Abnormalities in biomarkers of mineral and bone metabolism in kidney donors

Abstract

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (−7.0% and −5.0%) and serum phosphate concentrations (−6.4% and −2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (−17.1% and −12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%,) concentrations were significantly higher in donors compared to controls. Moreover, 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%), and the bone formation markers, osteocalcin (26.3% and 2.7%), and procollagen type I N-terminal propetide (24.3% and 8.9%) were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors.

Changes in Markers of Mineral Metabolism After Living Kidney Donation

“…The biochemical variations observed in this study after kidney donation are largely concordant with prior prospective reports 16,17,23,24 though most of these prior studies lacked comparator groups and investigated acute changes within the first week after surgery which our study did not. T 1 was selected as an optimal study timepoint to avoid acute postoperative changes (eg, within the first week) that could add to confounding and recalibration of mineral parameters was anticipated by T 1 .…”

“…24 Given the small absolute differences in PTH documented, it is not surprising that the difference is not significant in our study. Simple sample size calculations to detect a true difference of 1pmol/L with 80% power would suggest a minimum of 222 matched pairs would be required.…”

“…The larger ALTOLD study has also reported similar uPi findings after donor nephrectomies however these assessments were limited to spot morning urine collections. 24 …”

Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage

“…These changes include a decline in the serum concentration of 1, 25-dihydroxyvitamin D and phosphate, a decline in tubular phosphate reabsorption, and a rise in the concentration of serum PTH. 139,201,202,208 For example, one study showed that kidney donors had higher serum concentrations of fibroblast growth factor-23 and greater fractional excretion of inorganic phosphate compared with nondonor controls. 209 The Assessing Long Term Outcomes of Living Donation prospective cohort study found a 23% higher PTH concentration among 206 donors assessed at 6 months postdonation compared with concentrations among 198 healthy controls (52.7 vs 42.8 pg/mL, respectively) 201 that persisted at 36-month follow-up.…”

Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation Kidney Disease

“…The overall cardiovascular impact of the modest decline in whole-kidney GFR in an otherwise healthy adult is uncertain, but some prospective controlled studies have suggested that such alterations might have an effect on left ventricular mass even independent of blood pressure in otherwise healthy donors [ 18 , 19 ]. Other asymptomatic biochemical abnormalities, including elevations in fibroblast growth factor 23 and other biomarkers of mineral and bone metabolism, have also be observed [ 21 ].…”