Download Gadolinium

KIDNEY
DISEASE
AND
GADOLINIUM:
IS THERE A LINK?
Nephrogenic
Systemic Fibrosis
New Disease.
All Should Know.
Nephrogenic Systemic Fibrosis
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1.
2.
Nephrogenic systemic fibrosis (NSF) is a
recently identified fibrosing disorder seen
only in patient with kidney failure.
It is characterized by two primary features
Thickening and hardening of the skin overlying
the extermities and trunk.
Marked expansion and fibrosis of the dermis in
association with CD34-positive fibrocytes.
Terminology
1.
Nephrogenic fibrosing dermopath (NFD)
2.
Dialysis – associated systemic fibrosis
Epidemiology
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NSF occurs exclusively in patients with
kidney failure.
The first cases were noted between
1997 and 2000.
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No Predilection to NSF by gender,
race, or age, etiology of kidney disease
or duration of renal failure.
Peritoneal dialysis, May be at Higher
risk than hemodialysis.
Etiology


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A retrospective analysis of two large tissue
repositories failed to identify any cases
presenting before 1997.
A case matched study undertaken by the centers
for disease control failed to isolate a single
mediator (drug, medical technique, chemical or
infectious agent) that could explain every case of
NSF.
Increasing epidemlologic evidence has implicated
gadolinium-containing contrast agents.
Gadolinium
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Gadolinium chelaes are excreted unchanged
exclusively by the kidney.
Its half-life is 1.3hours in healthy.
10 hours at an estimated. (GFR) of 20 to 40
ML/min.
34 hours in patients with end-stage renal disease.
1.9 to 2.6 hours if hemodialysis follows the
administration of gadolinium
Risk
1.
2.
Dose-response relationship
exists.
Erythropoietin therapy
Clinical Manifestations


The latent period between exposure
and disease onset is usually two to four
weeks.
The range is as short as two days and
as long as 18 moths
Skin involvement
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Skin disease in NSF symmetrical.
Bilateral fibrotic indurated papules,
plaques.
Subcutaneous nodules may be
erythematous.
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The lesions first develop on the lower
legs, ankles, feet, wrist, hand.
Common distribution patterns involve
the ankles up to mid-thighs.
Skin between the wrists and mid-upper
arms, bilaterally.
Unusual distribution patterns overlying
the mid and lower abdomen.

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The head is spared.
The lesion preceded by edema and may
initially be misdiagnosed as cellulitis.
The edema usually resolves and skin
retains a thickened and firm texture.
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The skin may have a cobblestone
woody or peau d’ orange appearance.
The lesions may be pruritic and sharp
pain or a burning sensation.
Movement of the joints may be so
limited and flexibility is lost.
Systemic involvement

Movement of the joints may be so limited
and flexibility is lost.

Muscle induration but strength is normal joint
contractures.
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Fibrosis of internal organs, diaphragm ,
myocardium, pericardium and pleura and
dura mater.
Yellow asymptoatic scleral plaques similar to
pinguicula.
Diagnosis
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Marked ESR and CRP
Histopathologic examination of a
biopsy.
Biopsy
1.
2.
Light microscopy varies with disease
severity, ranging from proliferation of
dermal fibrocytes in early lesions, to
marked thickening of the dermis with
florid proliferation of fibrocytes with
long dendritic processes in fully
developed cases.
Associated with histiocytes and factor
XIIIa+drmal dendritic cells
3. Thick collagen bundles with
surrounding clefts are a prominent
finding.
4. Immunohistochemical staining reveals.
CD34+dermal cells, with the dendritic
processes.
5. Elastic fibers and around collagen
bundles in a dense network
6. Increased number of CD68+and factor
XIII+dendritic cells
7. Special tasting may reveal gadolinium.
Laboratory tests
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Elevations in serum C-reactive protein,
serum ferritin, reduction in serum
albumin
Normal or absent are the eosinophil
count, serum and urine protein
electrophoresis, thyroid function tests
are normal.
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Pulmonary function tests reveal
reductions in total lung capacity and
volume and diffusing capacity.
Echocardiography is suggested possible
cardiomyopathy.
Muscle biopsy
Differential Diagnosis
1.
Scleroderma
2.
Scleromyxedema
3.
Eosinophilic
4.
Calciphylaxis
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In a review of the published literature,
1.
28% of patients had no improvement
2.
3.
28% of patients died
20% had modest improvement
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Improvement in or remission of NSF
has been described, primarlly in
patients who recovered renal funtion.
1.
Prevention
2.
Avoidance of gadolinium
1.
2.
3.
Gadolinium at high doses should be
used only if clearly necessary
Should be avoided in patients with a
diagnosis or clinical suspicion of NSF.
Institute prompt hemodialysis after
the imaging study if gadolinium is
given
4. the average rates of gadolinium removal
were 78, 96, and 99 percent in the first,
second, and third every –other-day dialysis
sessions respectively
5. No evidence that hemodialysis immediately
after exposure lowers the risk or severity of
NSF.
6. Gadolinium is cleared much more slowly
with peritoneal dialysis hemodialysis after
the procedure is advisable.
Treatment
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1.
2.
No proven therapy for NSF other than
recovery of renal function.
Intensive physical therapy is
recommended in all patients to
prevent or reverse disability
Renal transplantation
3. Extracorporeal photopheresis
4. Ultraviolet A phototherapy
5. Plasmapheresis
6. Other modalities photodynamic
therapy, pentoxifylline, sodium
thiosulfate, intravenous immune
globulin.