Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation

Area of Science:

• Nephrology
• Endocrinology
• Bone Metabolism

Background:

• Persistent secondary hyperparathyroidism and hypercalcemia are common post-kidney transplant.
• The underlying bone disease mechanisms in these patients remain incompletely understood.
• Previous studies have not utilized bone biopsies to investigate this condition.

Purpose of the Study:

• To investigate the bone histomorphometry and associated biochemical markers in hypercalcemic patients post-kidney transplantation.
• To determine the relationship between bone turnover, calcium and phosphate levels, and hyperparathyroidism in this cohort.

Main Methods:

• Bone biopsies with double tetracycline labeling were performed on 17 hypercalcemic kidney transplant recipients (eGFR > 30 mL/min/1.73 m2).
• Measurements included serologic bone markers, calcitriol, intact fibroblast growth factor-23 (iFGF-23), serum/urine calcium and phosphate.
• Calculated parameters included tubular maximum for phosphate corrected for GFR (TmP/GFR) and fractional excretion of calcium (FeCa).

Main Results:

• High-turnover renal osteodystrophy (ROD) was found in 9 patients, and low-turnover ROD in 8 patients.
• Bone formation rate correlated significantly with bone alkaline phosphatase, c-telopeptide, and osteocalcin.
• Fractional excretion of calcium was normal or low in 14/17 patients, and TmP/GFR was universally low.
• Neither intact parathyroid hormone (PTH) nor iFGF-23 correlated with TmP/GFR, FeCa, or bone histomorphometry.

Conclusions:

• Hypercalcemia in persistent secondary hyperparathyroidism after kidney transplantation can be associated with either high or low bone turnover.
• Reduced renal calcium excretion appears to be a significant factor contributing to hypercalcemia in these patients.
• These findings highlight the complex pathophysiology of bone disease post-transplantation.