Uremia

When the kidneys are not functioning properly, dysfunction can occur in acid-base balance, fluid and electrolyte regulation, hormone production and secretion, red blood cell formation and toxin waste elimination. Thus, uremia occurs in conjunction with other signs and symptoms of kidney dysfunction:

• Failing kidneys fail to produce the hormone erythropoietin, responsible for the stimulation of red blood cell formation and anemia sets in. Other factors also contribute to the development of anemia.
• The kidney tubule cells begin to dysfunction and organic acids that are generally excreted from the body, such as lactic acid, sulphuric acid, hippuric acid, etc, begin to build up, thereby establishing renal tubular acidosis. Characteristic clinical features of acidosis include hyperventilating, lethargy, muscle weakness and anorexia.
• Similarly, phosphate and potassium are unable to be eliminated from the body and hyperkalemia develops, a condition that can get aggravated by increased dietary potassium or the use of potassium sparing diuretic medicines like spironolactone.
• Increased phosphate level, which is inversely proportional to the calcium level in the body, causes hypocalcaemia to arise. Hyperparathyroidism also develops.
• Hyperparathyroidism due to kidney failure causes bone disease or renal osteodystrophy.
• Water retention, due to declining urine filtration, can cause sodium accumulation in the body as well.
• Insulin clearance by dysfunctioning kidneys is reduced and thus, life-threatening hypoglycemia can set in if the dosage of oral hypoglycemic agent (OHA) drugs of diabetes isn’t reduced.

Uremic toxins, which build up due to the loss of the kidneys’ filtration ability, produce oxidative stress that damages the walls of blood vessels (endothelial dysfunction) that leads to abnormalities in blood clotting. Damaged blood vessel walls cause hypercoagulability and more blood clots (thrombi) are formed. Thrombi deprive tissues of oxygen and irreversible damage to organs can happen. After the clotting factors get used up, bleeding or hemorrhage can occur. The blood pressure inside vessels also rises (hypertension). This primarily impacts the heart and brain vessels and characteristic signs and symptoms of uremia arise.

(Read more: Blood clotting disorders)

Amongst other signs, symptoms and conditions of chronic kidney disease or acute kidney injury, some clinical features of uremia are:

• Nausea
• Vomiting
• Fatigue
• Appetite loss
• Weight loss
• Itching
• Muscle cramps
• Skin pigmentation
• Increased thirst
• Visual disturbances
• Changes in mental status

However, in the case of more severe and prolonged kidney dysfunction or with rapidly deteriorating status of the patient, various more devastating clinical features may arise as complications.

Causes of rising uremia toxins in blood can be segregated as those occurring due to dysfunction before the unfiltered blood reaches the kidneys (pre-renal), due to kidney disease (renal) and those caused by obstruction to the flow of toxin excretion in urine, causing them to accumulate (post-renal).

Pre-renal causes: Reduced blood volume or impairment of blood circulation reaching the kidneys to get effectively filtered can cause azotaemia or raised blood urea nitrogen. (Read more: Blood urea nitrogen test)

Another reason could be increased production of urea. Causes include:

• Hypovolaemia (reduced overall blood volume): 
  • Haemorrhage
  • Burn injuries 
  • Peritonitis
  • Overdiuresis
• Cardiac (ineffective blood circulation):
  • Congestive heart failure
  • Cardiac tamponade
  • Pulmonary embolism
  • Cardiogenic shock in myocardial infarction (heart attack)
• Reduced blood pressure:
  • Certain bacterial infections
  • Anaphylactic shock
  • Liver cirrhosis
  • Antihypertensive (blood pressure) medicines
• Increased urea production:
  • High protein diet
  • Gastrointestinal bleeding

Renal causes: End stage renal disease (ESRD), the fifth and last stage of chronic kidney disease (CKD) is the most common cause of uremia and can be caused by the following:

• Hypertension (high blood pressure)
• Diabetes mellitus (both type 1 and 2)
• Chronic use of analgesics (NSAIDs)
• Glomerulonephritis (inflammation of glomeruli)
• Interstitial nephritis
• Chronic pyelonephritis (pus-filled infection of kidney)
• Kidney stones
• Systemic lupus erythematosus (SLE)
• Polycystic kidney disease

Post-renal causes: Obstruction to the outflow of filtered urine causes a buildup of uremic toxins in the blood thus producing azotaemia. Potential causes can be blockage of ureters or urethra by:

• Stones (kidney or bladder)
• Tumours
• Clots
• Papillary necrosis
• Benign prostate hypertrophy (BPH)

While pre-renal and post-renal causes of azotaemia are generally reversible and do not often lead to uremia, chronic kidney disease commonly precipitates uremia in its final stages.

Conditions that may increase the risk of kidney disease include:

• A family history of kidney disease
• Diabetes
• High blood pressure
• Heart disease
• Prolonged medical treatment with nephrotoxic (causing damage to the kidney) drugs like NSAIDs
• Congenital disorders of the urinary tract like:
  • Polycystic kidney disease
  • Vesicoureteric reflux

History: The doctor begins by taking a thorough medical history of the patient. A keen emphasis is paid on a history of, and complaints suggestive of, lifestyle diseases such as hypertension and diabetes, prolonged use of analgesics (NSAIDs) or other kidney damaging drugs, a family history of kidney problems and any preexisting kidney problems.

Examination: Following a medical history, a comprehensive physical examination of the patient is conducted. Owing to the wide-ranging presentation and causes of kidney disease, all systems are evaluated thoroughly. During a general examination, the blood pressure of the patient is checked and can help diagnose unrecognised hypertension. Many signs of kidney disease can even be appreciated on a simple visual inspection, such as pigmentation of skin in long-standing cases. Many neurological signs are elicited due to uremic encephalopathy such as asterixis (loss of muscle control in certain parts of the body giving rise to involuntary shock-like jerky movements especially when hands are extended and wrists are bent towards the palms) and myoclonus (quick involuntary jerky muscle spasms). However, these signs are not exclusive to kidney disease. Laboratory investigations and radiological imaging are necessary to diagnose uremia, and its cause, accurately.

Investigations that may be required to diagnose uremia include the following:

• Blood tests:
  • Complete blood count: Anemia (reduced haemoglobin) and signs of infection (raised white blood cell counts) can be detected. Platelet count may be reduced.
  • Coagulation profile: Due to uremic toxin-induced injury, a hypercoagulable state may exist. Conversely, clotting factors may subsequently get used up.
  • Blood glucose levels: Uncontrolled diabetes can cause chronic kidney disease.
  • Kidney function tests: It helps estimate glomerular filtration rate, and stage kidney disease, by measuring creatinine levels. Rising urea and creatinine levels can be detected. Electrolyte imbalance can be assessed.
  • Immunological tests: Systemic lupus erythematosus (SLE) or glomerulonephritis antibodies can be detected.
• Urine tests:
  • Urine output: Kidney failure results in declining glomerular filtration rate and large volumes of dilute urine are passed in a day.
  • Urine microscopy: Cells such as red blood cells and pus cells can indicate kidney infection or glomerulonephritis. Tumour cells can also be found. Crystals of the components of various types of kidney stones can be visualised.
  • Urine albumin: It is used to stage chronic kidney disease.
  • Urine electrolytes: Electrolyte imbalance caused by kidney dysfunction can be diagnosed.
  • Urine ketone and glucose: Uncontrolled diabetes mellitus causes glucose and ketone bodies to appear in the urine.
• Radiological imaging:
  • X-ray KUB (kidney, ureters, bladder): Congenital diseases like polycystic kidney disease can be diagnosed. Kidney tumours may be visualised as well.
  • Abdominal ultrasound: Kidneys and other structures of the urinary tract are assessed.
  • CT scan/ MRI: CT scans and MRIs are other modalities that can be used for the same purpose.
  • Brain imaging: MRI is especially useful to distinguish uremic encephalopathy from other organic brain diseases.
  • Chest X-ray: Signs of pulmonary edema can be viewed.
• Other investigations: 
  • Electrocardiograph (ECG): Suspicion of uremic pericarditis may warrant an ECG in order to differentiate it from heart attack.
  • Electroencephalogram (EEG): Brain waves are assessed to rule out other causes of seizures and other symptomatology.
  • Kidney biopsy: At times, when the cause of kidney disease can not be discerned, a biopsy might be considered.

Although the aim remains to adequately treat kidney disease (and its underlying cause) to prevent end-stage renal disease, if uremia has set in, irreparable damage to kidneys has already been done. Thus, the principal treatment of uremia is to clear the body of toxins by renal replacement therapy:

• Regular dialysis: Extra toxins, electrolytes and fluid is removed from the patient’s blood artificially. Two types of dialysis are carried out:
  • Haemodialysis: An artificial arteriovenous fistula is made in the patient’s arm. An “artificial kidney” or dialysis machine is hooked onto it and unfiltered blood is drawn into it. The blood gets filtered and is pumped back into the patient’s body. Two to 3 sittings per week, lasting 4 to 5 hours, are the norm.
  • Peritoneal dialysis: A catheter (small tube) is inserted into the patient’s abdomen and a dialysis fluid is filled. The toxins, electrolytes and extra fluid are removed through it in a cyclical manner.
• Kidney replacement: If a suitable (HLA-matched) donor is available and willing to donate one of their kidneys, the patient may undergo a kidney replacement surgery, followed by rigorous immune system suppression therapy to prevent rejection of the new organ.

Some complications that can arise from uremia are the following:

• Loss of libido: Impotence in men and amenorrhea (absence of menstruation) in women can arise due to hormonal imbalance caused by prolonged uremic toxin accumulation in the body.
• Peripheral neuropathy: Paraesthesias (or lack of sense of touch) can develop due to long-standing accumulation of uremic toxins and damage to the nerves.
• Uremic encephalopathy: Uremic toxins accumulate in the brain and act as neurotoxins. They cause damage to blood vessels in the brain and also dysregulation of neurotransmitter chemicals. Uremic encephalopathy is progressive if left untreated and needs to be differentiated from other causes with similar symptomatology. Some features include: mild sensory clouding, delirium, myoclonus, asterixis, seizures or coma.
• Uremic lung: Due to a variety of reasons (most prominent being fluid overload in the body and the lungs and injury and inflammation of the lung blood vessel walls by the uremic toxins) pulmonary edema (accumulation of fluid in the lung) sets in. The patient usually becomes breathless and if untreated, can develop congestive heart failure.
• Uremic pericarditis: Due to fluid overload, electrolyte imbalance and uremic toxin accumulation, the pericardium (covering layer of the heart) of the heart gets inflamed. Patients experience a sharp searing chest pain (pleuritic chest pain), along with shortness of breath. This pain has to be differentiated from the pain of myocardial infarction or heart attack.

If one is suffering from advanced kidney disease, the best way to prevent uremia is by:

• Regular dialysis: Dialysis sessions should not be missed as devastating complications can arise.
• Healthy diet: The doctor might advise patients, on a case by case basis, to avoid excessive potassium, salt or phosphates in food. If such a plan is presented to the patient, it should be followed.
• Controlling diabetes mellitus: It can prevent progression to end-stage renal disease (ESRD).
• Managing hypertension: ESRD can be avoided.
• Quitting smoking

Uremia is progressive and can be life-threatening. It is important to prevent it. If it sets in, medical treatment should be sought immediately.

(Read more: Chronic Kidney Disease Diet Plan)