Renal osteodystrophy: something old, something new, something needed

David, Valentin; Salusky, Isidro B.; Malluche, Hartmut; Nickolas, Thomas L.

doi:10.1097/mnh.0000000000000918

Cited by 3 publications

(1 citation statement)

References 50 publications

(63 reference statements)

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“…In chronic kidney disease (CKD), secondary hyperparathyroidism causes alterations in bone remodeling, mineralization, volume, and growth, known as renal osteodystrophy. Bone alterations are classified based on the degree of remodeling and mineralization into mild forms, fibrous osteitis, osteomalacia, adynamic bone disease, and mixed bone disease [20].…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Secondary hyperparathyroidism: Update

Erick Alexander Cabrera Estrada,

Epitafio Rafael Mestre Sequeda,

Iván Alberto Salas Pinzón

et al. 2024

World J. Adv. Res. Rev.

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Secondary hyperparathyroidism is a clinical condition characterized by an increase in the synthesis and secretion of parathyroid hormone (PTH). Its presentation will be conditioned by the development of stimuli such as hyperphosphatemia, hypocalcemia, vitamin D deficiency, and PTH resistance. The most common cause of secondary hyperparathyroidism is chronic kidney disease, a pathological condition in which all the afore mentioned stimuli converge. Secondary hyperparathyroidism is evidenced by an increase in the size of the parathyroid glands, favored by cellular hyperplasia and hypertrophy. At the bone level, there will be an increase in the quantity and activity of osteoblasts and osteoclasts, leading to bone with unusual structural characteristics. Symptoms related to the disease include itching, bone pain, concentration alteration, and depression. In the long term, patients have a higher risk of cardiovascular mortality. Therapeutic options include calcimimetics, phosphate binders, vitamin D supplements, and surgery.

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Section: Clinical Manifestationsmentioning

confidence: 99%

Secondary hyperparathyroidism: Update

Erick Alexander Cabrera Estrada,

Epitafio Rafael Mestre Sequeda,

Iván Alberto Salas Pinzón

et al. 2024

World J. Adv. Res. Rev.

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Application of artificial intelligence to chronic kidney disease mineral bone disorder

Lederer,

Sobh,

Brier

et al. 2024

Clinical Kidney Journal

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Background The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed toward secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. Methods/Results We describe in this review a novel approach to CKD-MBD combining mathematical modeling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Conclusions Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies in order to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals.

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Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach

Wang,

Di,

et al. 2024

Chinese Medical Journal

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Background: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). Methods: Male 8-week-old C57BL/6J mice were randomly allocated into three groups: control group (n = 5), adenine and high-phosphate (HP) diet group (n = 20), and the optimized adenine-containing diet group (n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). Results: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 (Acer1), alkaline ceramidase 2 (Acer2), prosaposin-like 1 (Psapl1), adenosine A1 receptor (Adora1), and sphingosine-1-phosphate receptor 5 (S1pr5) were successfully validated in mouse femurs by qRT-PCR. Conclusions: Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.

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Renal osteodystrophy: something old, something new, something needed

Cited by 3 publications

References 50 publications

Secondary hyperparathyroidism: Update

Secondary hyperparathyroidism: Update

Application of artificial intelligence to chronic kidney disease mineral bone disorder

Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach

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