Intrinsic Acute Renal Failure (ARF)

Home » Intrinsic Acute Renal Failure (ARF) » Overview, Causes, Symptoms, Diagnosis, Treatment, Prognosis (Intrinsic)

Overview

Acute renal failure that is not caused by prerenal or postrenal factors is categorized as intrinsic acute renal failure. This type involves damage or injury within both kidneys. Intrinsic ARF accounts for approximately 40% of the cases of acute renal failure.

The causes can be classified as follows:

• Vascular disease
  • Glomerulonephritis (GN) and vasculitis (inflammation of blood vessels)
  • Renal artery obstruction (atherosclerosis, thrombosis)
  • Renal vein obstruction (thrombosis)
  • TTP-HUS (low blood platelet and red blood cell counts)
• Diseases of tubules and interstitium (space between parts of tissue)
  • Amyloidosis (deposition of proteins in kidney tissues)
  • Interstitial nephritis (associated with allergy or infection)
• Acute tubular necrosis
  • Ischema (lack of blood flow to an organ)
  • Toxins

Nearly 90% of intrinsic ARF cases are caused by ischemia or toxins, both of which lead to acute tubular necrosis (ATN). Ischemic ARF is associated with reduced blood flow to the kidneys (renal hypoperfusion), which leads to tissue death and irreversible kidney failure. Ischemic ARF occurs most frequently when there is hemorrhage (blood loss), trauma, or sepsis (severe infection), and in patients undergoing major cardiovascular surgery.

Many types of medication can cause nephrotoxic intrinsic ARF, and the effect seems to be dose related. Most cases occur in the elderly and in patients with chronic renal failure (CRF). Toxins taken into the body that can trigger intrinsic ARF include the following:

• Antibiotics (e.g., acyclovir, roscarnet)
• Chemotherapeutic drugs (used to treat cancer, e.g., cisplatin, ifosfamide)
• Cyclosporine
• Radiocontrast dyes (used in imaging procedures)

Some toxins are released by tissues as a result of injury or are created by electrolyte imbalance. Some endogenous toxins that trigger nephrotoxic ARF include the following:

• Rhabdomyolysis (release of myoglobin in the urine resulting from the destruction of muscle tissue) caused by the following:
  • Intoxication (e.g., alcohol, cocaine)
  • Seizure
  • Traumatic crush injury
• Hypercalcemia (high level of calcium in the blood) caused by the following:
  • Deposition of calcium in tissue
  • Vasoconstriction (reduced diameter of blood vessels)

Both ischemic and nephrotoxic ARF cause acute tubular necrosis (ATN), but ATN is less pronounced in nephrotoxic ARF.

Allergic interstitial nephritis can be triggered by several different types of drugs. The most common are:

• antibiotics (e.g., penicillin, cephalosporins) and
• nonsteroidal anti-inflammatory drugs (e.g., acetaminophen, ibuprofen).

Signs and Symptoms

• Fever, rash, arthralgia (joint pain)—associated with allergic interstitial nephritis
• Flank pain—associated with renal artery or vein obstruction, severe glomerulonephritis
• Headache, dizziness, confusion, seizure—associated with malignant hypertension
• Oliguria (reduced urination), edema (swelling), hypertension—associated with glomerulonephritis, vasculitis
• Papilledema (swollen optic disk), heart failure—associated with malignant hypertension

Complications
Because excretion of sodium and potassium is impaired, levels of these minerals and the level of chloride in the blood become elevated. This condition is known as metabolic acidosis. Several other complications may occur during the course of intrinsic ARF, including the following:

• Hyperkalmia (high level of potassium in the blood)
• Hypermagnamesia (high level of magnesium in the blood)
• Hyperphosphatemia (high level of phosphates in the blood)
• Hypocalcemia (low level of calcium in the blood)
• Intravascular overload (excess fluid in the vessels due to impaired ability to urinate)
• Uremia (high level of nitrogenous wastes in the blood)

Diagnosis

Diagnosis is based on results from blood tests and urinalysis, and on the patient's medical history and signs and symptoms.

Blood test results that show high levels of creatinine indicate renal ischemia, atheroembolism, or exposure to radiocontrast dye. Severe anemia (low red blood count) may indicate TTP-HUS. Hyperkalemia (high level of potassium), hyperphosphatemia (high level of phosphorous), and hypocalcemia (low level of calcium) occur in rhabdomyolysis.

Urinalysis shows many red and white cells in the urine, and the level of sodium may be high. Proteinuria is a common finding. Mild proteinuria suggests that failure is caused by injured tubules. Moderate proteinuria indicates glomerular injury. Heavy proteinuria occurs in allergic interstitial nephritis.

Renal biopsy is performed when laboratory test results suggest more than one possible cause of intrinsic ARF.

Ultrasound rules out postrenal obstruction (i.e., obstruction in the bladder or urethra) as the cause of symptoms.

Treatment

The goal of treatment for intrinsic ARF is to resolve the underlying cause and its complications.

In nephrotoxic ARF, the toxins are eliminated. In ischemic ARF, adequate blood flow to the kidneys is restored.

Acute glomerulonephritis and vasculitis are treated with glucocorticoids and plasmapheresis (plasma exchange).

In allergic interstitial nephritis, the drug causing the condition is discontinued and glucocortoids are given.

Malignant hypertension is treated with ACE inhibitors to control blood pressure.

Treatment of Complications

• Intravascular overload
  • Salt and water restriction
• Hyponatremia (low sodium level in blood)
  • Water restriction
• Hyperkalemia (high level of potassium in the blood)
  • Dialysis
  • Dietary potassium restriction
  • Sodium bicarbonate
• Metabolic acidosis
  • Dialysis
  • Dietary protein restriction
  • Sodium bicarbonate
• Hyperphosphatemia
  • Dietary phosphate restriction
• Hypocalcemia
  • Calcium carbonate
  • Calcium gluconate
• Hypermagnesemia
  • Discontinuation of magnesium-containing antacids (e.g., Maalox®)

Indications for dialysis include the following:

• Hyperkalemia
• Nonresponsive intravascular overload
• Severe acidosis resistant to other treatments
• Uremia

Prognosis
Mortality rates vary depending on the cause. Approximately 30% of patients with toxin-related intrinsic ARF and approximately 60% of patients with intrinsic ARF as a complication of major cardiovascular surgery die. The prognosis is poor when oliguria is present, in older patients, and in patients with multiple organ failure.

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