25-Year Risk of Fracture Among Living Kidney Donors

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https://www.docwirenews.com/post/25-year-risk-of-fracture-among-living-kidney-donors

25-Year Risk of Fracture Among Living Kidney Donors
By Victoria Socha

Worldwide, the prevalence of living kidney donation is increasing; approximately 30,000 individuals become living donors each year. In the United States, of 459,849 transplants performed, 187,194 individuals have donated a kidney. In 2022, 29.2% of kidney transplants performed in the United States were from living donors.


According to Hilal Maradit Kremers, MD, and colleagues, there are health risks to the donor associated with living kidney donation. While the 15-year observed risk of end-stage kidney disease in kidney donors is low, it is reported to be 3.5 to 5.3 times higher than the projected risk in the absence of donation. Results of previous studies of markers of mineral and bone metabolism among kidney donors following kidney donation have suggested that bone quality may be impaired in kidney donors, due to reductions in kidney mass, lower concentrations of serum 1,25 dihydroxyvitamin D, and secondary increases in serum parathyroid hormone.
Dr. Kremers et al conducted a survey-based study designed to compare the overall and site-specific risk of fracture among living kidney donors. The survey included strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Results of the study were reported in JAMA Network Open.
The study exposure was living kidney donation. The primary outcome of interest was a comparison of the rates of overall and site-specific fractures between living kidney donors and controls. Standardized incidence ratios (SIRs) were used in the comparison.
The survey was conducted between December 1, 2021, and July 31, 2023. Living donors (n=5065) at three large transplant centers in Minnesota were invited to participate in a survey regarding their bone health and history of fractures. Using the Rochester Epidemiology Project database, the researchers invited a nondonor control population of 16,156 individuals with no history of comorbidities to complete the same survey.
Survey questions were derived from validated surveys used in the National Health and Nutrition Examination Survey, Framingham Study, Women’s Health Initiative, Study of Osteoporotic Fractures, and the Nurses’ Health Study. The survey included questions on bone health and fracture history, self-reported race and ethnicity, height, weight, smoking, alcohol use, menstrual status, self-reported osteoporosis diagnosis, and use of medications known to interfere with mineral metabolism.
A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Of the 2132 donors who responded, mean age was 67.1 years and 58.4% (n=1245) were female. Of the 2014 controls, mean age was 68.6 years and 56.6% (n=1140) were female. There was substantial variation in participation rates between the two groups: 42.1% (2131/5065) of donors responded versus 12.5% (2014/16,156) of controls. There were also variations in participation rates by age (rates were similarly highest among individuals 67 to 72 years of age for both donors and controls). Participation rates were highest among White participants compared with those of a racial or ethnic minority group or unknown race. Rates varied across donation medical centers as well.
Forty-two donors and 137 controls were excluded from analyses due to incomplete survey data. All further analyses comparing the observed and expected number of fractures were limited to the 2090 donors and 1877 controls with complete information on fractures. Among the final analysis cohort, mean time between donation or index date and completion of the survey was 24.2 years for donors and 27.6 years for controls. Controls were 1.5 years older than the donors (68.6 years vs 67.1 years).
Among the 2090 donors, the rate of all types of fractures was significantly lower than among the 1877 controls: 443.0 observed versus 499.8 expected fractures (SIR, 0.89; 95% CI, 0.81-0.97; P=.009). However, there were significantly more vertebral fractures among donors than among controls: 51 observed versus 36 expected vertebral fractures (SIR, 1.42; 95% CI, 1.05-1.83; P=.02). Among men, there were 21.0 observed vertebral fractures versus 12.5 expected (SIR, 1.67; 95% CI, 1.04-2.47; P=.04).
Results of two separate validation studies among the controls demonstrated that controls who returned surveys were similar to controls who did not return surveys in terms of frequency and types of fractures. The fracture survey instrument was validated among a random sample of 332 controls who returned surveys (166 who reported any fracture and 166 who reported no fractures). Overall agreement of fractures reported on the survey versus fractures found by a nurse in the complete historical medical records was good (89.5% raw agreement). The agreement was better than would be expected by chance alone.
The researchers cited some limitations to the study findings, including the historical nature of the study that resulted in an inability to screen nondonor controls for factors such as laboratory test and imaging results that would have precluded kidney donation. Other limitations included the inability to conduct stratified analyses by race and ethnicity due to small numbers of those groups, and the possibility of inaccurate recall among participants of the exact timing of fractures.
In summary, the authors said, “In this survey-based study, we observed a reduction in overall fractures but an excess risk of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.”
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814233

Original Investigation Nephrology
January 24, 2024
Fracture Risk Among Living Kidney Donors 25 Years After Donation
Hilal Maradit Kremers, MD1,2; Brandon R. Grossardt, MS3; Adam R. Miller, BS4; et al
Bertram L. Kasiske, MD5; Arthur J. Matas, MD6; Sundeep Khosla, MD7,8; Walter K. Kremers, PhD3; Hatem Amer, MD4,9; Rajiv Kumar, MBBS9,10
Author Affiliations Article Information
JAMA Netw Open. 2024;7(1):e2353005. doi:10.1001/jamanetworkopen.2023.53005


Key Points
Question  What is the long-term risk of overall and site-specific fractures among living kidney donors?
Findings  In this survey study that included 2132 living kidney donors and 2014 controls, the overall rate of fractures was significantly lower among donors than controls. However, there were significantly more vertebral fractures among donors than controls.
Meaning  This study suggests that, although the overall fracture rate among donors was low, reductions in kidney mass and prolonged hyperparathyroidism may predispose living kidney donors to trabecular bone loss and vertebral fractures.
Abstract
Importance  Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone.
Objective  To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so.
Design, Setting, and Participants  This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023.
Exposure  Living kidney donation.
Main Outcomes and Measures  The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs).
Results  At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83).
Conclusions and Relevance  This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.