Regarding CKD mineral and bone disorder (CKD-MBD), the earliest metabolic derangement that appears even in CKD Stage 2 (eGFR 60–89), before any change in serum calcium or phosphorus, is:

• A Elevated serum phosphorus
• B Elevated FGF-23 (fibroblast growth factor 23) ✓
• C Decreased 1,25-dihydroxyvitamin D (calcitriol)
• D Elevated PTH

Explanation

FGF-23 rises earliest in CKD progression — detectable even at eGFR >60 mL/min — as a compensatory response to maintain phosphorus homeostasis by promoting phosphaturia and suppressing 1-alpha hydroxylase. This precedes elevations in PTH, phosphorus, or falls in calcitriol. Suppressed 1,25(OH)2D follows FGF-23-mediated 1-alpha hydroxylase inhibition. Elevated PTH appears later as calcitriol falls and serum calcium drops. Hyperphosphataemia is a late finding (usually eGFR <30). Elevated FGF-23 is independently associated with increased cardiovascular mortality in CKD.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.