibodies hallmark
of PBC
• Liver biopsy
• Liver disease
(PBC, AH, and
primary autoim-
mune cholangitis)
• Weight loss
• Fatigue
• Malaise
• Cigarette smoking
• Family history of cancer
• Physical ndings are
dependent on the
type of malignancy
suspected
• Laboratory testing is
dependent on the
type of malignancy
suspected
• Malignancy
(positive ANA is
arare nding) (3)
AH, autoimmune hepatitis; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC,
complete blood count; RNP, antiribonucleoprotein; DM, dermatomyositis; MCTD, mixed connective
tissue disorder; PBC, primary biliary cirrhosis; PM, polymyositis; RA, rheumatoid arthritis; SLE,
systemic lupus erythematosus; ANA, antinuclear antibodies.
TABLE 17.3.1 Evaluation of the Patient with an Elevated ANA Titer
(Continued)
History Physical examination Further testing Diagnosis
REFERENCES
1. Phan TG, Wong RC, Adelstein S. Autoantibodies to extractable nuclear antigens: making detection
and interpretation more meaningful. Clin Diagn Lab Immunol 2002;9:1.
2. Solomon DH, Kavanaugh AJ, Schur PH. Evidence-based guidelines for the use of immunologic tests:
antinuclear antibody testing. Arthritis Rheum 2002;47:434.
3. Lane SK, Gravel JW Jr, Clinical utility of common serum rheumatologic tests. Am Fam Physician
2002;65(6):1073–1080.
4. Wiik AS. Anti-nuclear autoantibodies: clinical utility for diagnosis, prognosis, monitoring, and
planning of treatment strategy in systemic immunoinflammatory diseases. Scand J Rheumatol 2005;34:
260–268.
372
17.4
Brain Natriuretic
Peptide
Perry W. Sexton and Dana McDermott
I. BACKGROUND. Brain natriuretic peptide (BNP) was discovered in the brains of pigs. Human
ventricular cardiomyocytes, stretched from volume or pressure overload, synthesize a peptide
which is cleaved into proBNP. This is secreted and then split into active 32-BNP and inactive
N-terminal proBNP (NT-proBNP) (1). Other known human natriuretic peptides are atrial,
C-type, and dendroaspis.
II. PATHOPHYSIOLOGY. Physiologic levels of BNP cause sodium and water excretion through
the kidneys, although its primary effect is lowering cardiac preload through venous dilation.
It may also inhibit cardiac collagen accumulation and pathologic remodeling, which lead
to progressive heart failure (2). BNP and NT-proBNP are secreted in increasing amounts
as healthy individuals age and more so in women than in men. Natriuretic peptides were
initially used solely in the diagnosis of congestive heart failure (CHF); however, other uses
continue to be established. They are useful in diagnosing, predicting prognosis, and manag-
ing left ventricular dysfunction (LVD) and coronary ischemia. Also, some experts suggest that
these could be used to monitor symptomatic and asymptomatic patients with cardiovascular
risk factors and predict their overall risk of death from cardiovascular events. Recent evidence
suggests that BNP may even have a role in diagnosing and treating children with CHF in
renal disease (3).
III. EVALUATION. Current natriuretic peptide tests are rapid immunofluorescence, which cost
about $29.00 per kit. Within 15 minutes, anti-peptide antibodies bind quantitatively to BNP
or NT-proBNP in the serum and fluoresce proportionally to the amount present. In patients
with CHF and coronary ischemia, the use of rapid bedside tests in the emergency setting has
decreased the morbidity and mortality.
When the clinical diagnosis is unclear, B-type natriuretic peptides offer a way to diagnose
and therapeutically manage CHF and a wide array of other diseases with secondary cardiac
effects. Other factors that may contribute to elevated or decreased levels such as genetics, sex,
age, obesity, exercise, and comorbid medical conditions must also be accounted for when evalu-
ating a patient for possible CHF. Guidelines for using BNP to diagnose and treat new-onset,
acute decompensated, or chronic CHF are listed in Table 17.4.1.
IV. DIAGNOSIS.
A. Congestive Heart Failure.
BNP and NT-proBNP levels are currently used for aid-
ing diagnosis, guiding treatment, and predicting prognosis in CHF. An elevated BNP or
NT-proBNP level is highly sensitive and specific, with 96% and 98% negative predictive
values, respectively, to rule out CHF in the patient with dyspnea (see Table 17.4.1).
1. CHF is usually diagnosed from a detailed history, physical examination, and chest
X-ray. In patients who present with cough or dyspnea, a significantly elevated level can
distinguish a cardiac cause from other differential diagnoses (e.g., pneumonia or asthma).
Adding BNP to the clinical judgment increases the diagnostic accuracy from 74% to
81%. It correlates directly to the New York Heart Association (NYHA) functional class
(i.e., 244–817 pg/mL for classes I–IV) (4) and inversely to cardiac output (5). BNP and
NT-proBNP may be normal at <100 and <300 pg/mL, respectively, whereas most
patients with dyspnea and CHF achieve values >400 and >1,800 pg/mL, respectively
(6,7). Each 100 pg/mL BNP elevation is associated with a 35% increase in risk of cardiac
death (8).
373
TABLE 17.4.1 Helpful Values for BNP
BNP level
(pg/mL)
NT-proBNP
(pg/mL) Interpretation Other
<50 <50
a
Primary care setting NT-proBNP targeted for patients
aged <60 y
<100
b
<300
c, d
CHF improbable
BNP NPV = 96%, NT-proBNP
NPV = 98%
100–400 300–1,800 Possible CHF
BNP > 100 pg/mL has 84.3%
PPV. See text for discussion
of confounding factors. ECHO
recommended for corroboration
>400 >1,800
CHF very probable Patients should be under intense
treatment and monitoring (see
Chapter 7.5)
<500
– Goal hospital
discharge
–
>700
– Severely
decompensated
CHF
–
a
Adjust cutoff for age: <60, 60-75, and >75 y = 50, 100, and 250 pg/mL, respectively.
b
Adjust cutoff <200 pg/mL for patients with atrial brillation (NPV=73%, PPV=85%).
c
Adjust cutoff for age: <50, 50 to 75, and >75 y = 450, 900, and 1,800 pg/mL, respectively
(PPV=90% and NPV=84%).
d
Adjust cutoff <1200 pg/mL for patients presenting with eGFR <60 mL/min/1.73 m
2
.
Key: BNP, brain natriuretic peptide; NT-proBNP, N-terminal propeptide BNP; CHF, congestive
heart failure; NPV, negative predictive value; PPV, positive predictive value; ECHO, echocardiogram;
eGFR, estimated glomerular ltration rate.
2. BNP and NT-proBNP levels usually fall after effective therapeutic intervention. A half-
life is only 22 minutes; therefore, serial testing can be informative and aid in titrating
therapy (9,10). Morbidity, mortality, and hospital readmission rates are dependent on
aggressive treatment of CHF, and a decline in these levels often correlate with clini-
cal improvements. A suggested goal is a BNP < 500 pg/nL at hospital discharge and
<50 pg/nL in outpatient primary care settings (11).
3. A persistently elevated BNP or NT-proBNP despite optimal medical intervention car-
ries a worse prognosis. Patients with chronic CHF may have persistent elevations and be
clinically stable. Though they can provide useful prognostic information at initial clinical
presentation, a series of levels is often more valuable for interpreting the relative trend in
a particular patient.
B. Left Ventricular Dysfunction
1. Elevated BNP and NT-proBNP levels can predict the existence and severity of LVD
in both symptomatic and asymptomatic patients (12). Some authors even suggest that
levels can be used as a screening test for LVD in patients with cardiovascular risk factors.
Of note, NT-proBNP concentrations rise four times higher than BNP in LVD and may
prove to be more sensitive for diagnosing and treating this condition (13).
374
2. Elevations correlate with LV mass (i.e., hypertrophy) and LV distension and right
ventricular (12), intra-ventricular, and pulmonary pressures (5); thus, other conditions
(e.g., primary pulmonary hypertension, pulmonary embolism, primary hyperaldoste-
ronism, Cushing’s syndrome, athletic heart, or restrictive cardiomyopathy) may pre-
cipitate and lead to relative increases. Consequently, levels also reflect the ventricular
and atrial consequences of mitral regurgitation (14) and the severity of aortic stenosis
(15). They even increase as LVD worsens in severe sepsis despite preservation of ejection
fraction (16).
C. Acute Coronary Syndromes and Known Coronary Ischemia. In the patient present-
ing with chest pain and questionable coronary ischemia, BNP and NT-proBNP may be
elevated, denoting ongoing or recent ischemia if measured 6 hours to 10 days after an event.
NT-proBNP has shown to have a stronger correlation with cardiovascular mortality than
Troponin-C and C-reactive protein markers in cardiac ischemia (17). This can be especially
helpful in patients who have nonspecific ST-T wave changes, a non-q wave myocardial
infarction, or atypical chest pain. It is not yet known whether BNP predicts the severity or
ultimately the prognosis of cardiac ischemia in these populations (18).
D. Special Considerations
1. Genetics, obesity, and age play a significant role in the variation of BNP and NT-proBNP
among patients. In fact, genetic factors may account for almost half of the total variation
(19). African American and Hispanic patients have higher levels than Caucasians within
the same NYHA class (20). Exercise alone can decrease their levels by about 30% (21).
Obese patients (i.e., body mass index >30) with CHF tend to have lower levels (22).
Normally women and older individuals have higher levels. Optimal plasma NT-proBNP
cutoffs for ruling in CHF when accounting for ages <50, 50–75, and >75 correspond
to 450, 900, and 1800 pg/mL, respectively (7).
2. BNP and NT-proBNP can be elevated in cirrhosis, renal disease, anemia (23), and
cardio-renal syndrome (24). Patients with cirrhosis have levels three times those of
healthy subjects in some studies. Patients with dialysis-dependent renal failure have
unreliable levels, likely resulting from chronic volume expansion. However, patients
with nondialysis-dependent renal dysfunction have levels that reliably correlate with
echocardiographic evidence of CHF. The estimated glomerular filtration rate (eGFR) is
inversely related to concentrations, and thus, for patients presenting with dyspnea and
an eGFR < 60 mL/min/1.73 m
2
, an NT-proBNP > 1,200 pg/mL indicates that CHF
is probable (25).
3. Any type of cardiac inflammation, including cardiac transplant rejection, Kawasaki
disease, constrictive pericarditis (26), or an arrhythmogenic ventricle with decreased
ejection fraction, may lead to increased levels. Specifically, atrial fibrillation is associ-
ated with higher levels in the absence of CHF (13), and 200 pg/mL has been a proposed
cutoff (27).
4. Other potential uses of BNP are being studied and developed, including nesiritide (i.e.,
recombinant BNP) to treat CHF, but recent studies show that in acute decompensated
CHF, nesiritide therapy did not significantly change dyspnea, mortality, or 30-day
hospital readmission rates (28, 29).
REFERENCES
1. Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998;339:321–328.
2.
Tamura N, Ogawa Y, Chusho H, et al. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc
Natl Acad Sci U S A 2000;97:4239.
3.
Wieczorek SJ, Wu AH, Christenson R, et al. A rapid B-type natriuretic peptide assay accurately diag-
noses left ventricular dysfunction and heart failure: a multicenter evaluation. Am Heart J 2002;144:834.
4.
Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in
the emergency diagnosis of heart failure. N Engl J Med 2002;347:161.
5. Silver MA, Maisel A, Yancy CW, et al. BNP Consensus Panel 2004: A clinical approach for the diag-
nostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in
cardiovascular diseases. Congest Heart Fail 2004;10(5 Suppl 3):1–30.
375
6. Hobbs RE. Using BNP to diagnose, manage, and treat heart failure. Cleve Clin J Med 2003;70(4):
333–336.
7. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide levels in
heart failure. J Am Coll Cardiol 2004;43:1590.
8. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death
and cardiac events in patients with heart failure: systematic review. BMJ 2005;330:625.
9. McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment
in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) multinational
study. Circulation 2002;106:416–422.
10. Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriuretic peptide-guided therapy to improve
outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol 2007;49:1733.
11. Cowie MR, O’Collinson P, Dargie H, et al. Recommendations on the clinical use of B-type natri-
uretic peptide testing (BNP or NTproBNP) in the UK and Ireland. Br J Cardiol 2010;17:76–80.
12. Palazzuoli A, Gallotta M, Quatrini I, Nuti R. Natriuretic peptides (BNP and NT-proBNP): measure-
ment and relevance in heart failure. Vasc Health Risk Manage 2010;6:411–418.
13. Hunt PJ, Richards AM, Nicholls MG, et al. Immunoreactive amino-terminal pro-brain natriuretic
peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf) 1997;47:287.
14. Yusoff R, Clayton N, Keevil B, et al. Utility of plasma N-terminal brain natriuretic peptide as a
marker of functional capacity in patients with chronic severe mitral regurgitation. Am J Cardiol
2006;97:1498.
15. Gerber IL, Stewart RA, Legget ME, et al. Increased plasma natriuretic peptide levels reflect symptom
onset in aortic stenosis. Circulation 2003;107:1884.
16. Koglin J, Pehlivani S, Schwaiblmair M, et al. Role of brain natriuretic peptide in risk stratification of
patients with congestive heart failure. J Am Coll Cardiol 2001;38:1934.
17. James SK, Lindahl B, Siegbahn A, et al. N-terminal pro-brain natriuretic peptide and other risk
markers for the separate prediction of mortality and subsequent myocardial infarction in patients
with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries
(GUSTO)-IV substudy. Circulation 2003;108:275.
18. De Lemos JA, Morrow DA, Bentley JH, et al. The prognostic value of B-type natriuretic peptide in
patients with acute coronary syndromes. N Engl J Med 2001;345:1014.
19. Wang TJ, Larson MG, Levy D, et al. Heritability and genetic linkage of plasma natriuretic peptide
levels. Circulation 2003;108:13.
20. Daniels LB, Bhalla V, Clopton P, et al. B-type natriuretic peptide (BNP) levels and ethnic disparities
in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure
Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision
making in patients presenting with shortness of breath. J Cardiac Fail 2006;12:281–228.
21. Passino C, Severino S, Poletti R, et al. Aerobic training decreases B-type natriuretic peptide expression
and adrenergic activation in patients with heart failure. J Am Coll Cardiol 2006;47:1835.
22. Das SR, Drazner MH, Dries DL, et al. Impact of body mass and body composition on circulating
levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 2005;112:2163.
23. Wu AH, Omland T, Wold Knudsen C. Breathing Not Properly Multinational Study Investigations
Relationship of B-type natriuretic peptide and anemia in patients with and without heart failure:
a substudy from the Breathing Not Properly (BNP) Multinational Study. Am J Hematol 2005;80:
174–180.
24.
Palazzuoli A, Silverberg DS, Iovine F, et al. Effects of beta-erythropoietin treatment on left ventricular
remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal
anemia syndrome. Am Heart J 2007;154:645.e9–e15.
25. Anwaruddin S, Lloyd-Jones DM, Baggish A, et al. Renal function, congestive heart failure, and
amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of
Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol 2006;47:91.
26. Leya FS, Arab D, Joyal D, et al. The efficacy of brain natriuretic peptide levels in differentiating
constrictive pericarditis from restrictive cardiomyopathy. J Am Coll Cardiol 2005;45:1900.
27.
Knudsen CW, Omland T, Clopton P, et al. Impact of atrial fibrillation on the diagnostic performance
of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the breathing not
properly multinational study. J Am Coll Cardiol 2005;46:838.
29. O Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decom-
pensated heart failure. N Engl J Med 2011;365:32–43.
376
17.5
Elevated Creatinine
Nathan Falk and Aaron Goodrich
I. BACKGROUND. Elevated creatinine is defined as a serum creatinine >1.2 mg/dL in males
and >1.1 mg/dL in females (1). Creatinine is the breakdown product of creatine from muscle
metabolism and is excreted in the urine. The main use of creatinine is as a measure of kidney
function by calculating the glomerular filtration rate.
II. PATHOPHYSIOLOGY. Elevated creatinine is due to renal insufficiency and can be divided into
three etiologic groups: prerenal, intrinsic renal disease, and postrenal. These can also be broken
down into acute (days to weeks) and chronic (months to years) causes. Acute kidney injury is
defined as an acute rise in creatinine greater than 0.5 mg/dL above baseline or greater than 1.5-
fold above baseline or oliguria (urine output less than 400 mL/d). (2) Prerenal causes account
for 60–70% of cases and include decreased perfusion of the kidneys from either absolute or
relative dehydration or decreased intravascular volume. Intrinsic causes account for 25–40% of
cases and can be further broken down into vascular diseases, glomerular diseases, and tubuloint-
erstitial diseases. Postrenal causes account for 5–10% of cases and are caused by any obstruction
between the kidney and the end of the ureter (3). Falsely elevated creatinine can occur due to
medications that interfere with assay technique (cefoxitin or other cephalosporins, flucytosine,
methyldopa, levodopa, vitamin C, and barbiturates), medications that block tubular excretion
of creatinine (cimetidine, pyrimethamine, and trimethoprim), toxin ingestion (methanol and
isopropyl alcohol), creatine supplementation, and ketoacidosis (1).
III. EVALUATION. See Tables 17.5.1–17.5.3. Creatinine should be monitored in patients with
certain chronic medical conditions (diabetes, hypertension, etc.) and certain medications
(angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs),
diuretics, etc.). Almost all admissions to the hospital should have creatinine evaluated and
should be monitored daily in patients receiving treatments known to effect creatinine (IV fluids,
nephrotoxic antibiotics, and diuretics).
TABLE 17.5.1 Acute vs. Chronic Renal Failure
Acute Chronic
Hypovolemia
Sepsis
Acute hypertension
Fever
Hematuria
History of taking nephrotoxic agents
No anemia
No hypocalcemia
No hyperphosphatemia
History of CKD
Previously elevated creatinine in records
Normochromic normocytic anemia
Hypocalcemia
Hyperphosphatemia
Atrophic kidneys
CKD, chronic kidney disease.
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