FC 076DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN RENAL OSTEODYSTROPHY

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.

FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

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.

TO005OPERATIONAL TOLERANCE IN KIDNEY TRANSPLANT RECIPIENTS: TOMOGRAM TRANSCRIPTOMIC STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ondrej Viklicky ◽  
Jiri Klema ◽  
Petra Mrazova ◽  
Daniel Abramowicz ◽  
Marc Abramowicz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Kidney Transplant ◽  
Type I Interferon ◽  
Gene Annotation ◽  
Interferon Γ ◽  
Type I ◽  
Transplant Recipients ◽  
Interferon Signaling ◽  
Kidney Transplant Recipients ◽  
Operational Tolerance

Abstract Background and Aims TOMOGRAM, multicenter study founded by DESCARTES ERA/EDTA WG, aims to identify transcriptomic and genomic signatures of operational tolerance (OT) in recently identified cohort of OT kidney transplant recipients. Method RNA sequencing of peripheral blood was evaluated in 15 OT patients recently identified by TOMOGRAM consortium in 8 European countries, 23 stable patients (≥ 15 years on immunosuppression, STA), 14 CABMR patients (≥ 1 year, CR), 14 non-transplant CNI-treated patients and 14 healthy controls (HC). Differential expression was performed using DESEq2 and gene annotation analysis using Enrichr. Besides immunosuppression unadjusted model, robust negative-binomial regression model was created to adjust for immunosuppression intake. The models was trained on homogeneous group of STA patients. Results Using model unadjusted for immunosuppression, no differences in transcriptomic profiles between OT, STA and HC groups were identified. Nine transcripts were upregulated and 2 downregulated in OT compared CR group. The number of deregulated transcripts substantially increased when the model was adjusted for immunosuppression. Gene annotation analysis of top ranked deregulated 1109 transcripts (FC>2, adjusted p value <0.0001) showed deregulation of biological processes related to interferon-γ-mediated signaling pathway (p=1.4*10-5), response to cytokine (p=1.5*10-5), type I interferon signaling pathway (p=0.00036), regulation of I-kappaB kinase/NF-kappaB signaling (p=0.0021), cytokine-mediated signaling pathway (p=0.019) and neutrophil mediated immunity (p=0.033). While interferon-γ-mediated and type I interferon signaling were related to transcripts increased in CR, neutrophils associated transcripts were increased in OT. Analysis of cell types transcripts showed enrichment of CD19 B cells (p=1.6*10-9) in CR, while CD56NK cells (p=2.5*10-11) and CD8 T cells (p=1.6*10-11) transcripts predominated in OT. To reveal probability of operational tolerance inside STA group, 13 transcripts able to discriminate OT and CR cohorts with high AUC (>0.89) were used in PCA analysis (ADGRG3, ATG2A, GDPD5, IL16, MX2, SLA2, PRKD2, SLIRP, GNLY, SRCAP, ARGHAP9, IGHM, CD5). The high probability of OT signature was found in a single STA patient. Conclusion Contrary to previous reports which pointed out towards naïve B cell signatures, unique OT patients exhibit other specific immunosuppression-independent transcriptomic profiles.

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

2019 ◽  
Vol 95 (6) ◽  
pp. 1461-1470 ◽  
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

Effects of Paricalcitol On Bone Turnover in Kidney Transplant Recipients.

2014 ◽  
Vol 98 ◽  
pp. 882 ◽  
Author(s):  
H. Amer ◽  
M. Griffin ◽  
Z. Ryan ◽  
W. Park ◽  
W. Kremers ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Patients with cirrhosis have elevated bone turnover but normal hepatic production of osteoprotegerin

2021 ◽  
Author(s):  
Niklas Rye Jørgensen ◽  
Sarah Seberg Diemar ◽  
Gitte Lund Christensen ◽  
Nina Kimer ◽  
Karen Vagner Danielsen ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Alcoholic Cirrhosis ◽  
University Hospital ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Metabolism Markers ◽  
Cirrhotic Patients ◽  
Control Study

Abstract Context Severe osteodystrophy is common in patients with liver dysfunction. Markers of bone metabolism may help in early diagnosis of osteodystrophy and in understanding underlying pathophysiological mechanisms. Objective To elucidate changes in bone metabolism associated with cirrhosis and to determine the route of elimination for the markers. Design Case-control study. Setting Public university hospital. Patients Fifty-nine patients with cirrhosis (47 alcoholic and 12 non-alcoholic cirrhosis), 20 controls. Interventions Participants underwent catheterization of the femoral artery, and the hepatic, kidney and femoral veins with collection of blood from all four sites. Main outcome measures Regional arterio-venous differences in concentrations of bone metabolism markers were determined: procollagen of type I collagen propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OC), tartrate-resistant acid phosphatase isoform 5b (TRAcP5b), osteoprotegerin (OPG), and sclerostin and correlated with degree of disease (Child-Pugh Classification). Results PINP concentration was higher (median: 87.9 µg/L) in patients with cirrhosis than in controls (52.6 µg/L)(p=0.001), while hepatic extraction was lower 4.3% vs. 14.5% (p<0.001). Both CTX and TRAcP5b were higher in cirrhotic patients (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L)(p<0.001 and p<0.0001). Hepatic sclerostin extraction was lower in cirrhotics (14.6%) than in controls (28.7%)(p<0.0001). In both groups OPG showed a hepatic release rate (production) of 6%. Conclusions Patients with cirrhosis have increased bone resorption, but unaltered bone formation. Sclerostin is eliminated through the liver while OPG is produced in the liver. Bone markers may prove useful in evaluating bone turnover in cirrhosis patients.

scholarly journals Associations between Serum Leptin Level and Bone Turnover in Kidney Transplant Recipients

2010 ◽  
Vol 5 (12) ◽  
pp. 2297-2304 ◽  
Author(s):  
Csaba P. Kovesdy ◽  
Miklos Z. Molnar ◽  
Maria E. Czira ◽  
Anna Rudas ◽  
Akos Ujszaszi ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Serum Leptin

scholarly journals Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation

2021 ◽  
Author(s):  
Satu M. Keronen ◽  
Leena A. L. Martola ◽  
Patrik Finne ◽  
Inari S. Burton ◽  
Xiaoyu F. Tong ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Bone Biopsy ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Bone Biomarkers ◽  
High Turnover ◽  
High Bone Turnover ◽  
High Bone

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.

MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Bone Turnover ◽  
Diagnostic Accuracy ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
Bone Formation Rate ◽  
Suitable Alternative ◽  
Predictive Values ◽  
Bone Biopsies ◽  
Low Bone Turnover ◽  
Tetracycline Labeling

Abstract Background and Aims A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover. Method Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100). Results All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1. Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%. Conclusion Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.

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