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1776 Part XI: Malignant Lymphoid Diseases Chapter 108: Immunoglobulin Light-Chain Amyloidosis 1777

These patients present with the typical four features of the nephrotic
syndrome: (1) nephrotic range proteinuria, (2) hypoalbuminemia,
(3) hyperlipidemia, and (4) edema. Nearly a third of patients with
renal amyloidosis have at least a 1-year history of dramatic elevations
of cholesterol and triglycerides. These are often managed with statin-
type medication and dietary modification without consideration that
a dramatic (>100 mg/dL) rise in cholesterol and triglycerides may be
caused by heavy proteinuria. In the majority of patients, the glomer-
ular filtration rate (GFR) is preserved until sustained proteinuria has
been present for years. Only a small percentage of patients, usually with
interstitial but not glomerular amyloid, present with renal insufficiency
in the absence of heavy proteinuria. 30
The management of the lower-extremity edema is primarily
diuretic therapy. However, excessive diuretic use, particularly in patients
with cardiac amyloidosis, can aggravate already reduced intravascu-
lar volume. Diuretics can also compromise renal blood flow, increase
orthostatic hypotension, and reduce cardiac filling pressures necessary
for adequate cardiac output in patients that have “stiff heart syndrome.”
The threat of continuous proteinuria in amyloidosis is damage to the
tubular system. One-third of patients with renal amyloidosis will ulti-
31
mately require dialysis or renal transplantation. The serum creatinine
level at the time of presentation is the best predictor of which patients
are most likely to require dialysis. Clearly, the best method for preven-
tion of the need for dialysis is effective therapy of the underlying plasma
cell dyscrasia. There are no reported differences between outcomes for
those patients receiving hemodialysis and those receiving peritoneal
dialysis.
In rare instances, patients have profound depression of the serum
albumin below 1 g/dL. These patients often will be disabled by anasarca.
In situations where intractable edema and anasarca makes management
next to impossible, renal ablation has been performed to stop the uri-
nary protein leak, normalize the serum oncotic pressure, and resolve Figure 108–4. Amyloid heart disease. Note thickening of heart walls
the edema. Multiple techniques have been reported, including nephrec- from infiltration. White patches were responsible for the designation
“lardaceous change.”
tomy, ligation of the renal artery, and bilateral ureteral clips. In some
patients, the early initiation of dialysis, even with a normal estimated
GFR, can result in anuria and restoration of normal serum albumin of noncardiac dyspnea. Even when amyloid infiltrates the myocardial
levels. 32 wall and causes it to be thickened, it is often misattributed to hyperten-
The correlation between the amount of amyloid detected and the sive heart disease (hypertrophy) rather than infiltration (Fig. 108–4).
degree of renal dysfunction is poor. The urinary sediment is nonspe- Electrocardiographic abnormalities, including pseudoinfarction and
cific, shows fat and fatty casts, but generally does not contain red cell low voltage, are quite common but are frequently overlooked, whereas
casts. The most common cause of death in patients with renal amy- a pseudoinfarction pattern is misattributed to ischemic heart disease.
loidosis is progressive cardiac dysfunction from infiltrative amyloid The supportive care of patients with cardiac amyloidosis can
cardiomyopathy. be strikingly different from that of ischemic or valvular heart disease.
There is no evidence that afterload reduction with angiotensin-
Heart converting enzyme inhibitors or angiotensin II receptor blockers ben-
Unlike most cardiac disorders, which are caused by a loss of systolic efits patients with relaxation abnormalities, and dyspnea and reduced
function, the restrictive cardiomyopathy caused by amyloid infiltration exercise tolerance frequently increase in patients treated with these
results in poor relaxation (so-called stiff heart syndrome) and poor fill- medications. Fatigue and dyspnea on exertion can also be exacerbated
ing during diastole so that the ventricular chamber has a low end-dia- when β blockers are used for rate or rhythm control.
stolic volume, which results in reduced stroke volume and a reduced In addition to standard echocardiography, accurate diagnosis of
cardiac output. This constitutes a classic example of heart failure with cardiac amyloid requires Doppler flow studies to demonstrate the rapid
preserved systolic function. In fact, the majority of patients with amyloi- decline in velocity of blood inflow into the ventricular chambers and
dosis have an echocardiographically normal ejection fraction until late optimally conducted cardiac strain studies that demonstrate a decline
in the disease. Cardiac amyloid is found in 40 to 50 percent of patients in the rate of fractional shortening of the ventricular chamber. Patients
5
at diagnosis and is responsible for nearly 90 percent of deaths. It is the with unexplained fatigue and/or dyspnea on exertion should have
most challenging syndrome to diagnose because of the lack of speci- immunofixation of the serum and urine and free light-chain testing to
ficity of its symptoms. Fatigue and dyspnea on exertion are often not assess for possible light-chain amyloid. However, even if light chain-
associated with cardiac disease in the presence of amyloid (1) because testing is negative, age related amyloidosis may still be present because
of the lack of radiographic changes of cardiomegaly, pleural effusions, of the deposition of wild-type TTR in the heart. This typically occurs
34
and pulmonary vascular redistribution; (2) because echocardiography in patients older than age 60 years, predominantly men, half of whom
will demonstrate preserved ejection fraction; and (3) because coronary will also have carpal tunnel syndrome. 35,36 Wild-type TTR amyloidosis
33
angiography is invariably normal. This triad often leads to a diagnosis will not be detected by screening for serum and urine light chains, and

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