Natural History of Bone Disease following Kidney Transplantation

Abstract

Background: Knowledge of the impact of kidney transplantation on bone is limited and fragmentary. The aim of this study was to characterize the evolution of bone disease in the first post-transplant year. Methods: We performed a prospective, observational cohort study in patients referred for kidney transplantation under a steroid-sparing immunosuppressive protocol. Bone phenotyping was done prior to, or at the time of, kidney transplantation, and repeated at 12 months post-transplant. The phenotyping included bone histomorphometry, bone densitometry by dual-energy x-ray absorptiometry, and biochemical parameters of bone and mineral metabolism. Results: Paired data were obtained for 97 patients (median age 55 years, 72% male, 21% diabetics). Bone turnover remained normal or improved in the majority (65%). Bone histomorphometry revealed decreases in bone resorption (eroded perimeter 4.6% to 2.3%, p<0.001) and disordered bone formation (fibrosis 27% pre-vs 2% post-transplant, p<0.001). While bone mineralization was normal in all but 1 patient pre-transplant, delayed mineralization was seen in 15% of patients at 1 year post-transplant. Hypophosphatemia was associated with deterioration in histomorphometric parameters of bone mineralization. Changes in bone mineral density were highly variable, ranging from -18 to +17% per year. Cumulative steroid dose was related to bone loss at the hip, while resolution of hyperparathyroidism was related to bone gain at both spine and hip. Conclusions: Changes in bone turnover, mineralization, and volume post-transplant are related to both steroid exposure and ongoing disturbances of mineral metabolism. Optimal control of mineral metabolism may be key to improving bone quality in kidney transplant recipients.

Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects

“…As underlined in two consecutive studies by Evenepoel et al and Jorgensen et al, the GC cumulative dosage reduction of the latest immunosuppressive protocols had a great beneficial impact on bone health, favouring bone mineralization and reducing bone loss. Steroid minimisation protocols were associated with stable MBD after RTx, with significantly present bone loss only in the distal radius area (37,38,48). However, it must be remembered that even low doses of GC hamper bone metabolism, reducing bone formation and mineralization, and independently increasing the fracture risk (34,49).…”

“…The histomorphometric study performed in this cohort showed an overall decrease in skeletal remodelling and bone turnover after RTx. Nevertheless, during the first year of RTx disorders of bone formation linked to HPT, such as excessive bone resorption and marrow fibrosis, were markedly decreased on histologic samples ( 37 ). Furthermore, in patients for whom it was possible to obtain dynamic histomorphometric data, similar findings were obtained with no significant changes in bone volume.…”

“…Cumulative steroid dosage was directly correlated with slower bone turnover and mineralization. Even if the wider use of steroid minimisation protocols has reduced the impact of GC on bone quality and density after-RTx, it appears that the negative effect of GC is exerted even with low exposure, with the most evident consequences on hip-MBD ( 37 ). Bone mineralization showed to be greatly influenced also by phosphate levels.…”

“…Bone mineralization showed to be greatly influenced also by phosphate levels. The severity and the duration of hypophosphatemia negatively affected bone mineralization ( 37 , 39 ). Since several factors that influence bone health, in a positive and a negative manner, come into play in the post-RTx period, it is readably understandable why there has been such great variability in the findings regarding post-RTx BMD.…”

“…In this cohort of patients, DEXA findings were suggestive for substantial stability of MBD, especially in the axial skeleton. The main changes, found in a minority of the cohort, are a decrease in MBD at the distal radius and an increase in bone mass at the hip ( 37 ). These findings are in accordance with histomorphometric and biochemical findings, thus, corroborating the diagnostic and prognostic value of DEXA in the follow-up of RTx-BMD.…”