Ninjanerd - Chronic Kidney Disease Overview

Chronic Kidney Disease (CKD)

• CKD is a progressive loss of renal function, characterized by a reduction in Glomerular Filtration Rate (GFR) and an increase in proteinuria, particularly albuminuria.
• CKD is often caused by glomerulosclerosis, which leads to a progressive loss of nephrons and a decrease in renal function.
• Glomerulosclerosis is caused by a thickening of the glomerulus and Bowman's capsule, often due to excessive extracellular matrix secretion from mesangial cells.
• The most common cause of CKD is diabetic nephropathy, accounting for 40-45% of cases.
• Diabetic nephropathy is caused by chronic hyperglycemia, leading to non-enzymatic glycation and deposition of glycoproteins into the efferent arteriole.
• Non-enzymatic glycation narrows the efferent arteriole, increasing intra-glomerular blood pressure and inducing hyperfiltration.
• Hyperfiltration is a transient increase in GFR, stimulating mesangial cells to produce more extracellular matrix, ultimately leading to glomerulosclerosis.
• Diabetic nephropathy initially shows a transient increase, followed by a decrease in GFR as glomerulosclerosis advances. Albuminuria is typically an early indicator.
• The second most common cause is hypertensive nephropathy, accounting for 30-35% of cases.
• Hypertensive nephropathy results from chronic high blood pressure (≥140/90 mmHg), leading to afferent arteriole thickening and reduced glomerular blood flow.
• The thickened afferent arteriole causes ischemia to the nephron, prompting mesangial cells to produce extracellular matrix, causing glomerulosclerosis.
• Glomerulonephritis is a third common cause (10-15% of cases).
• Glomerulonephritis involves chronic glomerular inflammation, stimulating mesangial cells to produce extracellular matrix and increasing the glomerular basement membrane thickness, decreasing GFR.
• Patients with glomerulonephritis often exhibit significant proteinuria.

CKD Complications

• Metabolic Acidosis:

  • Arises from reduced GFR, impacting bicarbonate filtration/reabsorption and proton excretion.
  • Elevated blood protons and decreased bicarbonate lower blood pH.
  • Compensatory tachypnea (Kussmaul respirations) can occur.
  • Proton/potassium exchange can lead to hyperkalemia.
  • Severe acidosis causes hypotension and reduced heart contractility.

• Hyperkalemia:

  • Reduced GFR diminishes potassium filtration, increasing blood potassium levels.
  • Characteristic ECG changes (peaked T waves, prolonged PR interval, absent P waves, widened QRS complex, sine wave) elevate risk of ventricular fibrillation.

• Hypervolemia:

  • Reduced GFR leads to decreased sodium/water filtration, increasing blood volume.
  • Results in pulmonary edema, pleural effusions, and pitting peripheral edema.
  • Can exacerbate hypertension.

• Uremia:

  • Elevated waste products in the bloodstream cause diverse clinical manifestations.
  • Can cause altered mental status (AMS), lethargy, confusion, and coma.
  • Asterixis (flapping tremor) is a potential symptom.
  • Pericarditis (chest pain, friction rub, pericardial effusion, diffuse ST elevation with PR depression on ECG) is possible.
  • Platelet dysfunction increases bleeding risk.

• Secondary Hypertension:

  • Reduced GFR stimulates juxtaglomerular (JG) cells to release renin.
  • Renin converts angiotensinogen to angiotensin I, then to angiotensin II by ACE.
  • Angiotensin II causes vasoconstriction, elevating blood pressure.
  • Also stimulates ADH and aldosterone release, causing fluid retention and further increasing blood pressure.

• Anemia of CKD:

  • Reduced erythropoietin (EPO) production by peritubular cells, coupled with elevated hepcidin levels, lowers iron absorption and macrophage iron release.
  • Inflammation boosts hepcidin levels.
  • Fatigue, dyspnea, and palpitations are possible symptoms.

• Hyperparathyroidism:

  • Can be secondary or tertiary.
  • Decreased GFR in CKD raises phosphate levels, reduces Vitamin D production, and triggers hypocalcemia
  • Secondary: Low calcium prompts the parathyroid glands to release more PTH.
  • Tertiary: In advanced CKD, hyperplastic and autonomous parathyroid glands cause persistent high PTH levels.
  • Tertiary Hyperparathyroidism can lead to bone disease (osteitis fibrosa cystica, osteopenia, osteoporosis, pathological fractures) and calciphylaxis (vascular calcification, tissue ischemia, painful ulcers).

• Hyperlipidemia:

  • Low albumin levels in CKD stimulate liver lipoprotein production (LDL, VLDL), increasing risk of atherosclerosis and cardiovascular disease.
  • Inflammation and endothelial dysfunction contribute to atherosclerosis.

CKD Diagnosis

• GFR: GFR < 60 mL/min/1.73 m² for ≥ 3 months signifies CKD.
• Albuminuria: Urine albumin-to-creatinine ratio indicates CKD severity.
  • <30: Mild
  • 30-300: Microalbuminuria

  • 300: Macroalbuminuria

• Renal Ultrasound: May show hyper-echogenicity, cortical thinning, and smaller kidney size (non-specific).
  • Also identifies conditions like polycystic kidney disease (PKD), characterized by enlarged kidneys with cysts.
• Urinalysis with Microscopy: Broad waxy casts indicate chronic kidney injury.

CKD Treatment

• Metabolic Acidosis:

  • Prevent: Low-phosphate diet.
  • Treat: Phosphate binders, calcitriol (if calcium and Vitamin D low), calcium chelators, or parathyroidectomy (for tertiary hyperparathyroidism).

• Hyperkalemia:

  • Prevent: Low-potassium diet.
  • Treat: Loop diuretics, potassium-binding resins.

• Hypervolemia:

  • Prevent: Sodium restriction.
  • Treat: Loop diuretics.

• Uremia (Waste buildup):

  • Treat with dialysis (hemodialysis, peritoneal dialysis).

• Secondary Hypertension:

  • Treat: ACE inhibitors or ARBs.

• Anemia of CKD:

  • Treat: Iron supplementation (if deficient), erythropoietin (EPO) therapy.

• Hyperparathyroidism:

  • Prevent: Low-phosphate diet.
  • Treat: Phosphate binders, calcitriol, calcium chelators, or parathyroidectomy (for tertiary hyperparathyroidism).

CKD Stage Progression

• CKD Stage 3A: GFR 45-59 mL/min/1.73 m²
• CKD Stage 3B: GFR 30-44 mL/min/1.73 m²
• CKD Stage 4: GFR 15-29 mL/min/1.73 m²
• CKD Stage 5 (End-Stage Renal Disease): GFR < 15 mL/min/1.73 m²

CKD Treatment Considerations

• Iodine Contrast: Avoid in CKD patients (GFR < 60 mL/min/1.73 m²) due to contrast-induced nephropathy risk.
• Gadolinium Contrast: Avoid in CKD patients (GFR < 30 mL/min/1.73 m²) due to nephrogenic systemic fibrosis risk.
• Drug Dosing: Adjust medications for renal function to prevent toxicity.

Dialysis Access Options

• Hemodialysis:

  • AV Fistula: Preferred long-term access, low infection risk, but requires 4-6 weeks to mature.
  • AV Graft: Alternative, faster maturation, higher risk of stenosis, thrombosis, and graft failure.
  • Central Venous Catheter: Urgent/emergent use, high infection risk.

• Peritoneal Dialysis: Uses implanted peritoneal catheter.

Dialysis Complications

• Hypotension: Can occur during hemodialysis.
• Dialysis Disequilibrium Syndrome: Rapid urea removal causing cerebral edema and symptoms (headache, nausea, vomiting).
• Access Complications:
  • Central Venous Catheters: High infection risk.
  • AV Grafts: Stenosis and clotting risk.
  • Peritoneal Dialysis: Peritonitis risk.

Kidney Transplantation

• Considered for End-Stage Renal Disease (ESRD), typically on the left side due to longer renal vein.