ALLERGY AND IMMUNOLOGY/ELEVATED CREATININE
| UPDATE IN ALLERGY AND IMMUNOLOGY: MYTHS AND FACTS —Katherine Gundling, MD, Associate
Clinical Professor, Division of Allergy and Immunology, University of California, San Francisco,
School of Medicine
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| Myth number 1: patients with shellfish allergy at high risk for allergic reaction to contrast dye
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 | Facts: antigen (allergen) in shellfish is muscle protein tropomyosin (not iodine); tropomyosin triggers—IgE-
mediated immediate hypersensitivity reaction that then causes mast cell degranulation in patients with
allergy to shellfish; contrast dye triggers—non-IgE-mediated reaction (pseudoanaphylactoid or
pseudoanaphylaxis) that causes direct mast cell degranulation
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| Clinical pearl: all atopic patients at slightly higher risk of reacting to contrast dye
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| Gadolinium: silvery white metal (atomic number 64); as intravenous (IV) contrast agent, enhances images in
magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA); adverse reactions
(nonallergic) rare; study findings on allergic reactions—mild (eg, slight itching), 0.016% to 0.017%; moderate
(0.004%-0.017%); severe (eg, anaphylaxis), 0.001% to 0.007%; incidence ≈1 in 10000; potential
problem—Food and Drug Administration (FDA; 2006) reported possible connection between high-dose
gadolinium use during MRA in renal failure patients and nephrogenic systemic fibrosis; dose ≤3 times
higher than in MRI; ≈200 cases reported worldwide (cause and effect not established)
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| Clinical pearls: severe allergic reactions after gadolinium use extremely rare but possible; mechanism unknown;
use caution in patients with renal failure or when using high doses; FDA recommends considering
early hemodialysis after MRA in patients with renal failure
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| For patients with contrast allergy (had allergic reaction to contrast dye in past): avoid contrast if possible; use
contrast agent with lower osmolality; premedication—consider in very atopic patients; prednisone 40 mg,
13, 7, and 1 hr before contrast; diphenhydramine 50 mg intra-muscularly (IM) or po 1 hr before use of contrast;
have emergency care available (including epinephrine) for management of anaphylaxis; more information
at Web site of Joint Council of Allergy, Asthma and Immunology: www.jcaai.org (click on
“Practice Parameters,” then “Anaphylaxis Guidelines”)
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| Myth number 2: bee sting anaphylaxis best treated with prayer (and maybe epinephrine injection)
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| Facts: Hymenoptera include bees and some ants; systemic allergic reactions—diffuse itching; hives; angioedema;
abdominal pain or menstrual-type cramps; asthma or upper airway edema; cardiovascular collapse;
bee stings closer to throat and face more likely to provoke severe respiratory reactions; local
reactions—not usually allergic but local inflammatory reactions
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| Types of bees: yellow jacket; honeybee; wasp; hornet; bumblebee; names of allergens in venom taken from
Latin, eg, for honey bee (Apis mellifera)
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| Cross-reactivity of antigens: greater among yellow jackets and hornets; less cross-reactivity (5%-10%)
among vespids (yellow jackets; wasps; hornets) and honeybees
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| Hymenoptera immunotherapy: desensitization services provided by many allergy and immunology centers;
full desensitization takes ≈5 yr, although most desensitization occurs in first 12 wk of injections (continuing
at 4- to 8-wk intervals); patients with asthma should be well-treated before desensitization; immunotherapy
reduces risk for life-threatening reactions from ≈60% to <2%
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| Clinical pearls: anaphylaxis due to Hymenoptera highly treatable, and appropriate therapy can prevent
death; patients with history of systemic reactions should carry epinephrine injection system and know
how to use it; in patients with severe anaphylactic reactions, check serum tryptase level for possible mastocytosis
(refer to allergist for diagnosis and treatment)
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| Practical tips: avoid wearing brightly colored clothes or strong perfumes; exert caution at outdoor events
where food present; remove nests from around house; when working outdoors, cover exposed areas of skin
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| Myth number 3: chronic urticaria/angioedema usually caused by allergy
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| Facts: if urticaria/angioedema caused by allergy (IgE mediated), trigger usually evident, eg, bee sting
allergy, penicillin or other drug allergy; chronic urticaria/angioedema present when symptoms repeatedly
occur with no obvious precipitant
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| Urticaria/angioedema: chronic defined as >6 wk; triggers for mast cell degranulation include histamine,
tryptase, and many others; basophils also involved in process; urticaria characterized by superficial lesions
(itchy red bumps), angioedema by deeper lesions (hives) without redness; some people get only angioedema,
and not urticaria
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| New developments: 30% to 50% of chronic urticaria/angioedema found to be due to autoantibody; patients
make IgG antibodies to IgE and to IgE receptor on mast cells; recognition of underlying autoimmunity changing
treatment approach; most patients respond to antihistamines (eg, loratadine, 1 tablet per day); for worse
symptoms, fexofenadine (Allegra), 180 mg in morning and cetirizine (Zyrtec) at bedtime; autoimmunity—
look for signs and symptoms of other autoimmune diseases; patients often have thyroid autoantibodies and related
inflammation of thyroid that triggers production of other autoantibodies
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| Clinical pearls: for patients with urticaria/angioedema, no need to work up for hereditary angioedema; new-
onset angioedema in older patient can indicate underlying systemic disease, eg, lymphoproliferative disease
or other immune dysregulation
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| WHAT TO DO ABOUT ELEVATED CREATININE LEVELS— Christina Wyatt, MD, Instructor, Department
of Medicine, Mount Sinai School of Medicine, New York, NY
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| Case example: 62-yr-old woman transferring care; history—hypertension since ≈20 yr of age; hyperlipidemia
(controlled by diet, according to patient); medications—amlodipine (10 mg daily); hydrochlorothiazide (25
mg daily); examination—blood pressure (BP) 148/94 mm Hg; heart rate 78 bpm; weight ≈55 kg; examination
otherwise unremarkable; laboratory results—creatinine 1.6 mg/dL; total cholesterol 246 mg/dL; urine
protein 3+
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| Approach to elevated creatinine: considerations—emergency? acute or chronic? severity of kidney dysfunction?
other evidence of kidney injury? likely causes? emergency—determined by associated laboratory abnormalities
(eg, hyperkalemia, acidosis) not creatinine itself; consider evidence of potentially nephrotoxic
medications; consider chronicity—previous laboratory results; previous diagnosis of kidney disease; in absence
of these, ultrasonography (US) helpful (small kidneys or increased echogenicity potential evidence
of chronic kidney disease)
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| Creatinine and glomerular filtration rate (GFR): creatinine level underestimates severity of kidney disease in
older, smaller, more frail patients; in men, slightly higher creatinine suggests small decrease in GFR;
creatinine—produced by muscle breakdown (endogenous; exogenous animal protein); freely filtered at
glomerulus; also undergoes some tubular secretion (increases as GFR declines; creatinine clearance overestimates
GFR)
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| Formulas: Cockcroft-Gault—estimates creatinine clearance, not GFR; derivation sample (≈260 patients, most
white men); gold standard 24-hr urine creatinine clearance; surrogates for muscle mass (age; sex; weight);
correlates closely with measured GFR at lower ranges and overestimates GFR at higher ranges; Modification
of Diet in Renal Disease (MDRD) Study—derivation sample (≈1600 patients with chronic kidney disease
[CKD]); gold standard GFR measured by iothalamate; surrogates for muscle mass (age; sex; race
[black ethnicity associated with increased muscle mass and filtration rates, including possible increases
in tubular creatinine secretion]); closely correlates with GFR at lower ranges and overestimates
GFR at higher ranges; interpreting laboratory results—most use MDRD equation (weight not
required); many laboratories report GFR <60 mL/min/1.73 m2 and GFR>60 mL/min/1.73 m2 ; choice of
formula—either equation superior to serum creatinine alone for identifying patients with decreased GFR;
physician should select formula he or she more comfortable with or one laboratory uses; neither well validated
in elderly or other types of wasting or loss of muscle mass, eg, HIV infection; drug-dosing guidelines
usually based on Cockcroft-Gault equation; change in serum creatinine at low level, (eg, 1.0 to 1.6 mg/dL)
represents more significant change in GFR than change in creatinine at high level (eg, 5.0 to 6.0 mg/dL)
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| Other evidence of kidney injury: proteinuria—urinal--ysis; for accurate estimate, order urine protein/creatinine
ratio (if not provided by laboratory, order random urine protein and creatinine, put in same units, and divide
protein by creatinine for estimate of grams of protein excreted in urine per day); other urine abnormal--
ities—cells in urine, hematuria; sterile pyuria; glycosuria in absence of significant hyperglycemia (indicates
renal tubular malfunction); abnormal imaging, eg, small kidneys, one small and one normal-sized kidney,
evidence of previous scarring
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| Stages of CKD: based on GFR levels in presence or absence of CKD; stage 1 or 2 (CKD present when GFR <60
mL/min/1.73 m2 ; when GFR >60 mL/min/1.73 m2 , CKD diagnosis requires evidence of kidney injury)
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| Likely comorbidities of CKD: diabetes; hypertension; lupus or other autoimmune disease; viral hepatitis or
HIV infection; nonrenal organ transplant (eg, lung, liver); chronic infection; multiple myeloma
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| Likely medications causing CKD: nonsteoroidal anti-inflammatory drugs or other long-term analgesic use; proton
pump inhibitors; calcineurin inhibitors; antiretroviral agents; lithium
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| Approach to case example: emergency—no; normal electrolytes and volume status; no renally adjusted medication;
no potential nephrotoxins; acute or chronic—no known history of CKD; small echogenic kidneys on
US (suggest ongoing problem); severity of kidney dysfunction—estimated GFR 36 mL/min/1.73 m2 to 40
mL/min/1.73 m2 (stage 3 CKD); other evidence of kidney injury—protein/creatinine ratio 2.9; likely cause—
long-standing hypertension; diagnostic studies—serologies; possible kidney biopsy; management—BP
control; screening for anemia and hyperparathyroidism; cardiovascular risk reduction
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| When to ask for help: unclear diagnosis; stage 4 to 5 CKD (management of complications; planning for dialysis
or transplantation); unexplained changes in creatinine or GFR
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Suggested Reading
Akbari A et al: Detection of chronic kidney disease with laboratory reporting of estimated glomerular filtration
rate and an educational program. Arch Intern Med 164:1788, 2004; Cochran ST et al: Trends in adverse events
after IV administration of contrast media. AJR Am J Roentgenol 176:1385, 2001; Coresh J et al: Kidney function
estimating equations: where do we stand? Curr Opin Nephrol Hypertens 15:276, 2006; Coresh J et al: Prevalence
of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and
Nutrition Examination Survey. Am J Kidney Dis 41:1, 2003; De Ridder F et al: Severe adverse reactions with
contrast agents for magnetic resonance: clinical experience in 30,000 MR examinations. JBR-BTR 84:150,
2001; Enright T et al: The role of a documented allergic profile as a risk factor for radiographic contrast media
reaction. Ann Allergy 62:302, 1989; Gupta P et al: Stinging insect allergy and venom immunotherapy. Allergy
Asthma Proc 25:S9, 2004; Kaplan AP et al: Angioedema. J Am Acad Dermatol 53:373, 2005; Kaplan AP: Chronic
urticaria: pathogenesis and treatment. J Allergy Clin Immunol 114:465, 2004; Levey AS et al: Using standardized
serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular
filtration rate. Ann Intern Med 145:247, 2006; Pedone C et al: Estimating renal function in older people: a comparison
of three formulas. Age Ageing 35:121, 2006; Poggio ED et al: Can we do better than a single estimated
GFR threshold when screening for chronic kidney disease? Kidney Int 72:534, 2007; Rodrigo P et al: Cockroft-
Gault or abbreviated-MDRD equations--which 'weighs' more in cardiovascular risk? Nephrol Dial Transplant
21:2342, 2006; Sheikh A et al: Anaphylaxis. BMJ 331:330, 2005; Stevens LA et al: Assessing kidney function--
measured and estimated glomerular filtration rate. N Engl J Med 354:2473, 2006; Stevens LA et al: Impact of
creatinine calibration on performance of GFR estimating equations in a pooled individual patient database. Am
J Kidney Dis 50:21, 2007.
For information about upcoming meetings
by the sponsors:
University of California, San Francisco, School of Medicine
http://cme.ucsd.edu
Mount Sinai School of Medicine
http://fusion.mssm.edu/cme
Recommended websites:
Joint Council of Allergy, Asthma and Immunology
www.jcaai.org
American Academy of Allergy Asthma and Immunology
www.AAAAI.org
American College of Allergy, Asthma, and Immunology
www.ACAAI.org
Food Allergy and Anaphylaxis Network
www.foodallergy.org
Educational Objectives
| The goal of this program is to improve management of allergy and immunology, and of elevated creatinine
levels. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Prevent allergic reactions to contrast dye agents.
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| 2. Treat patients with bee sting anaphylaxis.
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| 3. Institute therapy for chronic urticaria/angioedema.
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| 4. Diagnose abnormalities underlying elevated creatinine levels.
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| 5. Manage patients with elevated creatinine levels.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care
and not a proprietary business or commercial interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Gundling was recorded at 35th Annual Advances in Internal Medicine, sponsored by the University of California,
San Francisco, School of Medicine on May21-25, 2007, in San Francisco, and Dr. Wyatt at 3rd Annual
Challenges in Internal Medicine, sponsored by the Mount Sinai School of Medicine, on June 20-22, 2007, in
New York, NY. The Audio-Digest Foundation thanks Drs. Gundling and Wyatt and the sponsors for their cooperation
in the production of this program.
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