Natural History of Bone Disease following Kidney Transplantation

Abstract

Background: Knowledge of the effect 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 before, 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% of patients had diabetes). Bone turnover remained normal or improved in the majority of patients (65%). Bone histomorphometry revealed decreases in bone resorption (eroded perimeter, mean 4.6% pre- to 2.3% post-transplant; P<0.001) and disordered bone formation (fibrosis, 27% pre- versus 2% post-transplant; P<0.001). Whereas bone mineralization was normal in all but one patient pretransplant, 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, whereas 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 both to steroid exposure and ongoing disturbances of mineral metabolism. Optimal control of mineral metabolism may be key to improving bone quality in kidney transplant recipients.

Clinical trial registry name and registration number: Evolution of Bone Histomorphometry and Vascular Calcification Before and After Renal Transplantation, NCT01886950.

Keywords: bone diseases; clinical nephrology; hyperparathyroidism; kidney transplantation; mineral metabolism.

Graphical abstract

Figure 1.

Normal and abnormal bone histology in the context of CKD. (A) Normal bone. (B) Low bone turnover with very few bone cells and bone surfaces without osteoid. (C) High bone turnover with large numbers of osteoblasts (white arrows) and osteoclasts (yellow arrows), zones of bone erosion and fibrosis (green arrow), generous amounts of osteoid (orange). (D) Delayed mineralization with broad osteoid seams (orange), disproportionate to the bone turnover. (E) Low bone volume with reduced amounts of mineralized tissue (blue). (F) High bone volume with generous amounts of well-connected trabecular bone (blue).

Figure 2.

Evolution of mineral metabolism in the first post-transplant year. Biointact PTH, total calcium, phosphate, calcidiol, and bicarbonate at baseline, lowest registered value (nadir), time-averaged concentration (TAC) months 0–3, TAC months 3–12, and measurements at 12 months post-transplant, as violin plots with median and IQR (dotted lines).

Figure 3.

Evolution of TMV classification in the first post-transplant year. Changes in bone TMV by bone histomorphometry from baseline to 1 year after kidney transplantation.

Figure 4.

Bone turnover declines and bone mineralization slows in the first post-transplant year. Changes in bone formation rate by total tissue volume (BFR/TV) and mineralization lag time (Mlt) in the subset patients with TC-labeled bone biopsies taken median 261 (IQR, 139–669) days before transplantation and repeated at 12 months post-transplant. P by Wilcoxon matched-pairs signed-rank test.

Figure 5.

Subsets of patients experience bone loss or bone gain in the first post-transplant year. Annualized change in BMD by DXA at lumbar spine (%LS), total hip (%TH), femoral neck (%FN), distal third radius (%13R), and ultradistal radius (%UDR); dashed lines represent least significant change (±5%).