Hanne Skou Jørgensen1, Geert Behets2, Liesbeth Viaene3, Bert Bammens4, Kathleen Claes4, Bjorn Meijers4, Maarten Naesens4, Ben Sprangers4, Dirk Kuypers4, Etienne Cavalier5, Patrick D'Haese2, Pieter Evenepoel6. 1. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Kidney Diseases, Aarhus University Hospital, Aarhus, Denmark. 2. Laboratory of Pathophysiology, University of Antwerp, Wilrijk, Belgium. 3. Department of Nephrology, Az Groeninge, Kortrijk, Belgium. 4. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium. 5. Department of Clinical Chemistry, Université de Liège, Liège, Belgium. 6. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium. Electronic address: pieter.evenepoel@uzleuven.be.
Abstract
RATIONALE & OBJECTIVE: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. TESTS COMPARED: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). OUTCOME: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). RESULTS: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. LIMITATIONS: The single-center approach and heterogeneity of the study cohort are main limitations of this study. CONCLUSIONS: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease.
RATIONALE & OBJECTIVE: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. TESTS COMPARED: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). OUTCOME: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). RESULTS: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. LIMITATIONS: The single-center approach and heterogeneity of the study cohort are main limitations of this study. CONCLUSIONS: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease.
Keywords:
Alkaline phosphatase; bone histomorphometry; bone turnover markers; chronic kidney disease mineral and bone disorder (CKD-MBD); kidney transplantation; parathyroid hormone (PTH); sensitivity and specificity; tartrate-resistant acid phosphatase; transiliac bone biopsy
Authors: Mathias Haarhaus; Giuseppe Cianciolo; Simona Barbuto; Gaetano La Manna; Lorenzo Gasperoni; Giovanni Tripepi; Mario Plebani; Maria Fusaro; Per Magnusson Journal: Nutrients Date: 2022-05-19 Impact factor: 6.706