Renal Failure

Diseases of tubules and interstitial: (space between the cells) space.

1. Amyloidosis (deposition of proteins in kidney tissues)
2. Interstitial nephritis (associated with allergy or infection)

Acute tubular necrosis: The patho physiology of acute tubular necrosis is not clearly understood but it is generally believed that there are two main causes of tubular necrosis. Research shows that Ischemia and toxins cause close to 90 % of all intrinsic ARF. Both these conditions lead to Acute Tubular Necrosis, often abbreviated to ATN.

1. Ischemia: Due to the lack of oxygenated blood. This occurs when there is hemorrhage (blood loss / bleeding), trauma, or sepsis from severe infections. These conditions may also occur in patients who are undergoing major cardiovascular surgery.
2. Toxins: These are poisons which destroy the nephritic tubules. These can be sub categorized into endogenous or exogenous. Some toxins are the result of injury and others are created by electrolyte imbalances.

• Antibiotics like acyclovir, (roscarnet) used to treat infections
• Chemotherapeutic drugs (used to treat cancer, e.g., cisplatin, ifosfamide)
• Cyclosporine is medication which is used with other medications to prevent transplant rejection, most frequently for people who have received kidney, liver, and heart transplants
• Radiocontrast dyes used for x-ray imaging procedures

Some endogenous poisons which cause nephrotoxic ARF include the following:

1. Rhabdomyolysis: During this condition toxins are released into the circulatory system which harm the kidneys. Generally, toxins are produced form destroyed muscle cells. An pigment that contains Iron, called myoglobin that exists in skeletal muscle enters the bloodstream after the muscle suffers damage. The primary muscle damage may be due to traumatic crush injury or from viral infections. Some may result from toxic reaction to prescription and nonprescription medications.
2. Intoxication with alcohol, cocaine etc
3. Seizures
4. Traumatic crush injury, see Rhabdomyolysis above
5. Hypercalcemia which is due high levels of calcium in the cardiovascular system. Most frequently this is caused by deposition of calcium in tissue. Sometimes it is due to vasoconstriction.

In conclusion it is fair to say that both ischemic and nephrotoxic ARF cause acute tubular necrosis (ATN). However, ATN is less pronounced in nephrotoxic ARF.

Allergic interstitial nephritis can be lead to ARF Causes, mainly:

1. Antibiotics: Penicillins and Cephalosporins are most frequently implicated.
2. Nonsteroidal anti-infmlammatory drugs like acetaminophen (Tylenol) and ibuprofen are also implicated.

Common signs and Symptoms

• Febrile states (pyrexia) associated with rash is a common feature. Joint pains, called arthralgia may be seen.
• Right, left or bilateral flank pain may be exhibited by some patients. Sometimes this is associated with obstruction of the renal artery or vein. Severe glomerulonephritis may be present.
• Mild to severe headaches associated with dizziness and confusion may be seen in the early stages of ARF. In the later stages, seizure-associated with malignant hypertension will occur.
• Decreased urinary output, urine output of less then 500 mls in an adult patient. Oedema and hypertension.
• Examination of the optic disc will reveal Papilledema
• Heart failure is sometimes seen
• Malignant hypertension associated with heart failure.

Frequent Complications of ARF

Metabolic acidosis is a frequent complication of ARF. Metabolic Acidosis is defined “impaired secretion of sodium and potassium and an imbalance of chloride”. This condition then leads to other mineral and electrolyte imbalances. Several other complications often occur during the course of intrinsic ARF. These are as follows:

1. Elevated levels of serum potassium. (Hyperkalmia)
2. Elevated levels of magnesium in serum. (Hypermagnemesia).
3. Elevated levels of phosphates in serum. (Hyperphosphatemia)
4. Decreased levels of calcium in serum. (Hypocalcemia)
5. Circulatory overload. In this condition there is excess fluid in the circulatory system and the kidneys are unable to excrete that fluid.
6. Uremia will occur. High levels of nitrogenous wastes stay in the circulatory blood. Nitrogenous wastes are the by products of protein metabolism.

Diagnosing Intrinsic ARF

The usual rules apply for diagnosing this condition. First an accurate history is taken. The signs and symptoms of the disease are noted. Then blood tests, urinalysis and imaging x-rays are performed.

Blood tests: Patients with intrinsic ARF are likely to show the following:

1. High levels of serum creatinine due to renal ischemia, atheroembolism, or exposure to radiocontrast dye
2. Severe and chronic anemia (low haemoglobin / red blood count). May indicate TTP-HUS.
3. High levels of blood potassium. (Hyperkalemia),
4. High levels of phosphorous. (hyperphosphatemia) and
5. Low levels of blood calcium. (hypocalcemia) occurs mainly in rhabdomyolysis.

Urinalysis: Urinalysis will show many red and white cells in the urine. The level of sodium will generally be high. Failed filtering will result in proteinuria. Mild proteinuria suggests that renal failure is caused by injured tubules. Moderate proteinuria indicates glomerular injury. Heavy proteinuria indicates allergic interstitial nephritis.

Renal biopsy: This may be performed when laboratory test results are inconclusive or suggest more than one possible cause of intrinsic ARF.

Ultrasound: This examination is performed to rule out postrenal obstruction as the cause of the symptoms. Postrenal obstruction is obstruction in the urinary bladder or urethra.