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Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.

Background Chronic kidney disease associated mineral bone disorder (CKD-MBD) is one of the major causes of excess morbidity and mortality in hemodialysis patients. The purpose of this study was to investigate whether education about dietary intakes and specific food processing methods affect serum calcium and PTH concentrations in hemodialysis patients. Methods Forty-seven hemodialysis patients were randomly divided into a control and an intervention group. All participants were on individualized phosphate binder therapy. Both groups received education on dietary intake by a trained dietitian. The intervention group received additional education on specific preparation methods of different foodstuffs and consumed two hospital meals prepared according to these methods during hemodialysis. Serum calcium and PTH levels, and vitamin D analog therapy dosage were periodically monitored during the 1-year study period. Results At the baseline of the study, there were no differences between control and intervention groups in serum calcium ( p  = 0.078), serum PTH ( p  = 0.670), and vitamin D analog therapy dosage ( p  = 0.184). At the end of the study, serum calcium was better regulated in the intervention group, resulting in a significant difference between the study groups ( p  = 0.013). This was also confirmed by serum PTH levels in the intervention group, which remained stable until the end of the study ( p  = 0.110). Discussion Additional education on specific food processing techniques may result in improved management of serum calcium and PTH levels, which could ultimately provide better control of secondary hyperparathyroidism in hemodialysis patients. Graphical abstract

Introduction. Chronic kidney disease-mineral and bone disorder is a common complication in hemodialysis patients. The present study was designed to investigate theeffects of flaxseed oil, a rich source of plant omega-3 fatty acid alpha-linolenic acid, on serum markers of bone formation and resorption in hemodialysis patients.Materials and Methods. In this randomized controlled trial, 34 hemodialysis patients were randomly assigned to either the flaxseed oil or the control group. The patients in the flaxseed oil group received 6 g/d of flaxseed oil for 8 weeks, whereas the control group received 6 g/d of medium chain triglycerides oil. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient after a 12- to 14-hour fast and serum concentrations of osteocalcin, osteoprotegerin, N-telopeptide, and receptor activator of nuclear factor kappa B ligand were measured.Results. Serum N-telopeptide concentration decreased significantly up to 17% in the flaxseed oil group at the end of week 8, as compared to baseline (P < .01), and the reduction was significant in comparison with the control group. There were no significant differences between the two groups in the mean changes of serum osteocalcin, osteoprotegerin, or receptor activator of nuclear factor kappa B ligand.Conclusions. This study indicates that daily consumption of 6 g/d of flaxseed oil may reduce bone resorption in hemodialysis patients.

In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2–5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model.

Background High aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment. Methods Twenty-two patients on PD were assigned to spironolactone treatment in dose of 50 mg daily during 12 months. Fifteen PD patients were assigned to control group. Echocardiographic indices, PVW, SBP, DBP (mean values from ABPM) and biochemical parameters such as: aldosterone, osteopontin, IL-6, selectin-P, TGF-β, PTH, MMP-2 were performed at the beginning and after 12 months in spironolactone and control group. Results There were no statistically significant differences in echocardiographic indices, PWV, BP (ABPM readings) and biochemical markers: MMP-2, serum aldosterone, TGF-β, IL-6, selectin-P, PTH level after 12 months of spironolactone treatment. There was statistically significant rise in osteopontin level after 12 months of spironolactone treatment. Episodes of life-threatening hyperkalemia were not reported. Conclusions Aldosterone antagonists use in PD patients seems to be safe. Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients. Further studies are required to determine relationship between mineralocorticoid receptor blockade and mineral-bone disturbances in PD patients.

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001–June 2003) cohort of 58058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

Renal osteodystrophy is a feature of chronic kidney disease (CKD), with increasing prevalence as CKD progresses. This bone disease is responsible for major morbidity, including fractures, and a deterioration in the quality of life and its sequelae. Circulating biomarkers of renal osteodystrophy typically indicate bone turnover, but not other features of bone, like bone volume, mineralization, quality or strength. Bone turnover can be considered to be primarily a reflection of bone cell activity, in particular that of osteoblasts and osteoclasts. Since current treatments for bone disease usually target cellular activity, biomarkers are considered to be able to contribute to the decision-making for treatment and its follow-up. In CKD, one has to consider the impact of a diminished clearance of biomarkers or their altered metabolism, both potentially limiting its clinical use. Here, several aspects of the most frequently used biomarkers of bone turnover are reviewed, with an emphasis on the specific situation represented by CKD. This review is based on the overview lecture at the symposium held in Amsterdam, September 23, 2016: “The Bone In CKD”, organized by the CKD-MBD working group of ERA-EDTA.

Chronic kidney disease—mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins, and dialysis modality. Although extensively studied in hemodialysis (HD) patients, only a few studies exist for peritoneal dialysis (PD) patients. Since most of these older studies contain no bone biopsy data, we studied the pattern of renal osteodystrophy in 41 prevalent PD patients. The most common presentation was adynamic bone disease (49%). There was a significant inverse association between serum sclerostin (a Wnt/β-catenin pathway inhibitor that decreases osteoblast action and bone formation) and the bone formation rate. Bone alkaline phosphatase had the best sensitivity and specificity to detect both high- and low-turnover diseases. The comparison between nondiabetic PD and HD patients, matched by age, gender, parathyroid hormone level, and length of dialysis, revealed low 25-hydroxyvitamin D levels, worse bone mineralization, and low bone turnover in the nondiabetic PD group. Thus, adynamic bone disease was the most frequent type of renal osteodystrophy in PD patients. Sclerostin seems to participate in the pathophysiology of adynamic bone disease and bone alkaline phosphatase was the best serum marker of bone turnover in these patients.

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is the term used to describe a constellation of biochemical abnormalities, bone disturbances that may lead to fractures, and extraskeletal calcification in soft tissues and arteries seen in CKD. This review focuses on the noninvasive diagnosis of renal osteodystrophy, the term used exclusively to define the bone pathology associated with CKD. Transiliac bone biopsy and histomorphometry with double-labeled tetracycline or its derivatives remains the gold standard for diagnosis of renal osteodystrophy. However, histomorphometry provides a ‘window’ into bone only at a single point in time, and is not clinically practical for studying continuous changes in bone morphology. Furthermore, the etiology of fractures in CKD is multifactorial and not fully explained by histomorphometry findings alone. The propensity of a bone to fracture is determined by bone strength, which is affected by bone mass and bone quality; the latter is a term used to describe the structure and composition of bone. Bone quantity is traditionally assessed by dual X-ray absorptiometry (DXA) and CT-based methods. Bone quality is more difficult to assess noninvasively, but newer techniques are emerging and are described in this review. Ultimately, the optimal diagnostic strategy for renal osteodystrophy may be a combination of multiple imaging techniques and biomarkers that are specific to each gender and race in CKD, with a goal of predicting fracture risk and optimizing therapy.