Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation

AbstractBone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18–70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.

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Changes in Bone Histomorphometry after Kidney Transplantation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.09950818 ◽

2019 ◽

Vol 14 (6) ◽

pp. 894-903 ◽

Cited By ~ 11

Author(s):

Satu Keronen ◽

Leena Martola ◽

Patrik Finne ◽

Inari S. Burton ◽

Heikki Kröger ◽

...

Keyword(s):

Kidney Transplantation ◽

Bone Turnover ◽

Kidney Transplant ◽

Bone Biopsy ◽

Bone Volume ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mineral Density ◽

Low Bone Turnover ◽

High Bone

Background and objectivesOver the past decade, the management of CKD–mineral and bone disorder has changed substantially, altering the pattern of bone disease in CKD. We aimed to evaluate the natural history of kidney bone disease in contemporary kidney transplant recipients and patients on dialysis.Design, settings, participants, & measurementsSixty one patients on dialysis who were referred to kidney transplantation participated in this prospective cohort study during November 2009 and December 2010. We performed baseline bone biopsies while the patients were on dialysis and repeated the procedure in 56 patients at 2 years after kidney transplantation or 2 years after baseline if transplantation was not performed. Measurements of mineral metabolism and bone turnover, as well as dual energy x-ray absorptiometry scans, were obtained concurrently.ResultsA total of 37 out of 56 participants received a kidney transplant, of which 27 underwent successful repeat bone biopsy. The proportion of patients with high bone turnover declined from 63% at baseline to 19% at 2 years after kidney transplantation, whereas the proportion of those with low bone turnover increased from 26% to 52%. Of 19 participants remaining on dialysis after 2 years, 13 underwent successful repeat biopsy. The proportion of patients remaining on dialysis with high bone turnover decreased from 69% to 31%, and low bone turnover increased from 8% to 38%. Abnormal bone mineralization increased in transplant recipients from 33% to 44%, but decreased in patients remaining on dialysis from 46% to 15%. Trabecular bone volume showed little change after transplantation, but low bone volume increased in patients remaining on dialysis. Bone mineral density did not correlate with histomorphometric findings.ConclusionsBone turnover decreased over time both in patients remaining on dialysis and in kidney transplant recipients. Bone mineral density and bone biomarkers were not associated with bone metabolism changes detected in bone biopsy specimens.

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FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab147.003 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Hanne Skou Jørgensen ◽

Geert Behets ◽

Patrick D'Haese ◽

Pieter Evenepoel

Keyword(s):

Kidney Transplantation ◽

Bone Turnover ◽

Kidney Transplant ◽

Renal Osteodystrophy ◽

Bone Disease ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Steroid Dose ◽

Bone Biopsies

Abstract Background and Aims Bone disease after kidney transplantation is an issue of growing concern, as prolonged graft survival and older age of recipients necessitate focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo disturbances of mineral metabolism all contribute to bone disease in kidney transplant recipients. The current pattern of renal osteodystrophy after kidney transplantation is not well characterized. This study reports histomorphometric findings of protocolled bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. Method Histomorphometric analysis of transiliac bone biopsies with prior tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical measurements included bioactive parathyroid hormone (PTH), total calcium, phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed rank tests were used to evaluate differences across categories and between groups, respectively. Stepwise multivariate linear regression was performed to identify key demographic and biochemical determinants of bone turnover (bone formation rate, BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr). Results Mean age was 57±11 years, 71% were men, and all were Caucasian. Mean eGFR was 49±16 (range 19 to 106) ml/min/1.73 m². Hyperparathyroidism (PTH > 1.5xUNL) was seen in 48%, hypercalcemia (>10.3 mg/dL) in 18%, hypophosphatemia (<2.3 mg/dl) in 12%, and vitamin D deficiency (<15 ng/mL) in 4% of patients. Categorization of bone turnover, mineralization, and volume is shown in Figure 1. Bone turnover was normal in the vast majority (71%). Patients with low turnover (26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low turnover; p=0.02). Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had higher levels of PTH (124 vs 53 ng/L, p<0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p<0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3 mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients with normal mineralization. Patients with low bone volume tended to be older (61 vs 56 years, p=0.07). Independent determinants of BFR were PTH (β=0.68, p<0.001) and cumulative steroid dose (β = -0.22, p=0.02). Determinants of Mlt were phosphate (β=-0.48, p=0.001) and cumulative steroid dose (β=0.18, p=0.004), and determinants of BAr were age (β=-0.15, p=0.002), and BMI (β=0.33, p=0.002). Conclusion Bone turnover is normal in the majority of kidney transplant recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism. Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone mineralization in kidney transplant recipients.

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FP768CHANGES IN BONE MINERAL DENSITY AND BONE TURNOVER MARKERS IN KIDNEY TRANSPLANT RECIPIENTS AND WAIT-LISTED CONTROLS; A PROSPECTIVE STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz106.fp768 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Hanne Skou Jørgensen ◽

Simon Winther ◽

Morten Bøttcher ◽

Ellen Hauge ◽

Lars Rejnmark ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Turnover ◽

Prospective Study ◽

Kidney Transplant ◽

Bone Turnover Markers ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mineral Density ◽

Turnover Markers ◽

A Prospective Study

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Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients

Kidney International ◽

10.1016/j.kint.2018.12.024 ◽

2019 ◽

Vol 95 (6) ◽

pp. 1461-1470 ◽

Cited By ~ 19

Author(s):

Pieter Evenepoel ◽

Kathleen Claes ◽

Bjorn Meijers ◽

Michaël R. Laurent ◽

Bert Bammens ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Turnover ◽

Kidney Transplant ◽

Bone Mineral ◽

Bone Turnover Markers ◽

De Novo ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mineral Density ◽

Turnover Markers

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The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1909 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2772-2780 ◽

Cited By ~ 45

Author(s):

Katherine Wesseling-Perry ◽

G. Chris Harkins ◽

He-jing Wang ◽

Robert Elashoff ◽

Barbara Gales ◽

...

Keyword(s):

Los Angeles ◽

Bone Turnover ◽

Healthy Volunteers ◽

Serum Calcium ◽

Bone Biopsy ◽

Dialysis Patients ◽

High Bone Turnover ◽

Dihydroxyvitamin D ◽

High Bone ◽

Adynamic Bone

Abstract Context: Factors contributing to PTH resistance in dialysis patients remain elusive. Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. Design: The study was a prospective, controlled assessment of response to PTH(1-34). Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center. Participants: Nineteen dialysis patients and 17 healthy volunteers were studied. Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg · h for 46 h. Bone biopsy was performed in all dialysis patients. Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. Results: Serum calcium levels rose in healthy volunteers (9.2 ± 0.1 to 11.9 ± 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 ± 0.3 to 10.7 ± 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 ± 0.1 to 3.5 ± 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 ± 0.4 to 8.0 ± 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.

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Effects of Paricalcitol On Bone Turnover in Kidney Transplant Recipients.

Transplantation Journal ◽

10.1097/00007890-201407151-03012 ◽

2014 ◽

Vol 98 ◽

pp. 882 ◽

Cited By ~ 1

Author(s):

H. Amer ◽

M. Griffin ◽

Z. Ryan ◽

W. Park ◽

W. Kremers ◽

...

Keyword(s):

Bone Turnover ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Elevation of serum alkaline phosphatase (ALP) level in postmenopausal women is caused by high bone turnover

Aging Clinical and Experimental Research ◽

10.1007/s40520-014-0296-x ◽

2014 ◽

Vol 27 (4) ◽

pp. 413-418 ◽

Cited By ~ 57

Author(s):

Keijiro Mukaiyama ◽

Mikio Kamimura ◽

Shigeharu Uchiyama ◽

Shota Ikegami ◽

Yukio Nakamura ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Postmenopausal Women ◽

Serum Alkaline Phosphatase ◽

High Bone Turnover ◽

High Bone

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Bone Turnover Markers and Fracture Risk in African American Kidney Transplant Recipients with Hypovitaminosis D and Hyperparthyroidism

Journal of Clinical Densitometry ◽

10.1016/j.jocd.2010.01.045 ◽

2010 ◽

Vol 13 (1) ◽

pp. 115-116

Author(s):

Mariana Markell ◽

Sima Terebelo

Keyword(s):

African American ◽

Bone Turnover ◽

Fracture Risk ◽

Kidney Transplant ◽

Bone Turnover Markers ◽

Hypovitaminosis D ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Turnover Markers

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FC 076DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN RENAL OSTEODYSTROPHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab123.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Hanne Skou Jørgensen ◽

Geert Behets ◽

Etienne Cavalier ◽

Patrick D'Haese ◽

Pieter Evenepoel

Keyword(s):

Bone Turnover ◽

Kidney Transplant ◽

Renal Osteodystrophy ◽

Type I Collagen ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Predictive Values ◽

Bone Biopsies

Abstract Background and Aims A transiliac bone biopsy is the gold standard for diagnosing renal osteodystrophy, but is not recommended as part of routine clinical workup due to its invasive nature. Suitable non-invasive alternatives have yet to be established. The aim of this study was to investigate the diagnostic accuracy novel biochemical markers of bone remodeling compared to that of biointact parathyroid hormone (PTH) for bone turnover as evaluated by histomorphometry. Method Protocolled bone biopsies were performed in end-stage kidney disease patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84) PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). Optimal diagnostic cutoffs were established in an exploration cohort (n=100), and subsequently validated in a separate subset of patients (n=99). Results Mean age was 55±13 years, two-thirds were men (67%), and 23% had diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m². Bone turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All biomarkers differed significantly across categories of bone turnover (p < 0.001). The AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87, 0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63, 0.78), which was significantly lower than the values for BsAP, Intact P1NP, and TRAP5b (0.79, 0.83, and 0.79, respectively; p < 0.05, all). Calculated optimal diagnostic cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the validation cohort revealed high negative predictive values for both high (92 - 96%) and low (82 - 90%) bone turnover. Positive predictive values were consistently low. Conclusion The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows inferior performance, particularly in kidney transplant recipients.

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