What is the diagnosis and management of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)?

From the Guidelines

CKD-MBD management should focus on controlling phosphate, calcium, and parathyroid hormone (PTH) levels, with a comprehensive approach that includes dietary restrictions, phosphate binders, and active vitamin D analogs, as recommended by the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline update 1.

Key Components of CKD-MBD Management

• Restrict dietary phosphate to 800-1000 mg/day to decrease phosphate levels
• Use phosphate binders such as calcium-based binders (e.g., calcium carbonate 500-1500 mg with meals), sevelamer (800-1600 mg with meals), or lanthanum carbonate (500-1000 mg with meals) to maintain calcium levels
• Utilize active vitamin D analogs like calcitriol (0.25-1 mcg daily) or paricalcitol (1-2 mcg daily) to address elevated PTH levels
• Consider calcimimetics like cinacalcet (starting at 30 mg daily, titrating up to 180 mg if needed) if PTH remains elevated despite vitamin D therapy

Monitoring and Adjustments

• Regularly monitor serum calcium, phosphate, PTH, and vitamin D levels to guide therapy adjustments
• Base treatment decisions on trends in laboratory values rather than a single abnormal result, and be cautious to avoid hypercalcemia when treating secondary hyperparathyroidism 1
• Target PTH levels are typically 2-9 times the upper limit of normal for dialysis patients, with the goal of minimizing cardiovascular risk and preventing fractures and bone disease.

From the FDA Drug Label

Cinacalcet tablets are not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia [see Warnings and Precautions (5.1)]. The FDA drug label does not answer the question about CKD MBD management directly, but it does mention that cinacalcet is indicated for the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease (CKD) on dialysis.

• The recommended starting oral dose of cinacalcet tablets is 30 mg once daily for patients with CKD on dialysis.
• Hypocalcemia is a potential risk of cinacalcet treatment, and serum calcium levels should be monitored frequently during dose titration.
• Cinacalcet can be used alone or in combination with vitamin D sterols and/or phosphate binders.
• The safety and effectiveness of cinacalcet have not been established in patients with CKD not on dialysis, and the long-term safety and efficacy of cinacalcet in these patients have not been established 2.

From the Research

Definition and Management of CKD-MBD

• CKD-MBD is a systemic disorder characterized by abnormalities in bone biopsy, laboratory parameters, and/or vascular or other soft-tissue calcifications 3, 4, 5.
• The management of CKD-MBD aims to maintain normal levels of serum calcium, phosphorus, and parathyroid hormone (PTH) to prevent complications such as bone disease, vascular calcification, and cardiovascular disease 3, 4, 6.

Phosphate Binders in CKD-MBD Management

• Phosphate binders are used to reduce serum phosphate levels and prevent the progression of CKD-MBD 3, 4, 6.
• Different types of phosphate binders, such as sevelamer, lanthanum, iron-based binders, and calcium-based binders, have been compared in terms of their efficacy and safety 6.
• Sevelamer may lead to lower death rates and less hypercalcaemia compared to calcium-based binders in patients with CKD G5D 6.

Vitamin D and Calcimimetics in CKD-MBD Management

• Vitamin D derivatives and selective vitamin D receptor activators are used to improve vitamin D deficiency and control PTH levels 4, 7.
• Calcimimetics, such as cinacalcet, are used to control PTH levels and prevent hyperparathyroidism 5, 7.
• The use of calcimimetics in pediatric patients is limited, and more studies are needed to define their role in the treatment of CKD-MBD in children 4.

Treatment Goals and Outcomes

• The treatment goals for CKD-MBD include maintaining normal levels of serum calcium, phosphorus, and PTH, and preventing complications such as bone disease, vascular calcification, and cardiovascular disease 3, 4, 6.
• The effects of phosphate binders on patient-important outcomes, such as death, cardiovascular disease, and bone fractures, are uncertain and require further study 6.