Chronic Kidney Disease Mineral Research Articles

Effects of Secondary Hyperparathyroidism Treatment on Improvement in Anemia: Results from the MBD-5D Study.

ObjectivesAnemia is an important prognostic factor in hemodialysis patients. It has been reported that parathyroidectomy ameliorates anemia and reduces the requirement of postoperative erythropoiesis-stimulating agents. The objective of this study was to assess the effect of cinacalcet, which is considered as a pharmacological parathyroidectomy, on anemia in hemodialysis patients.MethodsWe used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism; the criteria were: intact parathyroid hormone concentrations ≥ 180 pg/mL or use of an intravenous or oral vitamin D receptor activator. All patients were cinacalcet-naïve at study enrollment. The main outcome measure was achievement of the target hemoglobin level (≥10.0 g/dL), which was measured repeatedly every 6 months. Cinacalcet exposure was defined as cumulative time since initiation. Both conventional longitudinal models and marginal structural models were adjusted for confounding factors.ResultsAmong 3,201 cinacalcet-naïve individuals at baseline, cinacalcet was initiated in 1,337 individuals during the follow up. Cinacalcet users were slightly younger; included more patients with chronic glomerulonephritis and fewer with diabetes; were more likely to have a history of parathyroidectomy; and were more often on activated vitamin D agents, phosphate binders, and iron supplements. After adjusting for both time-invariant and time-varying potential confounders, including demographics, comorbidities, comedications, and laboratory values, each additional 6-month duration on cinacalcet was associated with a 1.1-fold increase in the odds of achieving the target hemoglobin level.ConclusionsCinacalcet may improve anemia in chronic hemodialysis patients with secondary hyperparathyroidism, possibly through pathways both within and outside the parathyroid hormone pathways. Further investigations are warranted to delineate the roles of cinacalcet not only in the management of chronic kidney disease–mineral and bone disorder but also in anemia control.

Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis.

Chronic kidney disease mineral and bone disorder (CKD-MBD) is associated with increased morbidity and mortality. Several cross-sectional studies investigated the association of serum sclerostin levels with mortality and vascular calcification. We aimed to investigate the effect of sclerostin on cardiovascular events (CVE), all-cause/cardiovascular mortality and vascular calcification in patients with CKD through systematic review and meta-analysis. The primary outcome was the association between sclerostin level and development of fatal and nonfatal CVE and all-cause mortality. A literature search was performed using electronic databases Medline Ovid/Medline, PubMed/Medline, EMBASE and ISI Web of Science. Extracted hazard ratios from the included study protocols were pooled separately using the random-effects model (DerSimonian Laird). The equivalent z test was performed for each pooled HR, and if p<0.05 it was considered statistically significant. In our final analysis, we included nine observational prospective studies involving 1788 patients (minimum 91 and maximum 673 patients). For the all-cause mortality, three studies with 503 patients showed that sclerostin levels were not significantly associated with all-cause mortality risk (HR=1.01, 95% CI 0.99-1.03, p=0.16; heterogeneity χ 2=12.24, I 2=84%, p=0.002). For cardiovascular mortality, two studies with 412 patients showed that sclerostin levels were not significantly associated with cardiovascular mortality risk (HR=1.03, 95% CI 0.99-1.07, p=0.17; heterogeneity χ 2=10.74, I 2=91%, p=0.001). Although the studies are mostly small in size, heterogeneous and have conflicting results, we have demonstrated that serum sclerostin levels were not associated with all-cause and cardiovascular mortality.

The role of bone biopsy for the diagnosis of renal osteodystrophy: a short overview and future perspectives.

Chronic kidney disease (CKD) patients present specific bone and mineral metabolism disturbances, which account for important morbidity and mortality. The term renal osteodystrophy, classically used for the nomination of CKD-associated bone disorder, has been limited to the histologic description of bone lesions, requiring the use of bone biopsy. Biochemical markers and imaging tools do not adequately predict the complex bone changes that are observed in renal osteodystrophy. Parathyroid hormone, which is a universally used biomarker of bone turnover in clinical practice, lacks specificity and sensitivity. Therefore, tetracycline double-labelled transiliac bone biopsy, with bone histology and histomorphometric evaluation, remains the best clinical tool to discriminate bone turnover and to evaluate the other dimensions of renal osteodystrophy. This review will focus on the value of classic bone histomorphometric analysis of trabecular bone in CKD patients and unfold new perspectives of this diagnostic tool, including cortical bone evaluation and bone tissue immunohistochemistry.

Ergocalciferol versus calcitriol for controlling chronic kidney disease mineral bone disorder in stage 3 to 5 CKD: A randomized controlled trial

To compare the efficacy and safety of ergocalciferol and calcitriol in stage 3 to 5 chronic kidney disease (CKD) patients, a randomized, prospective, controlled, open-labeled study was designed. 204 patients were enrolled into the present study with following-up duration of 33.2±3.8 months. Patients in Group VitD2 (n=104) and Group aVitD3 (n=100) were treated by ergocalciferol and calcitriol, respectively. The 25-hydroxyvitamin D levels of group VitD2 increased significantly from 15.14±7.46 to 37.32±10.49ng/ml (P<0.001, t=−19.692) and increased more (P<0.001, t=−14.982) than those of group aVitD3, which increased from 14.90±6.15 to 18.08±7.55ng/ml. Maintenance target levels of serum calcium, phosphorus, and intact parathyroid hormone as the primary outcome measure did not show significant difference in frequencies between two groups. In summary, treatment of CKD-mineral and bone disorders in CKD patients at stages 3 to 5 using ergocalciferol has a similar long-term efficacy and safety profile as calcitriol.

Nicotinamide and phosphate homeostasis in chronic kidney disease.

Higher serum phosphate concentration is a central driver of the chronic kidney disease (CKD) mineral bone disorder (MBD). Although phosphate binders are commonly used to lower phosphate, they are minimally effective in CKD. Nicotinamide (vitamin B3) decreases intestinal phosphate transport in animals. Its efficacy and safety in CKD is uncertain. We review data differentiating nicotinamide from nicotinic acid (niacin) and compare the metabolism and side-effect profile of each. Several recent studies have tested the safety and efficacy of nicotinamide in patients with CKD and the general population. Available data on efficacy and safety, gaps in knowledge, and ongoing studies to address them are described. Nicotinamide is a novel potential tool to treat hyperphosphatemia in patients with CKD, but additional data on safety and efficacy are required before widespread clinical use.

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors.

NKF/CRN Message From Chairperson Welcome Summer

Welcome summer! As I enjoy the summer fun, I want to assure you that I am continuing my focus on communication from the NKF/CRN Executive Committee to all regional and local council members. I am also working on more communication options to reach CRN members that do not have a local council in their area. If you are a CRN member who this applies to please contact me with what communication modalities would be best for you. In 2015, we began working on some large projects: the KDOQI Evidence Analysis Project and the National Renal Diet revision. Both of these joint NKF/AND endeavors are ongoing in 2016, hope to have specific updates to pass along to you toward the end of the year. I am excited that I have received e-mails from members interested in working on the low-cost meal plan project. The member volunteers should be underway by the time of this publication, and I look forward to sharing the results with all CRN membership. Some other topics that you may be interested include the following: emergency meals with emphasis on food safety, low literacy educational material, and cooking for one or two. If these topics sound appealing to you and you would like to participate on a committee please contact me or your regional CRN Executive Committee representative. A listing of regions can be found on the NKF Web site professional/dietitian. We are working with the NKF to provide a research grant to a dietitian. Funding is dedicated to a renal dietitian whose research is directed to evaluating the care of the chronic kidney disease patient with the associated comorbidities of iron-deficiency anemia or chronic kidney disease–mineral and bone disorder. The NKF/CRN Executive Committee Region Representatives positions for regions II and IV are currently open and accepting nominations through September 15, 2016. These are the states for each of the open regional representative positions. Below is a description of the Region Representative. If you have an interest or would like to nominate someone please act now. Region II includes: Alabama, District of Columbia, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, West Virginia, Bahamas, Caribbean, Europe, Puerto Rico. Region IV includes: Arkansas, Louisiana, New Mexico, Oklahoma, Texas, Mexico, Central America, South America. Position Description•Represents NKF/CRN in respective regions as a liaison with NKF and local CRN councils and membership regarding opportunities and concerns.•Provides communication between the national and local NKF/CRN members to include: Executive Committee projects for professional and patient education, opportunities for project involvement, policy changes, and Advocacy Alerts. Communicate with local NKF/CRN councils at least quarterly.•Attends the Executive Committee conference at the NKF Spring Clinical Meeting and conference calls throughout the term year.•Chairs and/or participates in activities of the Executive Committee including: NKF Web site communications, publications, membership, professional promotion, professional recognition awards, patient education, research and/or professional resources.•Maintains effective communication with Executive Committee members especially with your Alternate Region Representative. Nominations for CRN Awards have been in progress for past several months. Please check the NKF Web site professional/dietitian/awards for deadlines to nominate a colleague for outstanding work as a nephrology dietitian. As always, feel free to contact me with any question or comment. Have a healthy, safe, and fun summer. I look forward to more updates to pass along in the fall.

Recent Clinical Trials of Pharmacologic Cardiovascular Interventions in Patients with Chronic Kidney Disease: An Update.

As a consequence of both traditional and non-traditional risk factors, cardiovascular disease is over-represented, and the leading cause of mortality, among patients with Chronic Kidney Disease (CKD). Whilst recommendations for reducing cardiovascular risk in the general population exist, their applicability to the CKD population is questionable due to the exclusion of CKD patients from the majority of contemporary cardiovascular interventional studies. The aim of this review is to critically evaluate the literature regarding pharmacologic cardiovascular interventions in patients with CKD, with an emphasis on studies published since our 2008 review. Interventions discussed include erythropoiesis-stimulating agents (TREAT, U.S. Normal Hematocrit, CHOIR, CREATE, Palmer meta-analysis); statins (SHARP, AURORA, PPP, 4D, ALERT); Fibrates (VA-HIT); Folic Acid (ASFAST, US FOLIC acid trial, HOST); Antihypertensive Agents, Including Angiotensin-Converting Enzyme Inhibitors, angiotensin-receptor blockers, Beta-blockers and Combination therapy (Cice et al, FOSDIAL, Agarwal et al, ONTARGET); sevelamer (DCOR); Cinacalcet (ADVANCE, EVOLVE, Cunningham meta-analysis); Anti-oxidants (SPACE, HOPE, ATIC); Aspirin (HOT study re-analysis); vitamin D analogues (PRIMO); and multidisciplinary intervention (LANDMARK). Unfortunately, there remains a paucity of evidence in this area and a large number of methodologically poor quality studies with negative results. It is possible that these interventions do not have the same positive effect in CKD patients due to differences in the pathogenesis driving cardiovascular disease burden, such as altered bone metabolism and calcific vascular disease. Further well-designed studies with appropriately selected study populations and patient level outcomes are required. Until such time, physicians must consider on an individual patient basis the appropriateness of these interventions.

Novel biological markers of bone: from bone metabolism to bone physiology.

Biochemical markers of bone turnover have been used for decades in the management of bone diseases, to assess the prognosis of these conditions and to monitor treatments. The new markers, however, also reflect specific physiological mechanisms in the bone or other organs. Periostin may be more specific to the periosteum; cathepsin K is an osteoclastic enzyme that may be involved in the cardiovascular system and joints; Dickkopf-1 is involved in bone formation and vascular calcification; sclerostin is a major regulator of bone formation in response to mechanical loading and may also play a role in chronic kidney disease bone and mineral disorder; sphingosine-1-phosphate is a lipid mediator interacting with bone resorption. Some of the bone markers are in fact hormones produced by the bone that affect various physiological and pathological functions in other organs. Thus, osteocalcin is produced by osteoblasts and participates in the regulation of insulin sensitivity and fertility in men. Fibroblast growth factor 23 is produced by osteocytes to regulate phosphorus and 1,25(OH)2D3, but it also plays a major role in the adverse consequences of declining renal function, in particular with respect to the myocardium. Micro RNAs are single-stranded RNAs that regulate several pathways, including the development timing, organogenesis, cell apoptosis, proliferation and differentiation. Their serum concentration may reflect the links between bone physiology and certain conditions in other organs, for example, the cardiovascular system.

Single-Center Open-Label Randomized Study of Anemia Management Improvement in ESRD Patients with Secondary Hyperparathyroidism

Background Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD]) are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs) to correct hemoglobin (Hb) may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD) (Optimal ESRD Treatment) study will assess whether lowering of parathyroid hormone (PTH) is associated with a reduction in ESA consumption. Methods The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design) enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH) 300–540 pg/mL and Hb 10–11.5 g/dL will be randomized 1:1 to strict PTH control (150–300 pg/mL) versus standard care (PTH range 300–540 pg/mL). Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation) and Hb (10–11.5 g/dL). Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. Conclusions The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

Effect of parathyroid hormone on serum magnesium levels: the neglected relationship in hemodialysis patients with secondary hyperparathyroidism

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is an important complication in patients with end-stage renal disease. Since recent studies have shown that magnesium (Mg) disturbance plays an important role in CKD–MBD and cardiovascular mortality, the interest on magnesium has grown recently. Although much concern focused on the effect of Mg on parathyroid hormone (PTH) levels, however, the influence of PTH on serum Mg levels is nearly unexplored. To evaluate the effect of PTH on serum Mg levels, we first described the relationship between serum Mg and PTH in secondary hyperparathyroidism. Besides, we also monitored the changes of serum Mg concentration after parathyroidectomy (PTX) in 23 patients. In our study, we found that hypermagnesemia (>2.5 mg/dL) occurred in up to 44% of cases and hypomagnesemia did not present. No statistically significant correlations were found between serum Mg levels and PTH (r = −0.143, p = 0.134). Correlation analysis and regression analysis suggested that the derangement of magnesium homeostasis was consistent with the derangement of calcium/phosphorus homeostasis. However, after PTX, serum magnesium levels dropped immediately after the surgery, minimally at the first day and gradually restored from the third day. The changes of serum Mg after surgery was positive correlated with the changes of serum phosphate (r = 0.558, p = 0.003). Taken altogether, our data suggested that the therapeutic strategies to achieve optimum serum magnesium levels in CKD-MBD should take into account the varying stages of disease development since PTH could also influence magnesium metabolism and this problem might be important in severe secondary hyperparathyroidism.

Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients

Vascular calcifications (VCs) and fractures are major complications of chronic kidney disease. Hemodialysis patients have a high prevalence of atrial fibrillation (AF) and an increased risk of thromboembolism, which should be prevented with warfarin, a drug potentially causing increased risk of VCs and fractures. Aim of this study is evaluating, in hemodialysis patients with and without AF, the prevalence of VCs and fractures, as well as identifying the associated risk factors. A total of 314 hemodialysis patients were recruited, 101 with documented AF and 213 without AF. Comorbidities, chronic kidney disease mineral and bone disorder blood tests and therapies were collected. Vertebral quantitative morphometry was carried out centrally for the detection of fractures, defined as vertebral body reduction by ≥20%. In the same radiograph, the length of aortic calcification was also measured. Logistic regression models were applied for evaluating the independent predictors of presence of VCs and vertebral fractures. In our population VCs were very common (>85%). Severe VCs (>10cm) were more common in patients with AF (76%) than in patients without (33%). Vertebral fractures were present in 54% of patients. Multivariable analysis showed that AF (OR 5.41, 95% CI 2.30-12.73) and 25(OH) vitamin D <20ng/mL (OR 2.05, 95% CI 1.10-3.83) were independent predictors of VCs. Age (OR 1.04/year, 95% CI 1.01-1.07) and male gender (OR 1.76, 95% CI 1.07-2.90) predicted vertebral fractures. Hemodialysis patients had an elevated prevalence of severe VCs, especially when affected by AF. Low vitamin D levels were strongly associated with severe VCs. Prevalence of vertebral fractures was also remarkably high and associated with older age and male gender.

Medical Nutrition Therapy for Chronic Kidney Disease Improves Biomarkers and Slows Time to Dialysis

To investigate whether medical nutrition therapy (MNT) provided by a registered dietitian experienced in chronic kidney disease (CKD) slows the progression of disease and improves nutrition-related biomarkers. Retrospective cohort study. The cohort included 265 participants from a regional nephrology center in a rural state; 147 of who received MNT were compared to a group that did not receive MNT and had started dialysis over a 10-year period. MNT by a registered dietitian with expertise in CKD. Average time to dialysis, based on stage of CKD at baseline, was compared between groups. In addition, the effect of MNT on the change in biochemical measures for estimated glomerular filtration rate, blood urea nitrogen, albumin, CKD Mineral and Bone Disorder (MBD) markers (phosphorous, calcium, and intact parathyroid hormone) at baseline and at follow-up (dialysis initiation or most recent laboratories if dialysis was not started) was assessed. MNT group had less of a decline in estimated glomerular filtration rate than the non-MNT group (0.3 vs. 9.9mL/minute/1.73 m(2), respectively) a mean difference of 9.6 (P<0.001). When adjusted for stage using linear regression, the mean difference was greater (11.4, P<.001). Using survival analysis and Cox proportional hazards regression, the non-MNT group was 3.15 more likely to initiate dialysis. Stratified by Stages 3 and 4 that hazard ratio increased (3.47 and 3.45, respectively). Albumin and markers of CKD-MBD were more likely to be within normal limits in the MNT group. The results indicate that better outcomes occur when MNT is given at CKD Stage 3 or 4 rather than CKD Stage5. Results suggest that people with CKD who received MNT were less likely to start dialysis and had improved nutritional biomarkers than participants who did not receive MNT.

Effect of individual health education on hyperphosphatemia in the Hakkas residential area

The Hakka are a sub-ethnicity with unique diet customs in South China. This study investigated hyperphosphatemia in hemodialysis patients in relation to the current Hakka dietary customs and explored health education patterns for hyperphosphatemia control. Two continuous cross-sectional surveys were conducted among the local patients on dialysis. After the first survey, the patients with hyperphosphatemia were semi-randomized into regular (group 1) and individual (group 2) education groups. Regular health education was conducted for both groups. In group 2, the awareness of health knowledge and dietary customs was investigated using a self-designed questionnaire. Based on the questionnaire, individual dietary guidance was given. The second survey was performed after 3 months. In the first survey, a high-phosphorus diet was found in all 46 patients with 43 (93.5%) diagnosed with hyperphosphatemia. In group 1 and group 2, 15 patients and 25 patients completed the two surveys, respectively. In group 1, no patient changed their dietary habits; however, in group 2, some patients did. The level of serum inorganic phosphorus in group 1 increased significantly. In group 2, the data remained stable; the awareness rate of chronic kidney disease–mineral and bone disorder (CKD–MBD) increased, and six patients with good compliance showed decreased serum inorganic phosphorus (p = 0.046). High-phosphorus dietary customs and low CKD–MBD knowledge awareness are important reasons for the difficulty in hyperphosphatemia control of patients on dialysis in the Hakka region. Individual health education led by medical staff might be helpful in hyperphosphatemia control, but the pattern still needs further exploration.

Relationship between mild-to-moderate chronic kidney disease and decreased bone mineral density in Chinese adult population.

Several studies have shown ethnic differences in bone and mineral metabolism in healthy people and patients with chronic kidney disease (CKD). However, there have been few studies regarding CKD and bone mineral density (BMD) in Chinese population. We aimed to explore the relationship between mild-to-moderate CKD and decreased BMD in Chinese adult population. A total of 24,002 adults were enrolled in this cross-sectional study. Mild-to-moderate CKD was defined as 30 < estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) or eGFR ≥ 60 mL/min/1.73 m(2) with proteinuria greater than 1+. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine. Either osteopenia or osteoporosis was defined as decreased BMD. Multivariate logistic regression analysis was used to estimate the associations with decreased BMD. The subjects comprised 71.5 % men and 28.5 % women, the age was 49.9 ± 13.9 years. The overall prevalence of CKD was 2.9 %. Decreased BMD was 22.1, 19.9 % had osteopenia, and 2.2 % had osteoporosis. The percentage of patients with decreased BMD, osteopenia and osteoporosis were statistically higher (P < 0.05) in CKD patients compared with those of non-CKD participants, which was 29.5 versus 21.9 %, 25.9 versus 19.8 % and 3.6 versus 2.1 %, respectively. The risk for decreased BMD increased with CKD in a simple logistic analysis. However, the correlation disappeared after adjusted for age, sex, smoking, drinking, hypertension, diabetes and obesity. Subjects with worse renal function have significantly lower BMD, but after adjusted for confounders, mild-to-moderate CKD is not independently associated with decreased BMD.

A new player in chronic kidney disease mineral and bone disorder: tenascin-C.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a condition frequently observed in CKD. The search for a reliable and easy to use biomarker in the diagnosis of CKD-MBD is continuing. Tenascin-C (TN-C) is an important extracellular (ECM) protein synthesized by osteoblasts during bone growth and morphogenesis. The purpose of this study was to assess the relation between inflammation and MBD and TN-C in HD patients and to identify a new marker that can be used to help diagnose CKD-MBD. 136 HD patients and 22 healthy controls were enrolled in this cross-sectional, observational multicenter study. Once patients' demographic and biochemical parameters had been recorded, peripheral blood samples were collected for TN-C measurement before the mid-week HD session. The relationship between TN-C levels and demographic and biochemical parameters was then assessed. TN-C levels were significantly higher in the HD patient than in the control group (P&lt;.001). Intact parathormone (iPTH) affected TN-C levels in the HD patient group. TN-C levels was significantly higher in both the high (&gt;300 pg/ml) and low iPTH groups (&lt;150 pg/ml) compared to the 150-300 pg/ml iPTH group (P&lt;.001, &lt;.001 respectively). This study showed, for the first time in the literature, high levels of TN-C in the low and high iPTH groups and that this elevation was associated with iPTH. We think that if our study is supported by further research, TN-C can be a biomarker capable of use in diagnosing CKD-MBD.

Bone kidney interactions.

The fact that bone disease and kidney disease co-exist is well known. Formally, this inter-relationship is called chronic kidney disease mineral bone disorder or CKD-MBD. Traditionally, it was thought that bone played a passive role in CKD-MBD - specifically that kidney disease caused disordered mineral metabolism which resulted in bone disease and ultimately fractures. More recently however our understanding of bone function in general and the role that bone plays in CKD-MBD in particular, has changed. This chapter will briefly review epidemiology of fractures in chronic kidney disease (CKD) and the roles that imaging and measuring markers of mineral metabolism can play in assessing fracture risk. We will then review more recent data consistent with the concept MBD occurs early in the course of CKD and, via the secretion of novel molecules and/or signalling pathways, the bone can influence other organ systems.

Compromised vertebral structural and mechanical properties associated with progressive kidney disease and the effects of traditional pharmacological interventions

Background/AimsPatients with chronic kidney disease mineral and bone disorder (CKD-MBD) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either bisphosphonates or anti-sclerostin antibody in groups of animals with high or low PTH. MethodsAnimals with progressive kidney disease were left untreated, treated with calcium to lower PTH, zoledronic acid to lower remodeling without affecting PTH, anti-sclerostin antibody, or anti-sclerostin antibody plus calcium. Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35weeks of age by microCT and mechanical testing, respectively. ResultsCKD with high PTH resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum PTH. Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with PTH-suppressive treatment. ConclusionsCKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in PTH levels.

Revisiting KDIGO clinical practice guideline on chronic kidney disease—mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference

A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline.

The "phosphorus pyramid": a visual tool for dietary phosphate management in dialysis and CKD patients.

Phosphorus retention plays a pivotal role in the onset of mineral and bone disorders (MBD) in chronic kidney disease (CKD). Phosphorus retention commonly occurs as a result of net intestinal absorption exceeding renal excretion or dialysis removal. The dietary phosphorus load is crucial since the early stages of CKD, throughout the whole course of the disease, up to dialysis-dependent end-stage renal disease.Agreement exits regarding the need for dietary phosphate control, but it is quite challenging in the real-life setting. Effective strategies to control dietary phosphorus intake include restricting phosphorus-rich foods, preferring phosphorus sourced from plant origin, boiling as the preferred cooking procedure and avoiding foods with phosphorus-containing additives. Nutritional education is crucial in this regard.Based on the existing literature, we developed the “phosphorus pyramid”, namely a novel, visual, user-friendly tool for the nutritional education of patients and health-care professionals. The pyramid consists of six levels in which foods are arranged on the basis of their phosphorus content, phosphorus to protein ratio and phosphorus bioavailability. Each has a colored edge (from green to red) that corresponds to recommended intake frequency, ranging from “unrestricted” to “avoid as much as possible”.The aim of the phosphorus pyramid is to support dietary counseling in order to reduce the phosphorus load, a crucial aspect of integrated CKD-MBD management.