Diagnostic utility of FGF-23 in mineral bone disorder during chronic kidney disease

Our data confirm that intact fibroblast growth factor 23 (iFGF-23) concentration is increased in patients with chronic kidney disease (CKD) and that it increases with disease progression (stages I-V). Therefore, iFGF-23 could be considered an early biomarker in the course of chronic kidney disease-mineral bone disorder (CKD-MBD), which has several aspects that make it potentially useful in clinical practice. The availability of an automated method for iFGF-23 assay may represent an added value in the management of the patient with CKD-MBD already from the early stages of the disease, before the increase of the routinely used laboratory parameters, 1-84 parathyroid hormone (PTH) and 25-OH-vitamin D (25-OH-vitD), which occur in more advanced stages of the disease.

Extraskeletal Calcifications in Children with Maintenance Peritoneal Dialysis

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, often accompanied by extra-skeletal calcification in adult patients. As increased vascular calcification is predicted to increase cardiovascular mortality and morbidity, the revised Kidney Disease: Improving Global Outcomes guidelines recommend avoiding calcium-containing phosphate chelators. However, extra-skeletal calcification is less commonly noticed in pediatric patients. Here, we report our experience of such a complication in pediatric patients receiving maintenance peritoneal dialysis. Extra-skeletal calcification was noticed at the corneas, pelvic cavity, and soft tissues of the lower leg in 4 out of 32 patients on maintenance peritoneal dialysis. These patients experienced the aggravation of extra-skeletal calcifications during peritoneal dialysis, and 2 of them underwent excisional operations. It is required to monitor extra-skeletal calcifications in children on kidney replacement therapy.

Clinical Decision Support System Based on Hybrid Knowledge Modeling: A Case Study of Chronic Kidney Disease-Mineral and Bone Disorder Treatment

Clinical decision support systems (CDSSs) represent the latest technological transformation in healthcare for assisting clinicians in complex decision-making. Several CDSSs are proposed to deal with a range of clinical tasks such as disease diagnosis, prescription management, and medication ordering. Although a small number of CDSSs have focused on treatment selection, areas such as medication selection and dosing selection remained under-researched. In this regard, this study represents one of the first studies in which a CDSS is proposed for clinicians who manage patients with end-stage renal disease undergoing maintenance hemodialysis, almost all of whom have some manifestation of chronic kidney disease–mineral and bone disorder (CKD–MBD). The primary objective of the system is to aid clinicians in dosage prescription by levering medical domain knowledge as well existing practices. The proposed CDSS is evaluated with a real-world hemodialysis patient dataset acquired from Kyung Hee University Hospital, South Korea. Our evaluation demonstrates overall high compliance based on the concordance metric between the proposed CKD–MBD CDSS recommendations and the routine clinical practice. The concordance rate of overall medication dosing selection is 78.27%. Furthermore, the usability aspects of the system are also evaluated through the User Experience Questionnaire method to highlight the appealing aspects of the system for clinicians. The overall user experience dimension scores for pragmatic, hedonic, and attractiveness are 1.53, 1.48, and 1.41, respectively. A service reliability for the Cronbach’s alpha coefficient greater than 0.7 is achieved using the proposed system, whereas a dependability coefficient of the value 0.84 reveals a significant effect.

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

Vasculature plays a key role in bone development and the maintenance of bone tissue throughout life. The two organ systems are not only linked in normal physiology, but also in pathophysiological conditions. The chronic kidney disease–mineral and bone disorder (CKD-MBD) is still the most serious complication to CKD, resulting in increased morbidity and mortality. Current treatment therapies aimed at the phosphate retention and parathyroid hormone disturbances fail to reduce the high cardiovascular mortality in CKD patients, underlining the importance of other factors in the complex syndrome. This review will focus on vascular disease and its interplay with bone disorders in CKD. It will present the very late data showing a direct effect of vascular calcification on bone metabolism, indicating a vascular-bone tissue crosstalk in CKD. The calcified vasculature not only suffers from the systemic effects of CKD but seems to be an active player in the CKD-MBD syndrome impairing bone metabolism and might be a novel target for treatment and prevention.

CKD-MBD und sekundärer Hyperparathyreoidismus (Teil 1)

ZUSAMMENFASSUNGDer Begriff CKD-MBD (Chronic Kidney Disease – Mineral Bone Disorder) ist seit einigen Jahren für Störungen des Kalzium-Phosphat-Stoffwechsels und der damit verbundenen Risiken für das Mineral-Knochen- und Herz-Kreislauf-System bei chronischen Nierenerkrankungen bekannt. Die Bezeichnung entstand nach einem Paradigmenwechsel in der Pathophysiologie des sekundären Hyperparathyreoidismus und da neue Akteure wie FGF23 und Klotho gefunden wurden, die eine wichtige Rolle bei der Entstehung der Störungen spielen. Das wachsende Verständnis der Zusammenhänge zwischen den neuen Akteuren und Kalzium, Phosphat, Vitamin D und Vitamin K2 und der Verkalkung von Gefäßen und Weichteilen beeinflusste unweigerlich unsere Therapien. Dieser erste Teil des Beitrags verschafft einen Überblick über die neuesten Erkenntnisse zum Phosphat-Sensing, die Rolle von FGF23 und Klotho und die Besonderheiten des Vitamin-D- und Vitamin-K-Stoffwechsels bei Gesundheit und chronischer Nierenerkrankung.

CKD-MBD und sekundärer Hyperparathyreoidismus (Teil 2)

ZUSAMMENFASSUNGDer Begriff CKD-MBD (Chronic Kidney Disease – Mineral Bone Disorder) ist seit einigen Jahren für Störungen des Kalzium-Phosphat-Stoffwechsels und der damit verbundenen Risiken für das Mineral-Knochen- und Herz-Kreislauf-System bei chronischen Nierenerkrankungen bekannt. Die Bezeichnung entstand nach einem Paradigmenwechsel in der Pathophysiologie des sekundären Hyperparathyreoidismus und da neue Akteure wie FGF23 und Klotho gefunden wurden, die eine wichtige Rolle bei der Entstehung der Störungen spielen. Das wachsende Verständnis der Zusammenhänge zwischen den neuen Akteuren und Kalzium, Phosphat, Vitamin D und Vitamin K2 sowie der Verkalkung von Gefäßen und Weichteilen beeinflusste unweigerlich unsere Therapien. Dieser zweite Teil des Beitrags verschafft einen Überblick über die Implikationen der neuen pathophysiologischen Erkenntnisse, v. a. im Hinblick auf neue Therapeutika für eine optimale Therapie von Patienten mit CKD-MBD.

Bone Biomarkers in Mucopolysaccharidoses

The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.