Project Details
Description
PROJECT SUMMARY
Since 1988, 154,944 living individuals in the US have donated a kidney. In 2018 alone, 6,446 living donor
kidney transplants were performed in the US from a total of 16,313 transplants. To make informed decisions
about kidney donation, living donors must be aware of potential risks associated with organ donation. The
effects of kidney donation upon skeletal health are not well-defined. Living kidney donors may potentially have
an increased risk of fractures due to reductions in renal mass and glomerular filtration rate (GFR) and
concentrations of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), and secondary increases in parathyroid
hormone (PTH) and bone turnover. The scientific premise of our application is based on observations from a
prospective study, in which we demonstrated that 6 and 36 months after donation, kidney donors had
significantly higher serum (s) intact PTH and fibroblast growth factor-23 (FGF-23) concentrations, and reduced
s1,25(OH)2D, phosphate (Pi) concentrations, and tubular Pi reabsorption compared to healthy controls. Higher
concentrations of bone resorption and formation markers were observed in donors compared to healthy
controls. Preliminary data from the Rochester Epidemiology Project show a 2-3-fold excess risk of fractures
and a 3-fold excess risk of osteoporosis in individuals who had a nephrectomy compared to control subjects.
The studies suggest that bone quality may be impaired in kidney donors predisposing them to fractures. We
hypothesize that reductions in renal mass and GFR following kidney donation result in a decrease in
s1,25(OH)2D and an increase in sPTH and sFGF-23 concentrations, which in turn contribute to increased bone
turnover, reductions in bone density and strength and risk of fractures. To test our hypothesis, we propose two
aims. In AIM 1, we will compare the risk of fractures among 3000 living kidney donors with the risk of fractures
in a group of age-, sex-, race-, and comorbidity-matched subjects who would have been eligible to donate but
did not donate a kidney. In AIM 2 we will assess skeletal health in 200 kidney donors who are ≥10 years after
kidney donation and are ≥50 years of age by measuring areal bone mineral density at the lumbar spine, hip
and forearm; skeletal architecture and strength by peripheral high-resolution micro-computed tomography and
finite element analysis; and serum mineral and bone biomarkers. For comparison, we will examine 200 age-,
sex-, race- and comorbidity-matched controls that have not donated a kidney, but would have been healthy
enough to donate. Our studies will provide important, previously unavailable information, regarding the risk of
fractures in a large cohort of kidney donors, and will identify mechanisms by which skeletal complications
occur. An observed increase in fractures amongst kidney donors will change medical practice by supporting
evaluation of abnormalities in mineral metabolism and skeletal integrity in donors. Therapy of disordered
mineral metabolism with 1α-hydroxylated vitamin D analogs would be indicated. Conversely, demonstration of
an absence of increased fractures amongst donors will reassure kidney donors of the safety of donation.
Status | Finished |
---|---|
Effective start/end date | 7/9/20 → 4/30/23 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $671,075.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $703,895.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $675,043.00
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