Chronic Kidney Disease Overview

Chronic Kidney Disease (CKD)

• Defined as progressive and irreversible loss of kidney function
• Characterized by glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m² for three or more months
• Affects every body system if left untreated

Most Likely Causes

• Diabetes Mellitus (Diabetic Nephropathy): Chronic hyperglycemia damages glomerular capillaries, leading to inflammation, fibrosis, and nephron loss
• Hypertension (Hypertensive Nephropathy): High blood pressure damages nephron's filtering capacity
• Glomerulonephritis: Inflammation of the glomeruli damages the filtration system
• Polycystic Kidney Disease (PKD): Genetic disorder characterized by cysts that replace normal kidney tissue
• Autoimmune Diseases: Conditions like Systemic Lupus Erythematosus (SLE) can cause glomerular injury

Pathophysiology

• Progressive nephron loss and adaptations of surviving nephrons
• Loss of Functional Nephrons: Injury (e.g., from hypertension, diabetes) leads to loss of nephrons; remaining nephrons compensate by increasing filtration (glomerular hyperfiltration)
• Hyperfiltration Injury: Increased glomerular pressure damages endothelial cells, leading to podocyte detachment and thickening of the glomerular basement membrane (GBM). This leads to proteinuria (protein in the urine), contributing to tubulointerstitial inflammation and fibrosis
• Tubulointerstitial Inflammation: Protein filtration activates tubular cells, leading to production of inflammatory cytokines, promoting fibrosis, angiotensin II upregulation, and increased production of reactive oxygen species (ROS), further damaging nephrons
• Fibrosis and Scarring: Chronic injury triggers myofibroblast production, causing extracellular matrix protein (collagen) deposition and scarring, replacing normal kidney tissue

Reduced Glomerular Filtration Rate (GFR)

• Fibrosis causes GFR decline
• GFR below 60 mL/min/1.73 m² indicates CKD diagnosis
• GFR less than 15 mL/min/1.73 m² indicates end-stage renal disease (ESRD), requiring dialysis or transplant

Disease Transmission

• CKD is not transmissible
• Results from chronic disease processes (diabetes, hypertension, autoimmune diseases) or genetic mutations (like polycystic kidney disease)
• No transmission from person to person (unless genetic predisposition)

Risk Factors

• Modifiable: Diabetes, hypertension, obesity, smoking, NSAID use
• Non-Modifiable: Age, family history, genetics (PKD), ethnicity, gender

Clinical Manifestations

• Asymptomatic early stages
• CKD symptoms appear as kidney function declines:
  • Uremia (build-up of urea in blood)
  • Electrolyte imbalances (hyperkalemia, metabolic acidosis)
  • Fluid overload
  • Anemia (decreased red blood cell production)
  • Cardiovascular complications (e.g., left ventricular hypertrophy (LVH), heart failure)