Abstract
Amaç: Renal osteodistrofi, osteoporoz, kemik kırıkları ve avasküler nekroz (AVN), böbrek nakli alıcılarında (BNA) transplantasyon sonrası dönemde yaygın komplikasyonlardır. Kaydedilen önemli ilerlemelere rağmen, AVN böbrek nakli (BN) sonrası hala ciddi ve yıkıcı bir komplikasyon olmaya devam etmektedir.
Gereç ve Yöntem: Çalışmaya, transplantasyon ünitemizde BN yapılan ve en az bir yıl düzenli takip edilen tüm hastalar (n=343) dahil edildi. Semptomatik AVN vakaları röntgen, radyoizotop kemik taraması veya manyetik rezonans görüntüleme ile teşhis edildi. BNA’ların temel özellikleri, laboratuvar sonuçları ve immünsüpresif tedavileri değerlendirildi.
Bulgular: BNA’larda AVN sıklığı %7,9 olup, medyan teşhis süresi 15,2 (10,2-34,9) ay olarak belirlendi. AVN gelişen BNA’larda, son dönem böbrek hastalığının en yaygın nedeni glomerulonefrit (GN) idi (%52’ye karşı %20, p<0,001) ve takip sürecinde daha fazla rejeksiyon epizodu görüldü (%33’e karşı %15, p=0,01). Tek değişkenli analizde GN [olasılık oranı (OR): 4,325; %95 güven aralığı (GA), 1,936-9,661], nakil sonrası ilk yıldaki kümülatif steroid dozu (OR: 1,001; %95 GA, 1,000-1,002) ve rejeksiyon epizodları (OR: 2,792; %95 GA, 1,185-6,578) AVN için olası risk faktörleri olarak saptandı. Çok değişkenli analizde ise GN, AVN gelişimi için bağımsız bir risk faktörü olarak belirlendi (OR: 4,373; %95 GA, 1,935-9,880;
Keywords
Avascular necrosis glomerulonephritis mineral bone disease renal transplantation steroid therapy
Project Number
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References
- 1. Abecassis M, Bartlett ST, Collins AJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol. 2008;3:471-480.
- 2. Teh JW, Mac Gearailt C, Lappin DWP. Post-Transplant bone disease in kidney transplant recipients: diagnosis and management. Int J Mol Sci. 2024;25:1859
- 3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney diseasemineral and bone disorder (CKD-MBD). Kidney Int Suppl (2011). 2017;7:159. Erratum in: Kidney Int Suppl (2011). 2017;7:e1.
- 4. Nehme D, Rondeau E, Paillard F, et al. Aseptic necrosis of bone following renal transplantation: relation with hyperparathyroidism. Nephrol Dial Transplant. 1989;4:123-128.
- 5. Takao M, Sakai T, Nishii T, Yoshikawa H, Takahara S, Sugano N. Incidence and predictors of osteonecrosis among cyclosporin- or tacrolimus-treated renal allograft recipients. Rheumatol Int. 2011;31:165-70.
- 6. Schachtner T, Otto NM, Reinke P. Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study. Nephrol Dial Transplant. 2018;33:2060-2066.
- 7. Felten R, Perrin P, Caillard S, Moulin B, Javier RM. Avascular osteonecrosis in kidney transplant recipients: Risk factors in a recent cohort study and evaluation of the role of secondary hyperparathyroidism. PLoS One. 2019;14:e0212931.
- 8. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112:352-364.
- 9. Ferrari P, Schroeder V, Anderson S, et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroidtreated renal allograft recipients. Transplantation. 2002;74:1147-1152.
- 10. Lai SW, Lin CL, Liao KF. Real-world database examining the association between avascular necrosis of the femoral head and diabetes in Taiwan. Diabetes Care. 2019;42:39-43.
- 11. Tsai HL, Chang JW, Lu JH, Liu CS. Epidemiology and risk factors associated with avascular necrosis in patients with autoimmune diseases: a nationwide study. Korean J Intern Med. 2022;37:864-876.
- 12. Jeong HJ. Diagnosis of renal transplant rejection: Banff classification and beyond. Kidney Res Clin Pract. 2020;39:17-31.
- 13. Hedri H, Cherif M, Zouaghi K, et al. Avascular osteonecrosis after renal transplantation. Transplant Proc. 2007;39:1036-1038.
- 14. Metselaar HJ, van Steenberge EJ, Bijnen AB, Jeekel JJ, van Linge B, Weimar W. Incidence of osteonecrosis after renal transplantation. Acta Orthop Scand. 1985;56:413-415.
- 15. Paydas S, Balal M, Demir E, Sertdemir Y, Erken U. Avascular osteonecrosis and accompanying anemia, leucocytosis, and decreased bone mineral density in renal transplant recipients. Transplant Proc. 2011;43:863-866.
- 16. Kim CH, Lim EJ, Lee J. Clinical outcomes following primary hip replacement arthroplasties in patients with solid organ transplantation: a systematic review and meta-analysis. Hip Pelvis. 2022;34:127-139.
- 17. Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine. 2012;41:183-190.
- 18. Higuchi Y, Tomosugi T, Futamura K, et al. Incidence and risk factors for osteonecrosis of the hip in renal transplant patients: a prospective singlecentre study. Int Orthop. 2020;44:1927-1933.
- 19. Ekmekci Y, Keven K, Akar N, et al. Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients. Nephrol Dial Transplant. 2006;21:3555-3558.
- 20. Khwaja K, Asolati M, Harmon J, et al. Outcome at 3 years with a prednisonefree maintenance regimen: a single-center experience with 349 kidney transplant recipients. Am J Transplant. 2004;4:980-987.
- 21. Khairallah P, Nickolas TL. Bone and mineral disease in kidney transplant recipients. Clin J Am Soc Nephrol. 2022;17:121-130.
- 22. Zhao J, He W, Zheng H, Zhang R, Yang H. Bone regeneration and angiogenesis by co-transplantation of angiotensin ii-pretreated mesenchymal stem cells and endothelial cells in early steroid-induced osteonecrosis of the femoral head. Cell Transplant. 2022;31:9636897221086965.
- 23. Shi RZ, Wang JC, Huang SH, Wang XJ, Li QP. Angiotensin II induces vascular endothelial growth factor synthesis in mesenchymal stem cells. Exp Cell Res. 2009;315:10-15.
- 24. Wang P, Shao W, Wang Y, Wang B, Lv X, Feng Y. Angiogenesis of avascular necrosis of the femoral head: a classic treatment strategy. Biomedicines. 2024;12:2577.
- 25. Yu TM, Chen YH, Lan JL, et al. Renal outcome and evolution of disease activity in Chinese lupus patients after renal transplantation. Lupus. 2008;17:687-694.
Abstract
Objectives: Renal osteodystrophy, osteoporosis, bone fractures, and avascular necrosis (AVN) are prevalent complications observed in the posttransplant period among kidney transplant recipients (KTRs). Despite notable advancements, AVN remains a significant and devastating complication following kidney transplantation (KT).
Materials and Methods: The study included all patients who underwent KT at our transplantation unit and had at least one year of routine followup (n=343). Cases of symptomatic AVN were diagnosed by X-radiation, radioisotope bone scan, or magnetic resonance imaging. We evaluated the baseline characteristics, laboratories, and immunosuppressive treatments of KTRs.
Results: The frequency of AVN in our KTRs was 7.9% during the follow-up period, with a median diagnosis time of 15.2 (10.2-34.9) months. In KTRs with AVN, the leading cause of end-stage renal disease was glomerulonephritis (GN) (52% vs. 20%, p<0.001), and more rejection episodes occurred at follow-up (33% vs. 15%, p=0.01). In univariate analysis, GN [odds ratio (OR): 4.325, 95% confidence interval (CI), 1.936-9.661], cumulative steroid dosage at the post-transplant first year (OR: 1.001, 95% CI, 1.000-1.002), and rejection episodes (OR: 2.792, 95% CI, 1.185-6.578) detected as possible risk factors for AVN. Upon multivariate analysis, GN was identified as an independent risk factor for the development of AVN (OR: 4.373, 95% CI, 1.935-9.880, p<0.001).
Conclusion: Our study found GN to be associated with an increased risk of AVN. A higher prevalence of AVN may attributed to long-term pretransplant steroid therapy in this group. In KTRs with a history of GN, greater awareness should be paid to cumulative steroid dosages, and early discontinuation of steroids may be considered.
Keywords
Avascular necrosis glomerulonephritis mineral bone disease renal transplantation steroid therapy
Ethical Statement
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Supporting Institution
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Project Number
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Thanks
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References
- 1. Abecassis M, Bartlett ST, Collins AJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol. 2008;3:471-480.
- 2. Teh JW, Mac Gearailt C, Lappin DWP. Post-Transplant bone disease in kidney transplant recipients: diagnosis and management. Int J Mol Sci. 2024;25:1859
- 3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney diseasemineral and bone disorder (CKD-MBD). Kidney Int Suppl (2011). 2017;7:159. Erratum in: Kidney Int Suppl (2011). 2017;7:e1.
- 4. Nehme D, Rondeau E, Paillard F, et al. Aseptic necrosis of bone following renal transplantation: relation with hyperparathyroidism. Nephrol Dial Transplant. 1989;4:123-128.
- 5. Takao M, Sakai T, Nishii T, Yoshikawa H, Takahara S, Sugano N. Incidence and predictors of osteonecrosis among cyclosporin- or tacrolimus-treated renal allograft recipients. Rheumatol Int. 2011;31:165-70.
- 6. Schachtner T, Otto NM, Reinke P. Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study. Nephrol Dial Transplant. 2018;33:2060-2066.
- 7. Felten R, Perrin P, Caillard S, Moulin B, Javier RM. Avascular osteonecrosis in kidney transplant recipients: Risk factors in a recent cohort study and evaluation of the role of secondary hyperparathyroidism. PLoS One. 2019;14:e0212931.
- 8. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112:352-364.
- 9. Ferrari P, Schroeder V, Anderson S, et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroidtreated renal allograft recipients. Transplantation. 2002;74:1147-1152.
- 10. Lai SW, Lin CL, Liao KF. Real-world database examining the association between avascular necrosis of the femoral head and diabetes in Taiwan. Diabetes Care. 2019;42:39-43.
- 11. Tsai HL, Chang JW, Lu JH, Liu CS. Epidemiology and risk factors associated with avascular necrosis in patients with autoimmune diseases: a nationwide study. Korean J Intern Med. 2022;37:864-876.
- 12. Jeong HJ. Diagnosis of renal transplant rejection: Banff classification and beyond. Kidney Res Clin Pract. 2020;39:17-31.
- 13. Hedri H, Cherif M, Zouaghi K, et al. Avascular osteonecrosis after renal transplantation. Transplant Proc. 2007;39:1036-1038.
- 14. Metselaar HJ, van Steenberge EJ, Bijnen AB, Jeekel JJ, van Linge B, Weimar W. Incidence of osteonecrosis after renal transplantation. Acta Orthop Scand. 1985;56:413-415.
- 15. Paydas S, Balal M, Demir E, Sertdemir Y, Erken U. Avascular osteonecrosis and accompanying anemia, leucocytosis, and decreased bone mineral density in renal transplant recipients. Transplant Proc. 2011;43:863-866.
- 16. Kim CH, Lim EJ, Lee J. Clinical outcomes following primary hip replacement arthroplasties in patients with solid organ transplantation: a systematic review and meta-analysis. Hip Pelvis. 2022;34:127-139.
- 17. Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine. 2012;41:183-190.
- 18. Higuchi Y, Tomosugi T, Futamura K, et al. Incidence and risk factors for osteonecrosis of the hip in renal transplant patients: a prospective singlecentre study. Int Orthop. 2020;44:1927-1933.
- 19. Ekmekci Y, Keven K, Akar N, et al. Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients. Nephrol Dial Transplant. 2006;21:3555-3558.
- 20. Khwaja K, Asolati M, Harmon J, et al. Outcome at 3 years with a prednisonefree maintenance regimen: a single-center experience with 349 kidney transplant recipients. Am J Transplant. 2004;4:980-987.
- 21. Khairallah P, Nickolas TL. Bone and mineral disease in kidney transplant recipients. Clin J Am Soc Nephrol. 2022;17:121-130.
- 22. Zhao J, He W, Zheng H, Zhang R, Yang H. Bone regeneration and angiogenesis by co-transplantation of angiotensin ii-pretreated mesenchymal stem cells and endothelial cells in early steroid-induced osteonecrosis of the femoral head. Cell Transplant. 2022;31:9636897221086965.
- 23. Shi RZ, Wang JC, Huang SH, Wang XJ, Li QP. Angiotensin II induces vascular endothelial growth factor synthesis in mesenchymal stem cells. Exp Cell Res. 2009;315:10-15.
- 24. Wang P, Shao W, Wang Y, Wang B, Lv X, Feng Y. Angiogenesis of avascular necrosis of the femoral head: a classic treatment strategy. Biomedicines. 2024;12:2577.
- 25. Yu TM, Chen YH, Lan JL, et al. Renal outcome and evolution of disease activity in Chinese lupus patients after renal transplantation. Lupus. 2008;17:687-694.
Details
| Primary Language | English |
|---|---|
| Subjects | Nefroloji |
| Journal Section | Articles |
| Authors | |
| Project Number | - |
| Publication Date | July 1, 2025 |
| Submission Date | January 28, 2025 |
| Acceptance Date | March 7, 2025 |
| Published in Issue | Year 2025 Volume: 79 Issue: 2 |