What is CKD-Mineral and Bone Disorder (CKD-MBD)?

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), previously known as Renal Osteodystrophy, is a systemic disorder of mineral and bone metabolism that occurs as a complication of chronic kidney disease (CKD). It involves abnormalities in calcium, phosphorus, parathyroid hormone (PTH), and Vitamin D metabolism, leading to bone disease and vascular calcification.

Why Does it Happen?

Healthy kidneys play a critical role in maintaining bone and mineral balance:

• Activate Vitamin D: Kidneys convert Vitamin D to its active form (calcitriol), which helps absorb calcium from the gut
• Excrete Phosphorus: Kidneys remove excess phosphorus

When kidneys fail:

1. Phosphorus Builds Up (Hyperphosphatemia): Kidneys can't excrete it → high phosphorus binds calcium → low calcium
2. Low Calcitriol (Active Vitamin D): Kidneys can't produce it → reduced calcium absorption from gut → low calcium
3. Low Calcium (Hypocalcemia): From above two mechanisms
4. Secondary Hyperparathyroidism: Parathyroid glands overproduce PTH in response to low calcium and high phosphorus → PTH pulls calcium from bones → weakens bones
5. Bone Disease: High PTH causes bone turnover abnormalities
6. Vascular Calcification: Excess calcium-phosphate deposits in blood vessels, heart valves → cardiovascular disease

Types of Renal Osteodystrophy (Bone Disease):

1. High-Turnover Bone Disease (Osteitis Fibrosa Cystica):

• Most common type
• Caused by high PTH
• Rapid bone resorption and formation (but disorganized)
• Bones are weak, prone to fractures

2. Low-Turnover Bone Disease (Adynamic Bone Disease):

• Low or normal PTH
• Bone cells are "inactive"—little bone formation or resorption
• Can occur from over-suppression of PTH (too much Vitamin D or calcimimetics)
• Bones are brittle, prone to fractures

3. Osteomalacia:

• Defective bone mineralization (soft bones)
• From severe Vitamin D deficiency or aluminum toxicity (rare now—from aluminum-containing antacids or dialysate)

4. Mixed Bone Disease:

• Features of both high and low turnover

Symptoms:

• Bone Pain, Fractures
• Muscle Weakness
• Bone Deformities: In children → growth retardation, bowing of legs (rickets)
• Itching (Pruritus): From high phosphorus
• Vascular Calcification: Cardiovascular disease, heart attacks, strokes (often silent until late)
• Calciphylaxis: Rare but life-threatening; calcium deposits in skin/soft tissues → painful skin ulcers, necrosis

Diagnosis:

Labs (Monitor Regularly in CKD Patients):

• Calcium: Often low or low-normal
• Phosphorus: Elevated (especially in advanced CKD)
• PTH (Intact PTH):
  • Secondary Hyperparathyroidism: PTH elevated (often 2-9x normal in CKD stages 3-5)
  • Target PTH varies by CKD stage (stage 5/dialysis: 2-9x upper limit of normal; not fully normalized)
• 25-OH Vitamin D: Often low (supplement to >30 ng/mL)
• Alkaline Phosphatase (Bone-Specific): Reflects bone turnover
• Calcium x Phosphorus Product: Goal <55 mg²/dL² (high product → increased vascular calcification risk)

Imaging:

• Bone X-rays: Subperiosteal resorption (especially fingers), bone cysts, fractures
• DEXA Scan: Assess bone density (though may not accurately reflect bone strength in CKD)
• CT or X-rays: Vascular calcification
• Bone Biopsy: Gold standard to differentiate types of bone disease (rarely done)

Treatment:

Goals:

• Control phosphorus, calcium, PTH
• Prevent/slow bone disease and vascular calcification
• Reduce fracture risk and cardiovascular mortality

1. Control Phosphorus:

• Dietary Restriction: Low-phosphorus diet (avoid dairy, processed foods, cola)
• Phosphate Binders: Taken with meals to prevent phosphorus absorption
  • Calcium-based: Calcium carbonate, calcium acetate (avoid if hypercalcemia)
  • Non-calcium-based (preferred): Sevelamer (Renagel®/Renvela®), lanthanum (Fosrenol®), iron-based (Auryxia®)
• Goal Phosphorus: 3.5-5.5 mg/dL (CKD stage 5/dialysis)

2. Vitamin D Supplementation:

• Nutritional Vitamin D (Cholecalciferol/D3): For deficiency (25-OH D <30 ng/mL)
• Active Vitamin D (Calcitriol or Analogs): For secondary hyperparathyroidism
  • Calcitriol (Rocaltrol®), paricalcitol (Zemplar®), doxercalciferol (Hectorol®)
  • Suppresses PTH, increases calcium absorption
  • Risk: Hypercalcemia, hyperphosphatemia

3. Calcimimetics:

• Cinacalcet (Sensipar®): Oral medication that makes parathyroid glands more sensitive to calcium → lowers PTH
• Etelcalcetide (Parsabiv®): IV for dialysis patients
• Used if PTH remains high despite other treatments
• Risk: Hypocalcemia

4. Parathyroidectomy (Surgery):

• For severe, refractory secondary hyperparathyroidism (very high PTH unresponsive to medical therapy)
• Removes overactive parathyroid glands
• Risk: Post-op hungry bone syndrome (severe hypocalcemia)

5. Dialysis:

• Removes phosphorus (but not as effectively as healthy kidneys)
• Dialysate calcium concentration adjusted to balance calcium levels

6. Kidney Transplant:

• Definitive treatment; restores kidney function
• Reverses CKD-MBD abnormalities over time

Monitoring (CKD Stages 3-5):

• Calcium, Phosphorus: Monthly (dialysis) or every 3-6 months (CKD 3-4)
• PTH: Every 3-6 months
• 25-OH Vitamin D: Annually
• Alkaline Phosphatase: Every 12 months or if PTH elevated

Complications:

• Fractures, bone pain, deformities
• Vascular calcification → cardiovascular disease (leading cause of death in CKD)
• Calciphylaxis (rare, often fatal)