Chronic Kidney Disease (CKD): Overview, Causes, and Management

What is CKD?

 The kidneys are known to perform the following functions:

• Urine production
• Balance minerals in the body
• Blood pressure control
• Helps in the synthesis of red blood cells (RBCs)
• Maintain bone strength.
• Maintain acid and base balance in the body.

• Chronic kidney disease (CKD), also known as chronic kidney failure, leads to the gradual and irreversible loss of all the above-mentioned kidney functions.
•  In most cases, the early signs and symptoms remain unrecognized, and only once the condition progresses to an advanced stage does the diagnosis happen.

Advanced chronic kidney failure can lead to a dangerous level of the buildup of:

• Fluid
• Electrolytes
• Wastes

Treatment mainly focuses on slowing down kidney damage. This is mostly done by controlling the cause that leads to the damage. CKD finally causes end-stage kidney failure. This can only be managed by relying on dialysis and kidney transplants.

Aetiology

Chronic kidney disease occurs due to conditions or diseases causing impairment of the kidneys, leading to damage and worsening over several months or years.

• The diseases and conditions that can ultimately lead to chronic kidney disease are the following:
  • Uncontrolled type 1 and 2 diabetes mellitus
  • Uncontrolled hypertension
  • Interstitial nephritis (Inflammation of the kidney's tubules and surrounding structures)
  • Glomerulonephritis (Inflammation of glomeruli)
  • Prolonged obstruction of the urinary tract. This can be due to the following:
    • enlarged prostate.
    • Kidney stones
    • → Certain cancers

• Polycystic kidney disease or any other hereditary kidney disease.
• Recurrent kidney infections (Pyelonephritis)
• Vesicoureteral reflux (A condition that causes the urine to go back into the kidneys)
• Renovascular disease

Also read: Understanding Addison's Disease: Causes, Symptoms, and Treatment

What are the risk factors that increase the risk of CKD?

• Cardiovascular disease
• Cigarette smoking
• Obesity
• A family history of kidney disease
• Older age
• Abnormal kidney structure
• Frequent use of certain medications that can damage the kidneys.
• Vasculitis
• Atherosclerosis
• Systemic lupus erythematosus

What are the complications of chronic kidney disease?

• Hyperkalaemia (Can affect the proper functioning of the heart)
• Hyperphosphatemia
• Metabolic acidosis
• Fluid retention, which causes:
  • Swelling of one's arms and legs
  • High blood pressure
  • Pulmonary oedema

• Increased risk of bone fractures, which is a result of the weakening of the bones due to vitamin D deficiency (osteomalacia) and osteoporosis.
• Secondary hyperparathyroidism
• Restless leg syndrome
• Anemia
• Impaired platelet function and prolonged bleeding time.
• Decreased libido.
• Hyperprolactinemia
• Hypogonadism
• CNS damage can cause:
  • Personality changes
  • Seizures

• Decreased immune response (causes increased incidence of infections)
• Complications in pregnancy (can be life-threatening to both the mother and the child)
• Pericarditis
• End-stage kidney disease

Epidemiology

Chronic kidney disease affects >800 million individuals worldwide (more than 10% of the general population worldwide). It is more common among the following groups:

• Women
• Older people
• Racial minorities
• People with diabetes mellitus
• People suffering from hypertension.

CKD hits hard among the middle and lower-middle-class populations. Over the past 2 decades, CKD has become one of the leading causes of mortality worldwide.

Explain the stages of CKD.

In the initial stage of CKD, the abnormalities would not be noticeable to a huge extent. Because initially, only a few tissues lose their function, and the remaining tissues compensate for it. This phenomenon is known as renal function adaptation. Hence, chronic kidney disease is known in the initial stages as:

• Diminished renal reserve.
• Renal insufficiency

As the renal function decreases, it interferes with the kidney's ability to maintain fluid and electrolyte homeostasis. This affects the ability of the kidney to concentrate urine and excrete excess amounts of potassium, phosphate, and acid.

The ability to effectively dilute or concentrate the urine is lost at this stage. This causes urine osmolality to be fixed at around 300 to 320 milliosmole/kg (close to plasma osmolality).

Urinary volume does not change accordingly with water intake in the advanced stage of CKD.

• The progression of CKD mainly involves:
  • The recruitment and engagement of cellular processes.
  • Biochemical pathways of cell injury that contribute to these processes.

• A lot of these processes can spread beyond their point of origin.
• This leads to the gradual loss of functional nephrons in the renal system.
• Different biochemical pathways contribute to the progression of CKD.
  • Angiotensin II induces TGF-Beta1 and the consequent elaboration of the extracellular matrix.
  • Angiotensin II also induces oxidative stress, which can upregulate TGF-Beta1 in vicinal cells and thus propagate fibrosing responses.
• Thus, these compartmental processes are outside their area of occurrence. Along with this, the versatility of injurious biochemical pathways not only underlies the pathogenesis of CKD but also holds substantial therapeutic significance. A combined multipronged therapeutic approach can interrupt these processes and pathways and thus prevent or retard the progression of CKD.

What is the glomerular function rate (GFR)?

Glomerular function rate (GFR), when the renal failure becomes advanced, is ≤ 15 mL/min/1.73 m2. 

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Symptoms and Diagnosis

Clinical Features

Depending on the severity of the condition, the signs and symptoms involve:

• Nausea
• Vomiting
• Trouble sleeping
• Muscle cramps
• Loss of appetite
• Weight loss
• Fatigue
• Weakness
• Dry and itchy skin
• Shortness of breath (If fluid builds up in the lungs)
• Hiccups
• Swelling of ankles and feet
• Increased blood pressure
• Chest pain (If fluid builds up around the lining of the heart)
• Kussmaul respiration (deep and rapid)
• Urinating more (mostly at night) than usual or less than usual
• Decreased mental sharpness/coma.
• Seizures

These signs and symptoms are mostly non-specific. These clinical manifestations may not even occur until any irreversible damage occurs to the kidney. Early diagnosis and treatment may help prevent CKD's progression into kidney failure.

Investigations

Suggested investigation in chronic kidney disease

• Initial test:  Interpretation
• Urea and creatinine: To assess stability /progress—compare to previous results
• Urinalysis and quantification of proteinuria: haematuria and proteinuria may be indicative causes. Proteinuria indicates risk of progressive CKD requiring preventive ACE inhibitor or ARB therapy
• Electrolytes: To identify hyperkalemia and acidosis
• Calcium, phosphate, parathyroid hormone and 25 (OD)D : Assessment of renal osteodystrophy
• Albumin: Low albumin—consider malnutrition, inflammation
• Full blood count (±Fe, ferritin, folate, B ) 12:  If anemic, exclude common non-renal explanations, then manage as renal anemia
• Lipids, glucose ± HbA1c : Cardiovascular risk high in CKD: treat risk factors aggressively
• Renal ultrasound: Only if there are urinary symptoms (to exclude obstruction) or progressive CKD. Small kidneys suggest chronicity. Asymmetric renal size suggests renovascular or developmental disease
• Hepatitis and HIV serology: If dialysis or transplant is planned. Hepatitis B vaccination  recommended if seronegative
• ECG:  If patient is >40 years old or hyperkalemic, or there are risk factors for cardiac disease

• Blood tests: Elevated creatinine, Elevated urea, and Anemia
• Urinalysis: A urine test can detect the presence of albumin in the urine. Kidney damage leads to the presence of albumin in the kidneys.
• Kidney scans
  • Ultrasound scans help to determine the size and shape of the kidney.
  • In rarer cases, an MRI or CT scan is taken.
  • A CT scan involves using dyes that are injurious to the kidneys. Hence, a CT scan is not 
  • considered a common diagnostic method.

• Kidney biopsy: Analysis of a kidney tissue sample helps make a more precise diagnosis. It is also considered a rather easier method of diagnosis of CKD.
• Chest X-ray: Pulmonary oedema is detected by carrying out a chest X-ray.
• GFR: The filtering rate of the kidney (quantity of waste filtered in a particular period) is detected by finding out the GFR (glomerular filtration rate).

Also read: Hypertension in Pregnancy: Types, Causes & Treatment  

Management

The treatment option adopted or recommended by the health care provider depends on the stage of CKD. The main treatment options are:

• Lifestyle changes
• Medicines (Help to control the associated problems such as high blood pressure and high cholesterol)
• Dialysis
• Kidney transplant

Lifestyle changes

• Abstain from smoking.
• Regular exercise
• Following a balanced and healthy diet
• Reduce potassium, phosphate, and protein intake.
• Ensure adequate calorie intake.
• Restrict salt intake (< 6 g per day—around 1 teaspoon)
• Maintain body weight.
• Manage alcohol intake.
• Stay clear of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs)

Medicine

• There are no particular medicines that are specifically prescribed for CKD.
• But certain medicines can help to keep many of the problems that cause CKD at bay.
• Certain other medicines can also help treat or prevent many complications that may occur as a part of CKD.
• High blood pressure medications: Maintaining normal blood pressure is of paramount importance to protect the kidneys from undergoing any damage. People with kidney disease should maintain their blood pressure below 140/90 mmHg. In the case of diabetic patients, blood pressure should be maintained below 130/80 mmHg. Angiotensin-converting enzyme (ACE) inhibitors are often the most widely used blood pressure medicine.
  • Examples of ACE inhibitors are:
    • Ramipril
    • Enalapril
    • Lisinopril

The side effects of ACE inhibitors are the following:

→ Dizziness

→ Persistent cough

→ Headaches

→ Tiredness and weakness

• Angiotensin-II receptor blocker (ARB) is used if the above side effects become severe or troublesome. 
• Medication to be taken for high albumin to creatinine (ACR) ratio or diabetes: In the case of type 2 diabetes or high albumin to creatinine ratio (ACR), dapagliflozin and medicines for high blood pressure are used. Dapagliflozin can help lower the blood sugar level and reduce the damage to your kidneys.

• Medications for anemia: Recombinant human erythropoietin
• Medications to be taken to manage high cholesterol: CKD patients are at risk of cardiovascular disease, including heart attack and stroke. Statins are prescribed to reduce the risk of developing cardiovascular disease. Examples of statins include:
  • Simvastatin
  • Atorvastatin

Side effects of statins include: Feeling sick, muscle and joint pain, constipation or diarrhea, and headaches.

Also read: Understanding Cardiac Tamponade: Causes, Symptoms, and Treatment 

What is kidney dialysis?

Kidneys will cease to function when CKD reaches an advanced stage. This affects a small proportion of people who are suffering from CKD. This happens gradually.

Indications for dialysis: AEIOU

→ A: Acid-base disorders

→ E: Electrolyte disorders (hyperkalemia mainly)

→ I: Intoxications

→ O: Fluid Overload

→ U: Uraemia

What are the types of dialysis?

Dialysis is of two types:

Haemodialysis

In this method, an external machine filters the blood diverted into it before being returned to the body. It is usually performed 3 times a week.

Peritoneal dialysis

Dialysis fluid is pumped into space inside one's stomach to draw out waste from the blood as it passes through the vessels lining the inside of the stomach. It is performed at home several times a day or overnight.

What is kidney transplantation?

A kidney transplant is a management option for people with severely damaged kidneys. It is the most effective management option for advanced kidney disease. Immunosuppressants are to be taken for the rest of one's life to stop the body from attacking the donor organ. Dialysis is performed while waiting for a kidney transplant or until a suitable donor is found. About 90% of transplants still function after 5 to 10 years post-transplantation.

Things to remember about CKD 

Supportive treatment: Supportive treatment is given if kidney transplantation cannot

be performed for certain people (for various reasons, such as those suffering from other illnesses or who are unlikely to benefit from the procedure).

The aim is to control the symptoms of kidney failure. Supportive treatment includes:

• Medical care
• Psychological care
• Practical care (for both the person and their family)

Also read: Malaria Overview: Causes, Symptoms, and Treatment 

Did You Know?

• Dog species such as Bernese Mountain dogs, miniature schnauzers, and boxers are at the highest risk of CKD among all other dog species.
• Cases in which the exact cause of CKD is unknown are called chronic kidney disease of unknown aetiology.
• CKD is the 8th largest cause of in-hospital mortality in Sri Lanka.

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