Chronic Kidney Disease (CKD):

• A gradual decline in kidney function over months to years.
• Progressive loss of nephrons.
• Eventually leads to end-stage renal failure, requiring dialysis or transplantation.
• Usually associated with long-term hypertension, diabetes mellitus, or chronic glomerulonephritis.

Causes of Chronic Kidney Damage:

• Secondary to uncontrolled hypertension: Long-standing high BP damages blood vessels, causing narrowing.
• Secondary to diabetes mellitus: High blood sugar damages blood vessels, promoting both atherosclerosis and fibrosis.
• Atherosclerosis:  Narrowing of renal blood vessels leads to ischemia
• Systemic Lupus Erythematosus (SLE): An autoimmune disease in which autoantibody-antigen complex deposition causes vasculitis including glomerular inflammation.
• Polycystic kidney disease: Inherited genetic disease causing progressive renal cyst formation and scarring.
• Long-term exposure to nephrotoxic drugs: NSAIDs, certain antibiotics (sulfa drugs), or toxins damages nephrons.

Progression & Damage:

• Damage affects both kidneys for irreversible renal failure.
• The process involves glomerular and nephron destruction, reducing filtration capacity.

Chronic Kidney Disease (CKD) – Stages, Symptoms, and Diagnostic Approach:

*Note: 5 Stages of CKD have replaced the older 3 stage system (stage 1=risk, stage 2=injury, stage 3=failure)

~Stage 1: Decreased Renal Reserve:

• • Chronic Kidney Disease Definition:  GFR is reduced for at least 3 months, but kidney function appears normal clinically.
  • Renal Insufficiency: defined as kidneys are not functioning at full capacity either due to acute or chronic kidney injury
  • GFR: as measured by comparing serum creatinine to urine creatinine levels
  • Signs:  Usually asymptomatic. Kidney damage can be asymptomatic until significant amount of renal function is lost
  • Blood Test findings:  Slight rise in serum creatinine; serum urea remains normal.

• If Urinalysis is performed, signs may be present:
  • Glomeruli damage: can cause proteinuria, hemoglobinuria, and possibly myoglobinuria (if rhabdomyolysis is a factor)
  • Proteinuria and Albuminuria: Due to damaged glomeruli (amount of albumin in urine, reflects severity of glomerular damage). Protein in filtrate can cause urinary casts.
  • Nephron tubule damage: can cause urinary casts

• Pathology:  Some nephrons are damaged; remaining nephrons hypertrophy to compensate, increasing workload 3-5 times.
  • Vascular damage: Hypertension worsens renal damage.

~Stage 2-4:  Development of Renal Insufficiency

• GFR:About 20-75% of normal.
• Signs:
  • Nephrons hypertrophy, and increase their filtering rates by 3-5 times, meaning that serious symptoms may not start occurring until ~25% of functioning nephrons are left.
    • Polyuria:Dilute urine due to impaired concentration.
    • Electrolyte imbalances:Hyperkalemia, acidosis.
    • Mild swelling of hands and feet (edema)
    • Serum waste buildup:Elevated serum creatinine and urea (rise in nitrogenous wastes = azotemia).
    • Fatigue, malaise, anorexia (loss of appetite):Due to toxin buildup and metabolic disturbances.
    • Bone pain:Due to osteodystrophy caused by calcium and vitamin D imbalance.
    • Growing damage, loss of nephrons, increasing scarring and fibrosis.
    • Anemia
      • Due to decreased erythropoietin (EPO)secretion by kidney cells.
      • Results in decreased red blood cell countand fatigue.
    • Bone marrow depression (low RBC, WBC, & platelets) and impaired cell function
      • Caused by increased wastes and altered blood chemistry
      • Leads to easy bruising; epistaxis (nose bleeds), anemia; fatigue
    • Uremia:Dry, itchy skin, hyperpigmentation (possibly due to reduced cutaneous blood and dehydration of cells), easy bruising, bleeding.  Possibly uremic frost on skin, brittle fingernails
    • Neurological symptoms:Lethargy, memory issues, seizures, tremors (uremic encephalopathy).
    • Peripheral neuropathy (abnormal sensations in legs); restless leg
    • Cardiac arrhythmias:Due to electrolyte imbalances like hyperkalemia, hypocalcaemia.
    • Gastrointestinal issues:Nausea, ulcers, bleeding.
    • Bone abnormalities:Osteodystrophy from calcium and vitamin D deficiency, due to failure of kidney cells to activate vitamin D (which is converted to calcitriol, which is required for optimal absorption of calcium by intestines, which may also be negatively impacted due to GI disturbances).
    • Impotence in men, menstrual irregularities in women (possibly heavy menstruation)
    • Infections:Increased susceptibility from immune suppression (low WBCs).
    • Blood pressure:  Can be elevated due to fluid overload or pre-existing hypertension.

~Stage 5: End-stage renal failure

• • • GFR:  Less than 15 mL/min (nephron function severely compromised).
    • Signs: All signs and symptoms depicted in stages 2-4 Renal Insufficiency continue, and worsen, becoming more severe.
      • 5As: Anuria, Anemia, Azotemia, Anorexia, Acidosis
      • Uremia:  Nitrogen waste buildup causes systemic toxicity that affects all tissues, causing organ dysfunction.
      • Oliguria or anuria:  Little or no urine output. No urine production (anuria) indicates severe damage.
      • Multisystem effects:  Cardiac dysrhythmias, neurological deficits, muscle weakness, skin alterations (uremic frost, hyperpigmentation).
    • Consequences:
      • Organ failure if not treated.
      • Requires dialysis or transplant for survival.

Diagnostic Tests:

• Blood tests:  Urea, creatinine, electrolytes, acid-base balance.
• Urine output:  Monitored for oliguria, anuria, or polyuria.
• Urinalysis: Proteinuria, Urinary Casts
• Imaging:  Ultrasound or Doppler to assess kidney size, structure, and vascular flow.
• Biopsy:  To determine specific areas of damage or inflammation.

Management:

• Dialysis:  To remove wastes, excess fluid, and correct electrolyte imbalances.
• Medications:  Therapies aim to slow progression of the disease
  • Erythropoiesis-stimulating agents for anemia.
  • Manage primary cause (e.g., medically control hypertension, diabetes mellitus, maintain heart health)
  • Phosphate binders, vitamin D for bone disease.

Diet:

• • Fluid, salt, and protein restriction to reduce kidney workload.
  • Limit water and salt intake to reduce blood volume.
  • Minimize protein intake to decrease nitrogenous waste production.
• Counteract acidosis: Administer bicarbonate ions to buffer excess acid.
  • Manage electrolytes carefully to prevent imbalances.
• Goals: Slow disease progression, prevent further damage, and manage symptoms.

Signs of Recovery:

• Early signs: Increased urine output(diuretic stage).
• Regain ability to filter nitrogenous wastes and maintain water-salt and pH of blood

Signs of Advance Failure:

• Poor prognosis if untreated:
  • Progression to failure stages.
  • Accumulation of toxins in blood.
  • Prolonged kidney failure leads to death.

Prevention:

• Control underlying conditions such as hypertension and diabetes.
• Regular monitoring and early intervention in high-risk patients.

Curative Treatment:  

• Kidney transplant:
  • though addressing underlying causes of kidney disease still need to be treated
  • For end-stage renal disease, improves quality of life and survival.
  • 50% kidney function can sustain life.  A person can survive with 1 kidney.

Summary:

Chronic kidney injury progresses slowly due to vascular disease, hypertension, or diabetes mellitus, leading to irreversible damage if untreated. Early signs include changes in urine volume, azotemia, and anemia. When kidney function deteriorates beyond recovery, dialysis or transplantation becomes necessary. Managing the primary cause and early intervention are crucial to prevent death.

CKD progresses through stages marked by decreasing GFR, with early stages often asymptomatic. Advanced renal failure leads to systemic toxicity (uremia), multisystem organ failure, and requires aggressive management including dialysis or transplant to sustain life. Chronic kidney disease develops insidiously, resulting in irreversible renal failure if untreated.