Chronic Kidney Disease (CKD) – Symptoms and Treatment

Chronic Kidney Disease (CKD) is a collection of symptoms that develop as a result of progressive kidney disease lasting more than three months. These symptoms arise due to the gradual and irreversible death of nephrons (the structural units of the kidneys). Previously referred to as chronic renal failure, this term now specifically denotes the severe stage of the disease.

The symptoms of CKD depend on the extent of kidney damage. Initially, there might be no symptoms, and the patient may only be concerned with signs of the underlying condition, such as high blood pressure. Later, patients may notice increased nighttime urination, high blood pressure, or a lack of response to typical blood pressure medications. Symptoms of end-stage CKD include severe weakness, ammonia-like breath odor, and dry, itchy skin.

Prevalence of CKD

Approximately 13% of the global population suffers from CKD. This percentage is consistent in both high-income and developing countries. Each year, the number of patients increases by 10%. CKD is nearly as common as hypertension, diabetes, metabolic syndrome, and obesity. One in ten patients shows signs of kidney damage.

Risk Factors for CKD

The risk factors for CKD can be classified into modifiable and non-modifiable factors. Non-modifiable factors include advanced age, genetic predisposition, a low number of nephrons at birth, previous acute kidney injuries, and racial or ethnic factors. Modifiable factors include hypertension, diabetes, smoking, the toxic effects of medications, chronic inflammation or systemic infections, urinary tract obstructions, pregnancy, and high protein intake.

Symptoms of CKD

In the early stages, CKD can only be diagnosed by the presence of protein in the urine, typically albumin. This is often accompanied by symptoms of the underlying condition, such as hypertension and elevated blood sugar levels. As the disease progresses, urine output increases (polyuria), reaching 2-3 liters daily. Nocturnal urination (nocturia) also increases, with patients urinating two or more times at night, often producing more urine at night than during the day. Polyuria and nocturia, especially when accompanied by anemia, should raise suspicion of CKD. The disease may also present with facial, hand, or foot edema, persistent thirst, general weakness, loss of appetite, and elevated blood pressure. As the disease progresses, patients lose weight, experience increased weakness, and their capacity for work diminishes. Hypertension becomes uncontrolled, meaning medications are no longer effective.

In the late stages of CKD, urine output decreases significantly until it ceases altogether in the final stage. Patients become lethargic and slow, suffering from severe weakness, nausea, dry mouth, a bad taste in the mouth, aversion to food (especially meat), yellowish, pale, and greyish skin, itchy skin, coldness, and cramps in the leg muscles. Blood pressure may drop, and patients may feel pain in the joints, bones, and spine, as well as a burning or tingling sensation in the legs.

All symptoms of CKD are non-specific except for changes in urine output. These symptoms appear in diseases that lead to CKD development, such as hypertension or diabetes. Kidney damage might be suspected if there is pain and discomfort in the lower back and changes in urine color to red, brown, foamy, or urine that contains sediment and clumps.

Development and Progression of Chronic Kidney Disease (CKD)

Structure of the Nephron

Nephrons consist of small filters called glomeruli that filter fluids. Proteins and cellular elements remain in the blood, while the filtered primary urine is discharged through small tubes.

Mechanism of Chronic Kidney Disease

Despite the diverse causes of CKD, the morphological changes in the kidneys are similar. In kidney diseases, the number of functional nephrons decreases, leading to an increase and acceleration in the volume of blood filtered per unit time. Additionally, the pressure in the remaining glomeruli increases, resulting in increased capillary permeability and elevated levels of albumin in the urine. This protein can deposit in the spaces between the glomerular capillaries, causing these spaces to expand and accumulate a hyaline-like cartilage tissue. Eventually, nephrons are replaced by connective tissue, and the kidneys shrink, perpetuating a vicious cycle.

Decline in Healthy Nephron Count

The reduction in the number of healthy nephrons impairs the kidneys’ ability to eliminate the end products of nitrogen metabolism, such as creatinine, urea, uric acid, and ammonia, leading to uremia. Symptoms of uremia include weakness, apathy, loss of appetite, nausea, vomiting, itchy skin, and aversion to food, especially meat.

Uremic Toxins

Uremic toxins also include parathyroid hormone. Its excessive production initially lowers calcium levels and raises phosphorus levels to correct uremia-related imbalances. Later, this hormone becomes a toxic substance, exacerbating the severity of uremia.

Effects of Elevated Parathyroid Hormone

Over time, elevated parathyroid hormone levels lead to renal osteodystrophy, where:

Bone tissue becomes porous and brittle, causing bone deformities and fractures.
Triglyceride levels increase.
Anemia worsens.
Calcium salts accumulate in tissues, including the heart muscle and heart valves.

Changes in Urine Production

The remaining healthy nephrons must filter a larger amount of material per minute, leading to increased urine volume (polyuria) and increased nighttime urination (nocturia).

Decrease in Glomerular Filtration Rate

Even with a significant decrease in the glomerular filtration rate, the kidneys can continue producing and excreting urine (diuresis) by adjusting urine concentration. The relative density of urine drops to the density of protein-free plasma filtrate (1010-1012 g/L). Consequently, the end products of electrolytic and electrochemical exchange accumulate in the blood, exacerbating uremic symptoms.

Difficulty in Sodium Filtration

Normally, the kidneys can filter the amount of sodium consumed by a person. As CKD progresses, sodium filtration becomes more challenging, and the kidneys’ ability to eliminate it through urine diminishes. Sometimes, the kidneys lose the ability to reabsorb sodium, leading to a decrease in its concentration in the urine. This results in salt depletion, causing a sharp drop in blood pressure, severe weakness, and rapid progression of CKD.

Hyperkalemia

In the late stages of CKD, due to a significant reduction in urine production and glomerular filtration rate, blood potassium levels rise to 5 mmol/L, a condition known as hyperkalemia. In some cases, such as diabetic nephropathy and tubulointerstitial kidney diseases, hyperkalemia appears earlier. Infections, injuries, hyperthermia, and the use of potassium-sparing diuretics (spironolactone, triamterene, amiloride) can exacerbate this condition.

Impact of Hyperkalemia

Hyperkalemia impairs the transmission of electrical impulses through neuromuscular cells, which can lead to paralysis and bradycardia, potentially resulting in complete heart arrest.

Classification and Stages of Chronic Kidney Disease (CKD)

International Classification of Diseases

In the International Classification of Diseases (ICD-10), Chronic Kidney Disease (CKD) is coded as N18. This disease is designated as a separate nosological entity because the mechanism of kidney damage, factors in disease progression, and preventive measures are similar across different diseases.

CKD Classification Based on Glomerular Filtration Rate (GFR)

CKD is classified based on the Glomerular Filtration Rate (GFR), which measures the volume of fluid filtered from the glomerular capillaries into the capsule per unit time.

Stages of CKD according to GFR:

Stage 1: Normal or high GFR (≥ 90 mL/min).
Stage 2: Slight decrease in GFR (60–89 mL/min).
Stage 3a: Moderate decrease in GFR (45–59 mL/min).
Stage 3b: Significant decrease in GFR (30–44 mL/min).
Stage 4: Severe decrease in GFR (15–29 mL/min).
Stage 5: End-stage renal disease (GFR < 15 mL/min).

Signs of kidney damage appear in all stages, starting from stage 1.

Acute Kidney Disease

In addition to the chronic form, there is also Acute Kidney Disease (formerly known as acute renal failure). In the acute form, symptoms develop rapidly, but this condition is often reversible within three months. If recovery does not occur within this period, the kidneys may fail permanently.

Stages of CKD According to Clinical Presentation

Stage 1 (Initial or Latent Stage): Increased urine production, high blood pressure in half of the patients, and mild anemia may appear. GFR ranges from 40-80 mL/min. This stage corresponds roughly to stages 2 and 3a of the GFR classification.
Stage 2 (Conservative Stage): Patients continue to produce a large amount of urine, blood pressure remains high, and nocturnal urination increases. Anemia progresses to a moderate degree, and blood creatinine levels rise to 145-700 µmol/L. GFR ranges from 10-40 mL/min. This stage corresponds roughly to stages 3b and 4 of CKD by GFR.
Stage 3 (Terminal Stage): High urine production transitions to a significant reduction. Severe anemia appears, and levels of phosphate, potassium, sodium, and magnesium increase. Blood creatinine exceeds 700-800 µmol/L. GFR is less than 10 mL/min. This stage corresponds to stage 5 of the GFR classification.

Complications of CKD

CKD leads to numerous complications affecting various systems, including the cardiovascular system, vitamin D deficiency, bone disorders, and many others.

Cardiovascular Complications:

Sodium Retention: Occurs in 80% of patients, leading to high blood pressure, which may persist for long periods, is difficult to treat, and causes damage to the retina, brain, kidneys, and heart. High blood pressure can also lead to strokes, encephalopathy, seizures, and retinopathy. Additionally, high blood pressure, combined with anemia and other pathological factors, increases the workload on the left side of the heart, leading to left ventricular hypertrophy.
Proteinuria and Dyslipidemia: Increased protein excretion in the urine, altered insulin metabolism, and elevated parathyroid hormone levels lead to higher levels of atherogenic lipids such as triglycerides and apolipoproteins B, resulting in coronary atherosclerosis, reduced heart blood supply, and heart attacks.
Pericarditis: In advanced stages, fibrous or exudative pericarditis may develop, leading to pressure on the heart muscle and increased risk of chronic heart failure.

Vitamin D Deficiency Complications:

Patients experience reduced formation of hormonally active vitamin D (calcitriol) in kidney tissues, exacerbating its deficiency as kidney function declines. This deficiency, along with high levels of calcium and phosphate, leads to secondary hyperparathyroidism, affecting 30% of dialysis patients.

Bone System Complications:

Elevated parathyroid hormone negatively impacts many organs, causing calcium accumulation in heart valves, the heart’s electrical system, and blood vessels, leading to cardiomyopathy, aggravated atherosclerosis, hypertension, and heart failure.
In children, hyperparathyroidism can cause renal rickets, similar to traditional rickets. This results in bone erosion and deterioration, replacement of bone marrow with connective tissue, and osteosclerosis, increasing the risk of fractures, especially in the ribs and femoral neck.

Other Complications:

Anemia: Affects 4-8% of patients in early stages, increasing to 50-80% as the disease progresses.
Hypoalbuminemia: Caused by albumin loss in urine, poor protein intake, poor protein absorption in the gastrointestinal tract, and increased protein breakdown, leading to protein-energy malnutrition.
Metabolic Acidosis: Increased blood acidity due to protein breakdown, leading to tachycardia, arrhythmias, ventricular fibrillation, and reduced heart contraction efficiency.
End-Stage Disease: The kidneys cease urine production, and uremic toxins like urea and creatinine accumulate in the blood, causing nausea, vomiting, itchy skin, bleeding, and weight loss due to persistent vomiting.

These complications are serious and require ongoing medical management to prevent exacerbation and control symptoms.

Diagnosis of Chronic Kidney Disease (CKD)

Medical History Collection

When diagnosing CKD, a general practitioner or nephrologist pays attention to the following symptoms:

Frequent urination, especially at night (nocturia).
Changes in urine color or the presence of impurities (blood, protein).
Swelling and pain in the flank area.

The doctor will clarify:

When these symptoms started and how long they have lasted.
Whether the patient has any diseases that are risk factors for CKD, such as diabetes or hypertension.
The medications the patient is taking.

Blood Tests

To diagnose CKD, and in the presence of risk factors even without symptoms, levels of creatinine and the glomerular filtration rate (GFR) are evaluated through blood chemistry analysis. The sample is taken on an empty stomach (fasting for 8 hours before the sample).

Other blood parameters studied include:

Electrolyte balance: levels of potassium (low in early stages, high in later stages) and sodium.
Hemoglobin and creatinine levels: normocytic normochromic anemia is often present.

Urine Tests

If CKD is suspected, protein, albumin, and creatinine levels in daily or morning urine are monitored.

Key urine tests include:

General urinalysis with microscopic sediment examination.
Urine analysis for microalbuminuria.
Determination of protein in daily urine.

Special attention is given to the relative density of urine, which decreases in CKD. To determine the daily urine output, its relative density, and analyze the dynamics of these readings throughout the day, urine is analyzed according to the Zimnitsky method.

Medical Imaging

X-ray and Ultrasound of the Kidneys:

Assess kidney size and density.
In late stages, kidneys shrink and become denser.
Normal kidney sizes in progressive CKD may indicate an exacerbation of the disease, requiring treatment to improve kidney function.
Ultrasound can reveal specific pathological changes (tumor, abscess, kidney stone, tuberculosis).

Kidney Biopsy

A kidney biopsy is performed to determine the causes and severity of kidney damage and to choose the best treatment. Indications for a kidney biopsy include the presence of protein and blood in the urine in two or more tests over three months.

Differentiating Acute Kidney Failure from Chronic Kidney Disease

Acute Kidney Failure:

Develops quickly: Symptoms arise rapidly over a short period, often within days or even hours.
Specific causes: Usually linked to acute conditions such as infections, injuries, blood flow disorders to the kidneys, poisoning, or certain medications.
Treatment targets the underlying cause: Kidney function may stabilize once the primary condition is resolved.

Chronic Kidney Disease:

Progressive development: Symptoms develop slowly over months or years, often unnoticed in early stages.
Associated with long-term conditions: Causes include chronic diseases like diabetes, hypertension, atherosclerosis, and prolonged medication use.
Deteriorates over time: Early stages may be manageable, but kidney function deteriorates over time, leading to severe complications.

Common Signs in Both Conditions:

Increased creatinine levels: Creatinine, a waste product from muscle metabolism, is normally filtered by the kidneys. In kidney failure, blood creatinine levels rise.
Decreased GFR: The GFR measures how effectively the kidneys filter blood. It decreases in both acute and chronic kidney failure, although the rate and degree of decline may vary.

Understanding these differences helps doctors choose the appropriate treatment and manage the patient’s condition effectively.

Treatment of Chronic Kidney Disease (CKD)

Managing the Underlying Condition:

The treatment of CKD primarily focuses on managing the underlying condition that caused the disease, such as hypertension or diabetes.

Medications:

A variety of medications are used to address different biological processes involved in the deterioration of kidney function.
The comprehensive treatment aims to slow down the progression of end-stage renal failure and improve the patient’s quality of life.

Dietary Recommendations for CKD Patients

Protein Intake:

Patients are advised to reduce protein intake to lessen the strain on the kidneys, consuming appropriate amounts of protein based on medical advice.
In severe stages of CKD, protein intake should be limited to 0.25-0.3 g/kg per day.
High-protein foods like meat, fish, cheese, dairy products, nuts, and legumes should be limited, while low-protein foods such as vegetables, fruits, rice, honey, butter, and cooking oils are recommended.

Potassium and Phosphate:

Avoid foods high in potassium and phosphate to reduce their accumulation in the body, lowering the risk of CKD complications.

Salt Intake:

For patients with hypertension or signs of sodium retention, salt intake should be reduced to 5 grams per day.
Spices, pickles, smoked meats, and sausages should be excluded. Fatty, fried foods, and refined sugar desserts should be minimized.

Hydration:

Patients should increase their water intake appropriately to maintain fluid balance. Water can be consumed without significant restriction but should not exceed daily urinary output by more than 500 ml.

Managing Hypertension in CKD Patients

Blood Pressure Goals:

The optimal arterial pressure for CKD patients is less than 135-140/80-85 mmHg.
If proteinuria exceeds 1 gram/day, the target pressure is below 130/80 mmHg.

Long-term Hypertension Management:

Long-term, continuous treatment combining drugs from different groups, including diuretics and medications that inhibit the renin-angiotensin-aldosterone system, is essential.

Diuretics:

Diuretics like furosemide and ethacrynic acid are used to stimulate urine excretion and reduce kidney pressure.
In early CKD stages, thiazide diuretics such as hydrochlorothiazide and potassium-sparing diuretics like spironolactone and verospiron are utilized.
In advanced CKD stages, potassium-sparing diuretics are recommended for at least three months, reducing risks of heart failure, stroke, and other cardiovascular events.
Potassium levels should be closely monitored when using potassium-sparing diuretics.

Inhibiting the Renin-Angiotensin-Aldosterone System:

Beta-blockers, ACE inhibitors, AT1 receptor blockers, and calcium channel blockers are increasingly used for renal hypertension and improve glomerular filtration in some cases.

Other Pharmacological Treatments for CKD

Phosphate and Calcium Balance:

Reducing dietary phosphate intake, taking phosphate binders (e.g., calcium carbonate, aluminum hydroxide), and activated Vitamin D (e.g., calcitriol, paricalcitol) are essential.

Correcting Metabolic Acidosis:

Daily injections of sodium bicarbonate or calcium carbonate to correct acidosis.

Anemia Management:

For hemoglobin levels below 90-100 g/L, erythropoiesis-stimulating agents (e.g., epoetin beta, epoetin alpha) and iron supplements are recommended.

Carbohydrate and Lipid Metabolism:

Medications to lower blood sugar (e.g., metformin, sulfonylurea derivatives) are used, and insulin may be added if glucose control is inadequate.
Statins or fibrates are prescribed for high blood lipid levels.

Treatment of End-Stage Renal Disease

Hemodialysis:

Blood is passed through a selective permeable membrane to remove uremic toxins and excess water, sodium, and potassium.
Hemodialysis and peritoneal dialysis are available for children, with peritoneal dialysis being preferable due to ease of tolerance, ability to perform at home, and fewer life-threatening complications.

Peritoneal Dialysis:

Suitable for infants and children who cannot form adequate blood flow access.
Contraindicated in cases of catheter infections, tumors, abdominal swelling, peritonitis, or non-closure of the abdominal cavity (e.g., ileostomy, drainage).

By following these guidelines, CKD patients can manage their condition more effectively, improving their quality of life and potentially slowing the progression of the disease.

Prognosis and Prevention in Chronic Kidney Disease (CKD)

Prognosis:

Rate of Progression: Chronic kidney disease can progress at varying rates. In some cases, it can advance to a severe stage (end-stage renal disease) suddenly and even without treatment.
Influencing Factors: Infections, dehydration (such as from diarrhea or vomiting), or injuries can lead to rapid deterioration and potentially death within a few days.
Gender Differences: CKD tends to progress more rapidly in men, though the reasons for this are not fully understood.
Life Expectancy: For patients aged 44, the expected life span is between 7.1–11.5 years; for those aged 60–64, it ranges from 2.7–3.9 years. Prognosis largely depends on the underlying disease, its progression, the stage of kidney failure, and the treatment provided.
Primary Causes of Death: Patients typically die not from kidney-related causes but from other diseases such as cardiovascular complications (heart attacks, strokes, chronic heart failure), diabetes, and hypertension. Cardiovascular diseases are the most common cause of death in CKD patients, accounting for 40-60% of fatalities.

Prevention:

Risk Factor Management: Preventing CKD involves mitigating or eliminating risk factors. This includes quitting smoking, losing excess weight, controlling high blood glucose levels, and treating hypertension.
Treatment of Underlying Conditions: Managing kidney diseases such as nephritis and glomerulonephritis, surgically addressing urinary tract obstructions and renal artery stenosis in a timely manner, and properly treating conditions like tonsillitis, pharyngitis, bronchitis, gingivitis, and skin infections can slow CKD progression.
Specialist Monitoring: For CKD resulting from other conditions like diabetes or hypertension, patients should be monitored by an endocrinologist or cardiologist in conjunction with a nephrologist. The frequency of check-ups depends on the CKD stage and the level of proteinuria. Patients in stage I should see a doctor once a year, while those in stages IV-V should have visits at least every six weeks. For timely initiation of renal replacement therapy, patients in stages IV-V should be regularly monitored by a nephrologist at a dialysis center.

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