Kidney Transplantation Followed by Drop in Sclerostin Levels

Improved renal function contributes to decline in a glycoprotein that inhibits bone formation.
Improved renal function contributes to decline in a glycoprotein that inhibits bone formation.

Markedly elevated blood levels of sclerostin in patients with end-stage renal disease (ESRD) decrease rapidly to normal or subnormal values after renal transplantation, a new study suggests.

Sclerostin is a glycoprotein secreted by osteocytes and which inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and ESRD.

A team led by Rudolf P. Wüthrich, MD, measured sclerostin levels by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year following transplantation. Pre-transplant levels were elevated in all subjects, who had a mean level of 61.8 pmol/L (20-30 pmol/L is the normal range).

Within 15 days after transplantation—and correlating with improvement in renal function—sclerostin levels dropped to 21 pmol/L and then increased to 23.8 and 28.0 after 6 and 12 months, respectively,  Dr. Wüthrich and his colleagues reported in Kidney & Blood Pressure Research (2014;39:230-239).

“The inhibition of sclerostin might be a promising therapeutic strategy for the preservation of bone mass,” the researchers concluded.

Antibodies targeting sclerostin are being developed for the treatment post-menopausal osteoporosis, showing increased bone growth in preclinical studies, they noted.

One possible explanation for the decline in sclerostin after transplantation is improvement in renal function that leads to better clearance of sclerostin, the researchers stated. In addition, the authors pointed out that mechanical stress on the skeleton is known to decrease production of sclerostin, and this could contribute to higher sclerostin levels in patients on dialysis, who often have decreased physical activity.

“Given the fact that patients are physically more active after renal transplantation this could translate to lower sclerostin levels after transplantation,” they wrote. Lastly, the use of glucocorticoids after transplantation could contribute to a rapid decrease of sclerostin.

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