End-stage renal disease (ESRD) is the irreversible loss of renal
function, resulting in the accumulation of toxins and the loss of
internal homeostasis. Uremia, the clinical syndrome resulting from
ESRD, is universally fatal without some form of renal replacement
therapy. At present, renal replacement therapy consists of two basic
modalities: renal transplant and dialysis.
This chapter discusses the pathophysiology and clinical features
of uremia and the specific techniques and complications related
to hemodialysis and peritoneal dialysis (PD).
According to the 2005 annual report of the United States Renal
Data System, >350,000 patients with ESRD are being treated by dialysis,
with approximately 92% receiving hemodialysis and about
8% on continuous ambulatory PD (CAPD).1 ESRD
is a disease of the elderly, with patients >65 years of age comprising
47.9% of new cases of ESRD and accounting for 37.2% of
all living patients with ESRD. Diabetes mellitus is the most common
disease responsible for ESRD (42.8%), followed by hypertension
(25.9%), glomerulonephritis (9.0%), cystic kidney
disease (2.3%), and other causes (20.0%). The
United States Renal Data System projects a 6% to 7% growth
per year in the incidence of ESRD. An increasing incidence and life
span will result in an expected rising prevalence of ESRD of 8% to
9% per year.
Of those receiving renal replacement therapy for ESRD, 70% are
undergoing dialysis therapy and 30% have received renal
transplants. Children (aged 0 to 19 years) have higher rates of
renal transplantation (77.7%) and PD (12.1%) than
do other age groups. The 1-, 2-, and 5-year survival rates (adjusted
for age, race, sex, and primary disease) for individuals with ESRD
are 79.6%, 64.9%, and 34.4%, respectively.
Cardiac causes account for approximately 50% of all deaths
in patients with ESRD. Infectious causes of death are seen in 10% to
25% of patients. Cerebrovascular events make up 6% of
deaths in ESRD, with malignancy accounting for another 1% to
4%. Approximately 20% of dialysis patients withdraw from
therapy before death. Patients >65 years of age have the highest withdrawal
rate (25%), which is linked to an increasing severity of
comorbid conditions affecting patients’ quality of life
on renal replacement therapy.
Uremia, contamination of the blood with urine,
is the term used to describe the clinical syndrome resulting from
ESRD. Azotemia is the buildup of nitrogen in the
Excretory failure leads to elevated levels of
>70 chemicals in uremic plasma, which gives rise to the hypothesis
that these toxins, individually or in combination, cause uremic
organ dysfunction and produce the symptoms of uremia. Limiting protein
intake markedly improves the symptoms of uremia. Urea, the major
breakdown product of proteins, reproduces a few of the neurobehavioral
uremic symptoms, but only at very high concentrations. Other potential
uremic toxins include cyanate, guanidine, polyamines, and β2-microglobulin.
The toxins accumulating in ESRD excretory failure do not explain
all its clinical features. In addition, if uremia were simply a
toxidrome, then dialysis would reverse all its untoward effects.
Because many uremia-related organ dysfunctions persist after dialysis,
other processes are clearly important.
Biosynthetic failure refers to the aspects of
uremia caused by loss of the renal hormones 1,25(OH)2-vitamin D3 and erythropoietin. The kidneys are primarily responsible
for the secretion of erythropoietin and 1α-hydroxylase,
which is necessary to produce the active form of vitamin D3.
Because 85% of erythropoietin is produced in the kidneys,
ESRD patients have depressed levels of erythropoietin, which contributes
to anemia. Vitamin D3 deficiency results in decreased GI
calcium absorption, inducing secondary hyperparathyroidism, which
is responsible for the development of renal bone disease.
Regulatory failure results in an oversecretion
of hormones, leading to uremia by disruption of normal feedback
mechanisms. The maintenance of internal homeostasis depends on a
variety of extrarenal processes. These homeostatic responses, although
adaptive to one toxin, may have untoward effects outside the system
they are attempting to regulate.
The uremic state produces excess free oxygen radicals, which
react with carbohydrates, lipids, and amino acids to create advanced
glycation end products, which have been linked to atherosclerosis
and amyloidosis in ESRD patients.2 Unfortunately,
glycation end products are largely protein bound and are not cleared
by dialysis, which may explain the progressive nature of the atherosclerosis
and amyloidosis seen in ESRD patients.3
Uremia is a clinical syndrome, and no single symptom, sign, or
laboratory test result reflects all aspects of uremia. Although
a correlation exists between the symptoms of uremia and low glomerular
filtration rate (8 to 10 mL/min/1.73 m2),
blood urea nitrogen and serum creatinine levels are inaccurate markers
of the clinical syndrome of uremia. The decision to start long-term
dialysis is a clinical one based on the severity of the patient’s
symptoms related to uremia (Table 93-1).
The most common reasons for emergency dialysis are hyperkalemia,
severe acid-base disturbances, and pulmonary edema resistant to
93-1 Clinical Features of Uremia and Dialysis
| Save Table
93-1 Clinical Features of Uremia and Dialysis
|Uremic encephalopathy: cognitive defects, memory
loss, decreased attentiveness, slurred speech, reversal of sleep-wake
cycle, asterixis, seizure, coma, symptomatic improvement with dialysis|
|Dialysis dementia: progressive neurologic decline,
failure to improve with dialysis, fatal|
|Subdural hematoma: headache, focal neurologic
deficits, seizure, coma|
|Peripheral neuropathy: singultus (hiccups),
restless leg syndrome, sensorimotor neuropathy, autonomic neuropathy|
|Coronary artery disease|
|Hypertension: essential hypertension, glomerulonephritis,
renal artery stenosis, fluid overload|
|Heart failure: fluid overload, uremic cardiomyopathy,
high-output arteriovenous fistula|
|Pericarditis: uremic, dialysis related, pericardial
|Anemia, decreased red blood cell survival, decreased
|Immunodeficiency (humoral and cellular)|
|Anorexia, metallic taste, nausea, vomiting|
|Renal bone disease|
|Metastatic calcification (calciphylaxis)|
|Hyperparathyroidism (osteitis ...|
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