1122
UNIT X
Disorders of Renal Function and Fluids and Electrolytes
parathyroid gland with medication such as the calcimimetic
agent cinacalcet.
28
However, because adynamic bone disease
is often a consequence of overzealous treatment of secondary
hyperthyroidism, these agents require careful use.
Hematologic Disorders
Anemia.
Chronic anemia (hemoglobin levels <13.5 g/dL
in adult men and <12 g/dL in adult women) is the most
profound hematologic alteration that accompanies CKD.
21
African Americans and people with diabetes have even higher
rates of anemia for each advanced stage of CKD.
28
The NKF
guidelines recommend that those people with a GFR less than
60mL/min/1.73m
2
should be evaluated for anemia.Assessment
for anemia and its causes includes measures of hemoglobin,
hematocrit, and iron stores.
The anemia of CKD is due to several factors, includ-
ing chronic blood loss, hemolysis, bone marrow suppres-
sion due to retained uremic factors, and decreased red cell
production due to impaired production of erythropoietin and
iron deficiency. The kidneys are the primary site for the pro-
duction of the hormone
erythropoietin,
which controls red
blood cell production.
21
In renal failure, erythropoietin pro-
duction usually is insufficient to stimulate adequate red blood
cell production by the bone marrow. Among the causes of
iron deficiency in people with CKD are anorexia and dietary
restrictions that limit intake, and the blood loss that occurs
during dialysis.
21
When untreated, anemia causes or contributes to weak-
ness, fatigue, depression, insomnia, and decreased cognitive
function. There also is an increasing concern regarding the
physiologic effects of anemia on cardiovascular function.
2
The
anemia of renal failure produces a decrease in blood viscos-
ity and a compensatory increase in heart rate. The decreased
blood viscosity also exacerbates peripheral vasodilation and
contributes to decreased vascular resistance. Cardiac output
increases in a compensatory fashion to maintain tissue perfu-
sion. Anemia also limits myocardial oxygen supply, particu-
larly in people with coronary heart disease, leading to angina
pectoris and other ischemic events.
29
Mr. Reterez
has severe fatigue probably due to
a low hematocrit and hemoglobin secondary to
his CKD, which occurred due to his polycystic
kidney disease. This is anemia of chronic disease. Most
likely, Mr. Reterez will be put on an erythropoietin supple-
ment to assist in triggering his bone marrow to reproduce
more red blood cells. He will also be carefully checked by
his primary care provider for signs of cardiovascular dis-
ease and also managed for hypertension since his blood
pressure is 145/92 and his pulse is 92.
A significant advance in medical management of CKD
was realized when recombinant human erythropoietin (rhEPO)
became available in 1989 to help maintain hematocrit levels
in people with kidney failure.
2
One erythropoiesis-stimulating
protein with a prolonged half-life was introduced for treatment
of anemia in CKD about 3 years ago. It is darbepoetin alfa, a
hyperglycosylated analog of rhEPO.
30
However, evidence sug-
gests it is no more effective, but is more expensive for people
with CKD on dialysis than epoetin alfa.
31
Secondary benefits
of treating anemia with rhEPO, previously attributed to the
correction of uremia, include improvement in appetite, energy
level, sexual function, skin color, and hair and nail growth,
and reduced cold intolerance. Because worsening of hyper-
tension and seizures have occurred when the hematocrit was
raised too suddenly, frequent measurements of hematocrit are
necessary. Additionally, currently researchers are question-
ing if erythropoietin-stimulating agents are as effective as
once thought or if they are actually toxic.
32
More evidence
is needed to validate whether the erythropoietin-stimulating
agents should be used or not.
32
Coagulopathies.
Bleeding disorders are manifested by epi-
staxis, menorrhagia, gastrointestinal bleeding, and bruising of
the skin and subcutaneous tissues. Although platelet produc-
tion often is normal in CKD, platelet function is impaired.
6,17
Coagulative function improves with dialysis but does not
completely normalize, suggesting that uremia contributes to
the problem. People with CKD also have greater susceptibility
to thrombotic disorders.
Cardiovascular Disorders
The overall mortality rate from cardiovascular disease in peo-
ple with CKD is many times that of the general population.
29
Even after stratification for age, the incidence of cardiovascu-
lar disease remains 10 to 20 times higher in people with CKD
than in the general population.
29
Hypertension.
Hypertension commonly is an early manifes-
tation of CKD. The mechanisms that produce hypertension in
CKD are multifactorial. They include an increased vascular
volume, elevation of peripheral vascular resistance, decreased
levels of renal vasodilator prostaglandins, and increased activ-
ity of the renin–angiotensin system.
Early identification and aggressive treatment of hyper-
tension has been shown to slow the progression of renal
impairment in many types of kidney disease.
2,32
Treatment
involves salt and water restriction and the use of antihyper-
tensive medications to control blood pressure. Many people
with CKD need to take several antihypertensive medications
to control blood pressure. There is a new class of hyperten-
sion drugs called endothelin blockers. These drugs are being
trialed in people with difficult-to-manage hypertension.
33
Heart Disease.
The spectrum of cardiovascular disease due to
CKD includes left ventricular hypertrophy and ischemic heart
disease. People with CKD tend to have an increased preva-
lence of left ventricular dysfunction, with both depressed left
ventricular ejection fraction, as in systolic dysfunction, and
impaired ventricular filling, as in diastolic failure.
2
Multiple
factors lead to development of left ventricular dysfunction,
including extracellular fluid overload, shunting of blood
