Pathophysiology
Clinical meaning
Chronic kidney disease disrupts multiple metabolic processes, causing predictable complications that worsen as GFR declines. Anemia of CKD results from decreased erythropoietin (EPO) production by peritubular fibroblasts (EPO stimulates bone marrow RBC production), reduced RBC survival in the uremic environment, and iron deficiency from poor dietary absorption and chronic inflammation. Mineral and bone disorder (CKD-MBD) involves hyperphosphatemia (impaired renal phosphorus excretion), hypocalcemia (from hyperphosphatemia binding calcium and impaired renal activation of vitamin D), secondary hyperparathyroidism (PTH elevation driving bone resorption), and renal osteodystrophy (weakened bones prone to fractures). Metabolic acidosis occurs because the kidneys cannot regenerate bicarbonate or excrete hydrogen ions adequately; acidosis accelerates CKD progression, worsens hyperkalemia (hydrogen-potassium exchange), and causes protein catabolism with muscle wasting. Uremic toxin accumulation affects multiple organs: cardiovascular (accelerated atherosclerosis, pericarditis), neurological (peripheral neuropathy, encephalopathy, asterixis), gastrointestinal (nausea, metallic taste, uremic fetor), dermatological (pruritus, uremic frost in severe cases), and immunological (impaired immunity increasing infection risk).