Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward
Abstract
The pathophysiology of chronic kidney disease (CKD)-related mineral and bone disorder (CKD-MBD) extends far beyond simple mineral imbalances. Evolving from the traditional understanding of secondary hyperparathyroidism, the conceptual framework has recently been updated to recognize 2 distinct but overlapping clinical syndromes: CKD-associated osteoporosis, which encompasses the significantly increased fracture risk and microarchitectural deterioration in this population; and CKD-associated cardiovascular disease, which accounts for vascular and structural cardiac abnormalities, including medial vascular calcification. Unlike traditional osteoporosis, the 2 clinical syndromes emerge from intricate interactions between declining kidney function and dysregulated mineral metabolism. The early rise in fibroblast growth factor-23 (FGF-23) levels; progressive phosphate retention; diminished vitamin D activation; secondary hyperparathyroidism; and uremic toxin accumulation, particularly uric acid and indoxyl sulfate, orchestrate profound disruptions in osteocyte, osteoblast, and osteoclast function. The complex interaction amplifies in the dialysis population, where protein-energy wasting affects most patients; and intensifies following kidney transplantation because of glucocorticoid, immunosuppressive, and anticoagulant treatments. Consequently, fracture rates in patients with CKD exceed those of age-matched controls by >4-fold, with patients on dialysis therapy facing a ≤ 8-fold increased risk. Available diagnostic and predictive tools need to be improved to adequately identify at-risk patients. The usefulness of additional, more recent biomarkers such as FGF-23, a-Klotho, and various bone turnover parameters remains a matter of debate. Bone biopsy, considered as the diagnostic gold-standard, remains impractical in routine practice. Dual-energy X-ray absorptiometry (DXA) cannot provide information on the type of renal osteodystrophy. Moreover, it demonstrates limitations in the presence of severe vascular calcifications. Trabecular bone scores (TBS) emerge as potential progress in noninvasive bone imaging, showing modest superiority over traditional densitometry in predicting fracture risks among secondary osteoporosis populations, yet large clinical trials with long-term follow-up are required. Therapeutic management spans from parathyroidectomy to pharmacological interventions with bisphosphonates, denosumab, teriparatide, romosozumab, whereas agents such as burosumab remain investigational, with no published clinical trials in this population. However, therapeutic nihilism persists, with most high-risk patients not receiving bone-targeted therapy despite accumulating safety data. Transforming care demands abandoning therapeutic nihilism, embracing personalized risk stratification, and conducting trials in populations historically excluded from bone health research.
Related
- Complement system in kidney transplantation: from innate immune surveillance to a therapeutic and genetic engineering target
- Long-Term Kidney and Patient Survival after Deceased Donor Transplantation in Two Brothers with Alport Syndrome from the Same Donor
- A comparative transcriptomic framework across kidney organoid, assembloid, and transplantation models
- Kidney transplantation outcomes in older adults: the influence of comorbidity burden
- Application of endovascular stent graft in ABO-incompatible living donor kidney transplantation: a case report
BibTeX
@article{kanbay2026mineral,
title = {{Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward}},
author = {Mehmet Kanbay and Ozgur Aktas and Sidar Copur and Tilman B. Drueke and Ziad A. Massy},
journal = {Kidney International Reports},
year = {2026},
month = nov,
doi = {10.1016/j.ekir.2026.106662},
url = {https://hal.science/hal-05851605v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward
AU - Mehmet Kanbay
AU - Ozgur Aktas
AU - Sidar Copur
AU - Tilman B. Drueke
AU - Ziad A. Massy
PY - 2026
DA - 2026/11/04
JO - Kidney International Reports
DO - 10.1016/j.ekir.2026.106662
UR - https://hal.science/hal-05851605v1
AB - The pathophysiology of chronic kidney disease (CKD)-related mineral and bone disorder (CKD-MBD) extends far beyond simple mineral imbalances. Evolving from the traditional understanding of secondary hyperparathyroidism, the conceptual framework has recently been updated to recognize 2 distinct but overlapping clinical syndromes: CKD-associated osteoporosis, which encompasses the significantly increased fracture risk and microarchitectural deterioration in this population; and CKD-associated cardiovascular disease, which accounts for vascular and structural cardiac abnormalities, including medial vascular calcification. Unlike traditional osteoporosis, the 2 clinical syndromes emerge from intricate interactions between declining kidney function and dysregulated mineral metabolism. The early rise in fibroblast growth factor-23 (FGF-23) levels; progressive phosphate retention; diminished vitamin D activation; secondary hyperparathyroidism; and uremic toxin accumulation, particularly uric acid and indoxyl sulfate, orchestrate profound disruptions in osteocyte, osteoblast, and osteoclast function. The complex interaction amplifies in the dialysis population, where protein-energy wasting affects most patients; and intensifies following kidney transplantation because of glucocorticoid, immunosuppressive, and anticoagulant treatments. Consequently, fracture rates in patients with CKD exceed those of age-matched controls by >4-fold, with patients on dialysis therapy facing a ≤ 8-fold increased risk. Available diagnostic and predictive tools need to be improved to adequately identify at-risk patients. The usefulness of additional, more recent biomarkers such as FGF-23, a-Klotho, and various bone turnover parameters remains a matter of debate. Bone biopsy, considered as the diagnostic gold-standard, remains impractical in routine practice. Dual-energy X-ray absorptiometry (DXA) cannot provide information on the type of renal osteodystrophy. Moreover, it demonstrates limitations in the presence of severe vascular calcifications. Trabecular bone scores (TBS) emerge as potential progress in noninvasive bone imaging, showing modest superiority over traditional densitometry in predicting fracture risks among secondary osteoporosis populations, yet large clinical trials with long-term follow-up are required. Therapeutic management spans from parathyroidectomy to pharmacological interventions with bisphosphonates, denosumab, teriparatide, romosozumab, whereas agents such as burosumab remain investigational, with no published clinical trials in this population. However, therapeutic nihilism persists, with most high-risk patients not receiving bone-targeted therapy despite accumulating safety data. Transforming care demands abandoning therapeutic nihilism, embracing personalized risk stratification, and conducting trials in populations historically excluded from bone health research.
SN - 2468-0249
ER -