Osteocalcin: A bone protein with multiple endocrine functions.

Bones are now recognised as endocrine organs with diverse functions. Osteocalcin, a protein primarily produced by osteoblasts, has garnered significant attention. Research into osteocalcin has revealed its impact on glucose metabolism and its unexpected endocrine role, particularly in its undercarboxylated form (ucOC).

Intravenous iron treatment fuels chronic kidney disease-induced arterial media calcification in rats.

Arterial media calcification is a severe cardiovascular complication commonly manifesting in patients with chronic kidney disease (CKD). Patients with CKD frequently undergo intravenous iron therapy to address iron deficiency. Iron is suggested to be sequestered in vascular cells, potentially leading to oxidative (lipid) stress and cell death, which are recognized as key contributors to arterial calcification.

Defining the molecular response to ischemia-reperfusion injury and remote ischemic preconditioning in human kidney transplantation.

Background: Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC.

Dietary protein intake and the tubular handling of indoxyl sulfate.

Background And Hypothesis: Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown.

Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies.

Key Points: No correlation was observed between pruritus severity and serum phosphate or response to placebo or difelikefalin in patients with CKD-associated pruritus undergoing hemodialysis. Difelikefalin improved itch versus placebo irrespective of baseline serum phosphate.

Background: CKD-associated pruritus (CKD-aP) has historically been associated with elevated serum phosphate (sP).

Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity.

Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial dysbiosis in individuals with CKD. This narrative review explores the underlying mechanisms through which physical activity may favorably modulate microbial health, either through direct impact on the gut or through interorgan crosstalk.

Ten tips on how to assess bone health in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) experience a several-fold increased risk of fracture. Despite the high incidence and the associated excess morbidity and premature mortality, bone fragility in CKD, or CKD-associated osteoporosis, remains a blind spot in nephrology with an immense treatment gap. Defining the bone phenotype is a prerequisite for the appropriate therapy of CKD-associated osteoporosis at the patient level.

Vitamin D Metabolites Before and After Kidney Transplantation in Patients Who Are Anephric.

Rationale & Objective: Kidneys are vital for vitamin D metabolism, and disruptions in both production and catabolism occur in chronic kidney disease. Although vitamin D activation occurs in numerous tissues, the kidneys are the most relevant source of circulating active vitamin D. This study investigates extrarenal vitamin D activation and the impact of kidney transplantation on vitamin D metabolism in patients who are anephric.

Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS.

Introduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear.

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Purpose Of Review: Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD.

Evaluating Osteoporosis in Chronic Kidney Disease: Both Bone Quantity and Quality Matter.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality.

The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD.

Chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients.

Background: Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year.

Methods: Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209).

Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study.

Background: Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD).

Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

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.

Phenylacetylglutamine and trimethylamine N-oxide: Two uremic players, different actions.

Background: Chronic kidney disease (CKD) patients exhibit a heightened cardiovascular (CV) risk which may be partially explained by increased medial vascular calcification. Although gut-derived uremic toxin trimethylamine N-oxide (TMAO) is associated with calcium-phosphate deposition, studies investigating phenylacetylglutamine's (PAG) pro-calcifying potential are missing.

Methods: The effect of TMAO and PAG in vascular calcification was investigated using 120 kidney failure patients undergoing living-donor kidney transplantation (LD-KTx), in an observational, cross-sectional manner.

Inflammation and gut dysbiosis as drivers of CKD-MBD.

Two decades ago, Kidney Disease: Improving Global Outcomes coined the term chronic kidney disease-mineral and bone disorder (CKD-MBD) to describe the syndrome of biochemical, bone and extra-skeletal calcification abnormalities that occur in patients with CKD. CKD-MBD is a prevalent complication and contributes to the excessively high burden of fractures and cardiovascular disease, loss of quality of life and premature mortality in patients with CKD. Thus far, therapy has focused primarily on phosphate retention, abnormal vitamin D metabolism and parathyroid hormone disturbances, but these strategies have largely proved unsuccessful, thus calling for paradigm-shifting concepts and innovative therapeutic approaches.

Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial.

Background: Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Haemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicentre VitaVasK trial analysed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CACs) and thoracic aortic calcifications (TACs).

MicroRNAs: emerging biomarkers and therapeutic targets of bone fragility in chronic kidney disease.

Bone fragility is highly prevalent, yet underdiagnosed in patients with chronic kidney disease. Incomplete understanding of the pathophysiology and limitations of current diagnostics contribute to therapeutic hesitation, if not nihilism. This narrative review addresses the question of whether microRNAs (miRNAs) may improve therapeutic decision making in osteoporosis and renal osteodystrophy.