Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation

Abstract

In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared to matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products (AGEs) in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < 0.001), increases in both parathyroid hormone (PTH when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = 0.03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < 0.001) and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency towards thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.