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Chapter 90: End-Stage Renal Disease

J. Hayes Calvert; David M. Cline

INTRODUCTION AND EPIDEMIOLOGY

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 fatal without some form of renal replacement therapy. At present, renal replacement therapy consists of two basic modalities: renal transplant and dialytic therapy, either hemodialysis or peritoneal dialysis (PD).

Hemodialysis is the initial therapy in the vast majority of new cases of adult ESRD, with a few starting PD and an even smaller number receiving predialytic renal transplants. The proportions are reversed in children, with most children receiving transplants. More than 100,000 Americans await a renal transplant, with a median time of 2.6 years on a transplant wait list.1

One-year mortality for hemodialysis patients is 20% to 25%, with 5-year survival of 35%. Cardiac causes account for about half of all deaths.1 Infections trigger death in up to a quarter of patients, with cerebrovascular events and malignancy being other causes.

PATHOPHYSIOLOGY

Renal failure causes complex physiologic abnormalities (Table 90-1).

TABLE 90-1Clinical Features Associated With Uremia and Dialysis
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TABLE 90-1 Clinical Features Associated With Uremia and Dialysis

General

  • Diffuse muscle cramping, pruritus

Neurologic

  • 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

Cardiovascular

  • 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 tamponade

Hematologic

  • Anemia, decreased red blood cell survival, decreased erythropoietin levels

  • Bleeding diathesis

  • Immunodeficiency (humoral and cellular)

GI

  • Anorexia, metallic taste, nausea, vomiting

  • GI bleeding

  • Diverticulosis, diverticulitis

  • Ascites

Renal bone disease

  • Metastatic calcification (calciphylaxis)

  • Hyperparathyroidism (osteitis fibrosa cystica)

  • Vitamin D3 deficiency and aluminum intoxication (osteomalacia)

Excretory failure leads to elevated levels of >70 chemicals in uremic plasma, and these toxins, individually or in combination, cause uremic organ dysfunction and produce the symptoms of uremia. Besides urea, other potential uremic toxins include cyanate, guanidine, polyamines, and β2-microglobulin.2 If uremia were simply a toxidrome, then dialysis would reverse all its untoward effects; however, it does not, in part because many toxins are highly protein bound and nondialyzable.3 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 ...

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