Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices

Maria Fusaro; Simona Barbuto; Maurizio Gallieni; Althea Cossettini; Giulia Vanessa Re Sartò; Laura Cosmai; Giuseppe Cianciolo; Gaetano La Manna; Thomas Nickolas; Serge Ferrari; Jordi Bover; Mathias Haarhaus; Carmela Marino; Maria Cristina Mereu; Maura Ravera; Mario Plebani; Martina Zaninotto; Mario Cozzolino; Stefano Bianchi; Piergiorgio Messa; Mariacristina Gregorini; Lorenzo Gasperoni; Caterina Agosto; Andrea Aghi; Giovanni Tripepi

doi:10.1093/ckj/sfad290

Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices

Clin Kidney J. 2023 Nov 29;17(1):sfad290. doi: 10.1093/ckj/sfad290. eCollection 2024 Jan.

Authors

Maria Fusaro^{1

2}, Simona Barbuto³, Maurizio Gallieni^{4

5

6}, Althea Cossettini⁵, Giulia Vanessa Re Sartò⁵, Laura Cosmai⁶, Giuseppe Cianciolo³, Gaetano La Manna³, Thomas Nickolas⁷, Serge Ferrari⁸, Jordi Bover⁹, Mathias Haarhaus¹⁰, Carmela Marino¹¹, Maria Cristina Mereu¹², Maura Ravera¹³, Mario Plebani¹⁴, Martina Zaninotto¹⁴, Mario Cozzolino¹⁵, Stefano Bianchi¹⁶, Piergiorgio Messa¹⁷, Mariacristina Gregorini¹⁸, Lorenzo Gasperoni¹⁹, Caterina Agosto²⁰, Andrea Aghi²¹, Giovanni Tripepi¹¹

Affiliations

¹ National Research Council (CNR), Institute of Clinical Physiology (IFC), Pisa, Italy.
² Department of Medicine, University of Padova, Padova, Italy.
³ Nephrology, Dialysis and Renal Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Bologna, Italy.
⁴ Department of Biomedical and Clinical Sciences 'Luigi Sacco', Università di Milano, Milano, Italy.
⁵ Post-Graduate School of Specialization in Nephrology, University of Milano, Milano, Italy.
⁶ Division of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Fatebenefratelli Hospital, Milan, Italy.
⁷ Department of Medicine, Division of Nephrology, Columbia University, New York, NY, USA.
⁸ Service des Maladies Osseuses, Département de Médecine, HUG, Geneva, Switzerland.
⁹ Servicio de Nefrología, Hospital Universitario Germans Trias i Pujol, Badalona (Barcelona), Spain.
¹⁰ Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
¹¹ National Research Council (CNR), Institute of Clinical Physiology (IFC), Reggio Calabria, Italy.
¹² Independent Researcher, Cagliari, Italy.
¹³ Nephrology, Dialysis, and Transplantation, University of Genoa and Policlinico San Martino, 16132 Genoa, Italy.
¹⁴ Laboratory Medicine Unit, Department of Medicine, University of Padua, Padua, Italy.
¹⁵ Department of Health Sciences, Renal Division, University of Milan, ASST Santi Paolo e Carlo, Milan, Italy.
¹⁶ Department of Internal Medicine, Nephrology and Dialysis Complex Operative Unit, Livorno, Italy.
¹⁷ Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁸ SC Nefrologia e Dialisi AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy.
¹⁹ Nephrology and Dialysis Unit, Infermi Hospital, AUSL Romagna, Rimini, Italy.
²⁰ Pediatric Pain and Palliative Care Service, Department of Women's and Children's Health, Padua University Hospital, Padua, Italy.
²¹ Independent Researcher, Padua, Italy.

Abstract

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice.

Methods: A national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice.

Results: One hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH)₂D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range.

Conclusion: Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.

Keywords: CKD-MBD; bone biomarkers; bone fractures; bone turnover markers; vascular calcifications.