In 2017, Kidney Disease: Improving Global Outcomes (KDIGO) published a Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Since then, new lines of evidence have been published related to evaluating disordered mineral metabolism and bone quality and turnover, identifying and inhibiting vascular calcification, targeting vitamin D levels, and regulating parathyroid hormone. For an in-depth consideration of the new insights, in October 2023, KDIGO held a Controversies Conference on CKD-MBD: Progress and Knowledge Gaps Toward Personalizing Care. Participants concluded that the recommendations in the 2017 CKD-MBD guideline remained largely consistent with the available evidence. However, the framework of the 2017 Guideline, with 3 major sections-biochemical abnormalities in mineral metabolism; bone disease; and vascular calcification-may no longer best reflect currently available evidence related to diagnosis and treatment. Instead, future guideline efforts could consider mineral homeostasis and deranged endocrine systems in adults within a context of 2 clinical syndromes: CKD-associated osteoporosis, encompassing increased fracture risk in patients with CKD; and CKD-associated cardiovascular disease, including vascular calcification and structural abnormalities, such as valvular calcification and left ventricular hypertrophy. Participants emphasized that the complexity of bone and cardiovascular manifestations of CKD-MBD necessitates personalized approaches to management.

Purpose The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. Methods Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. Results Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. Conclusion We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800–1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations. In a collaboration between the European Renal Osteodystrophy initiative of the European Renal Association (ERA) and the European Society for Paediatric Nephrology (ESPN), an expert panel performed an extensive literature review and formulated clinical practice points on vitamin D supplementation in children and adults with CKD and after kidney transplantation. These were reviewed by a Delphi panel of members from relevant working groups of the ERA and ESPN. Key clinical practice points include recommendations to monitor for, and correct, vitamin D deficiency in children and adults with CKD and after kidney transplantation, targeting 25-hydroxyvitamin D levels >75 nmol/l (>30 ng/ml). Although vitamin D supplementation appears well-tolerated and safe, it is recommended to avoid mega-doses (≥100 000 IU) and very high levels of 25 hydroxyvitamin D (>150–200 nmol/l, or 60–80 ng/ml) to reduce the risk of toxicity. Future clinical trials should investigate the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency across different stages of CKD.