What is the recommended management of chronic kidney disease–mineral and bone disorder in adults with CKD stages 3–5, including dialysis?

Management of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD)

Base all treatment decisions on serial monitoring of phosphate, calcium, and PTH levels considered together, not on isolated laboratory values, as these biomarkers interact to predict cardiovascular risk and mortality. 1

Monitoring Strategy

CKD Stages 3a-5 (Not on Dialysis)

• Phosphate and calcium: Monitor every 6-12 months in CKD G3a-G3b; every 3-6 months in CKD G4; every 1-3 months in CKD G5 1
• PTH: Monitor once initially in CKD G3a-G3b, then based on baseline level and CKD progression; every 6-12 months in CKD G4; every 3-6 months in CKD G5 1
• Alkaline phosphatase: Annually or more frequently if PTH is elevated 1

CKD Stage 5D (Dialysis)

• All parameters: Monitor at least weekly until stable, then adjust frequency based on trends 1

Phosphate Management

Lower elevated phosphate levels toward the normal range through dietary restriction, phosphate binders, and intensified dialysis. 1

Dietary Approach

• Restrict dietary phosphate intake as first-line therapy 1
• Consider phosphate source (animal, vegetable, additives) when making dietary recommendations, as bioavailability differs 1

Phosphate Binders

• Initiate only for progressively or persistently elevated serum phosphate, not for normal levels 1
• Restrict the dose of calcium-based phosphate binders in adults with CKD G3a-G5D 1
• Further restrict calcium-based binders in the presence of: 1
  • Arterial calcification
  • Adynamic bone disease
  • Persistently low PTH levels
• Avoid aluminum-containing phosphate binders long-term due to toxicity risk 1

Dialysis Optimization

• Increase dialytic phosphate removal for persistent hyperphosphatemia in CKD G5D 1

Critical Caveat

A recent trial showed that phosphate binders in CKD G3b-G4 patients with normal phosphate levels increased coronary calcification without lowering FGF23, fundamentally changing the approach from the 2009 guidelines 1. Do not treat normal phosphate levels prophylactically.

Calcium Management

Avoid hypercalcemia in all adult patients with CKD G3a-G5D. 1

• Use dialysate calcium concentration between 1.25-1.50 mmol/L (2.5-3.0 mEq/L) in CKD G5D 1
• Higher calcium concentrations are associated with increased mortality and cardiovascular events 1
• The 2017 guideline abandoned the previous recommendation to correct hypocalcemia, as hypercalcemia poses greater risk 1

PTH Management

CKD Stages 3a-5 (Not on Dialysis)

The optimal PTH level is unknown, but evaluate patients with progressively rising or persistently elevated PTH above the upper normal limit for modifiable factors. 1

Evaluation and Initial Management

When PTH is elevated, assess and correct: 1

• Hyperphosphatemia (reduce dietary phosphate, add phosphate binders)
• Hypocalcemia (calcium supplements if needed)
• High phosphate intake (dietary counseling)
• Vitamin D deficiency (native vitamin D supplementation)

Active Vitamin D Therapy

Do NOT routinely use calcitriol or vitamin D analogs in adults with CKD G3a-G5 not on dialysis. 1

• Reserve calcitriol and vitamin D analogs only for patients with CKD G4-G5 with severe and progressive hyperparathyroidism despite correction of modifiable factors 1
• This represents a major shift from 2009 guidelines, which recommended earlier use 1
• Recent meta-analysis showed vitamin D therapy probably has no effect on all-cause death and uncertain effects on fracture and cardiovascular outcomes 2

CKD Stage 5D (Dialysis)

Maintain intact PTH levels in the range of approximately 2 to 9 times the upper normal limit for the assay. 1

• Initiate or change therapy when marked PTH changes occur in either direction to prevent progression outside this range 1

PTH-Lowering Therapy Options

For patients requiring PTH-lowering therapy, use calcimimetics, calcitriol, vitamin D analogs, or a combination of calcimimetics with calcitriol or vitamin D analogs—no single agent is prioritized. 1

• All options are acceptable first-line therapies 1
• Although the EVOLVE trial did not meet its primary endpoint, the majority of evidence supports potential benefits of calcimimetics in G5D patients 1

Parathyroidectomy

• Consider parathyroidectomy for severe hyperparathyroidism failing medical/pharmacological therapy in CKD G3a-G5D 1

Cardiovascular Risk Assessment

Patients with known vascular or valvular calcification should be considered at highest cardiovascular risk. 1

• Use lateral abdominal radiograph to detect vascular calcification 1
• Use echocardiogram to detect valvular calcification 1
• Use this information to guide more aggressive CKD-MBD management 1

Bone Disease and Fracture Risk

CKD Stages 1-2

• Manage osteoporosis and high fracture risk as for the general population 1

CKD Stages 3a-3b

• If PTH is in the normal range with osteoporosis/high fracture risk, treat as for the general population 1

CKD Stages 3a-5D with Biochemical Abnormalities

• Treatment choices must account for the magnitude and reversibility of biochemical abnormalities and CKD progression 1
• Consider bone biopsy before initiating anti-osteoporotic therapy when biochemical abnormalities of CKD-MBD are present 1

Key Paradigm Shifts from 2009 Guidelines

The 2017 KDIGO update fundamentally changed several recommendations: 1

1. Abandoned target ranges for phosphate and calcium in favor of avoiding extremes
2. No prophylactic phosphate binder use in patients with normal phosphate levels
3. Calcitriol/vitamin D analogs NOT routinely used in non-dialysis CKD
4. Emphasis on avoiding hypercalcemia rather than correcting hypocalcemia
5. Treatment based on trends of multiple biomarkers together, not single values