Kidney donors with mild reductions in renal function display abnormal levels of bone biomarkers for 3 years after donation, according to a new study.
For the ALTOLD (Assessing Long Term Outcomes in Living Kidney Donors) study, a team led by Bertram L. Kasiske, MD, of Hennepin County Medical Center in Minneapolis, and Rajiv Kumar, MD, of Mayo Clinic in Rochester, Minnesota, prospectively compared markers of mineral and bone metabolism in 182 kidney donors (unilateral nephrectomy) and 173 healthy controls suitable for donation matched by age and gender.
At 6 and 36 months after donation, donors had significantly higher serum levels of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor 23 (9.5% and 8.4%) compared with controls. They also had increased phosphate excretion reflected by reduced tubular phosphate reabsorption (–7.0% and –5.0%) and serum phosphate concentrations (–6.4% and –2.3%). Such phosphate wasting may be an attempt to maintain normal phosphate levels, according to an accompanying editorial.
Serum calcitriol (1,25-dihydroxyvitamin D3) concentrations were significantly lower in donors (–17.1% and –12.6%) at the same time points, whereas 25-hydroxyvitamin D concentrations were significantly higher (21.4% and 19.4%). The investigators observed no alterations in calcium. Together, the findings suggest reduced glomerular filtration rate and calcitriol synthesis, resulting in secondary hyperparathyroidism.
In addition, the investigators observed increased bone turnover markers in donors. At 6 and 36 months, they found significantly higher concentrations of the bone resorption markers carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%). They also saw increases in bone formation markers: osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%).
The findings possibly indicate impaired bone metabolism in kidney donors. “Elevated PTH concentrations occurring as a result of reduced 1,25(OH)2D3 synthesis and attendant negative calcium balance could serve as the driver of altered bone metabolism and osteocyte activity following kidney donation,” Dr Kasiske, Dr Kumar, and colleagues wrote in Kidney International (2016;90:734-736). The possible effects of increased Klotho expression were not assessed and merit further study.
Alternately, the findings simply may reflect slow renal clearance of these biomarkers. The authors of an accompanying editorial emphasized this point, suggesting that future research examine bone mass and microarchitecture via imaging and fracture incidence.
“It is our obligation to correctly inform and carefully evaluate candidate kidney donors and provide intensive and lifelong monitoring after donor nephrectomy for incident chronic kidney, disturbances of mineral and bone metabolism, and cardiovascular disease,” stated Pieter Evenepoel, MD, PhD, and Maarten Naesens, MD, PhD, of University Hospitals Leuven in Belgium.
1. Kasiske BL, Kumar R, and Kimmel PL. Abnormalities in biomarkers of mineral and bone metabolism in kidney donors. Kidney Intl (2016) 90, 861–868. doi: 10.1016/j.kint.2016.05.012.
2. Evenepoel P and Naesens M. Mineral metabolism disturbances in kidney donors: smoke, no fire (yet). Kidney Int (2016) 90, 734–736. doi: 10.1016/j.kint.2016.07.001.