TY - JOUR
T1 - Kidney Transplantation, Immunosuppression and the Risk of Fracture
T2 - Clinical and Economic Implications
AU - Kuppachi, Sarat
AU - Cheungpasitporn, Wisit
AU - Li, Ruixin
AU - Caliskan, Yasar
AU - Schnitzler, Mark A.
AU - McAdams-DeMarco, Mara
AU - Ahn, Ji Yoon B.
AU - Bae, Sunjae
AU - Hess, Gregory P.
AU - Segev, Dorry L.
AU - Lentine, Krista L.
AU - Axelrod, David A.
N1 - Funding Information:
Sarat Kuppachi, MBBS, Wisit Cheungpasitporn, MD, Ruixin Li, MS, Yasar Caliskan, MD, Mark A. Schnitzler, PhD, Mara McAdams-DeMarco, PhD, JiYoon B. Ahn, PhD, Sunjae Bae, PhD, Gregory P. Hess, MD, Dorry L. Segev, MD, PhD, Krista L. Lentine, MD, PhD, and David A. Axelrod, MD, MBA, KLL and DAA are co-senior authors (contributed equally). Study design: KLL, DAA, SK, WC, YC, MAS, MM-D, DLS, JBA, SB, GPH; data acquisition: KLL, MAS; data analysis: RL; data interpretation: KLL, DAA, SK, WC, YC, MAS, MM-D, DLS, JBA, SB, GPH; supervision/mentorship: MAS, KLL, DAA. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This work was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Disease (R01DK120518). Dr Lentine is supported by the Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation. Dr Schnitzler reports consulting fees from CareDx. Dr Axelrod reports honoraria from Sanofi and consulting fees from CareDx and Talaris. Dr Lentine reports speaker honoraria from Sanofi and consulting fees from CareDx. The remaining authors declare that they have no relevant financial interests. The data reported here have been supplied by the US Renal Data System. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government. Portions of these findings have been accepted for presentation at the 2021 American Transplant Congress virtual meeting. Received December 20, 2021. Evaluated by 3 external peer reviewers, with direct editorial input from the Statistical Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form March 13, 2022.
Funding Information:
This work was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Disease (R01DK120518). Dr Lentine is supported by the Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.
AB - Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.
KW - Aging
KW - Medicare
KW - economics
KW - fractures
KW - immunosuppression
KW - kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85131401257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131401257&partnerID=8YFLogxK
U2 - 10.1016/j.xkme.2022.100474
DO - 10.1016/j.xkme.2022.100474
M3 - Article
AN - SCOPUS:85131401257
VL - 4
JO - Kidney Medicine
JF - Kidney Medicine
SN - 2590-0595
IS - 6
M1 - 100474
ER -