Chronic Kidney Disease Mineral Research Articles

Effect of CKD-MBD phenotype on health-related quality of life in patients receiving maintenance hemodialysis: A cross-sectional study.

ObjectiveThis study aimed to investigate the factors influencing health-related quality of life (HRQoL) in patients with different chronic kidney disease–mineral and bone disorder (CKD–MBD) phenotypes.MethodsPatients undergoing maintenance hemodialysis (MHD) at our center from 1 July to 31 August 2017 were enrolled. Patients who received hemodialysis for less than 3 months or displayed poor compliance, or those with incomplete clinical data were excluded. QoL was evaluated using the Kidney Disease Quality of Life–Short Form (KDQOL-SF™) 1.3 scale. The influential factors were stratified based on different CKB–MBD phenotypes.ResultsThere were 296 patients enrolled. The serum intact parathyroid hormone (iPTH) concentration was 436.40 ± 490.99 pg/mL, serum calcium (Ca) concentration was 2.14 ±0.27 mmol/L, serum phosphorus (P) concentration was 1.81 ± 0.56 mmol/L, the kidney disease and dialysis-related QoL (KDTA) score was 57.07 ± 10.40, and the SF-36 score was 51.45 ± 17.62. Among patients with different CKD–MBD phenotypes, HRQoL was highest in the group with an iPTH concentration of 150 to 300 pg/mL, serum Ca concentration of <2.10 mmol/L, and serum P concentration of >1.78 mmol/L.ConclusionsCKD−MBD phenotypes significantly affected HRQoL. Comprehensive management of serum iPTH, Ca, and P levels is important to improve QoL in patients receiving hemodialysis.

Evidence in chronic kidney disease-mineral and bone disorder guidelines: is it time to treat or time to wait?

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and ‘living’ guidelines), highlight some of the current important CKD–MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the ‘best available evidence’), which may prove useful in the face of the uncertainty over the decision whether ‘to treat’ or ‘to wait’.

New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Sclerostin - a potential new marker of exercise influence on vascular calcification and mineral and bone disorder in hemodialysed adults

Chronic Kidney Disease (CKD) is defined as abnormalities of kidney structure or function, present for &gt;3 months, with implications for health. Amongst CKD complications the most fatal is cardiovascular disease, which together with Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) share a possible origin in Wnt signaling pathway disturbances. Sclerostin, a potent Wnt signaling inhibitor may possibly be used as a potential new marker of exercise influence on vascular calcification and mineral and bone disorder in hemodialysed adults.

Spectrum of mineral bone disorder in patients with CKD stage 3-5 from eastern India

Introduction:&#x0D; Chronic kidney disease mineral bone disorder (CKD-MBD) is a major determinant of CKD associated morbidity and morbidity. We sought to find the spectrum of CKD-MBD in Eastern India.&#x0D; Methodology:&#x0D; This cross-sectional study was conducted at the Department of Nephrology Institute of Postgraduate Medical Sciences and Research Seth Sukhlal Karnani Memorial hospital Kolkata India from June 2013 and July 2014. The patients with newly diagnosed stage 3-5 CKD were evaluated for bone mineral abnormalities. Patients already on some form of phosphate binders or vitamin D analogs were excluded.&#x0D; Results:&#x0D; Total of 242 patients was included. Male to female ratio was 2.1:1. 52.1% had Diabetic nephropathy. Mean eGFR was 26.51±12.33 ml/min/1.73m2. 36.8% had CKD stage 3, 46.7% CKD stage 4 and 16.5 % had CKD stage 5. 56% had hyperphosphatemia (Phosphate&gt;4.0mg/dl). 30% had hypocalcaemia (corrected calcium &lt;8.5mg/dl). 53.4% had Vit D deficiency (25-OH Vit D &lt; 20ng/ml) and 64.9% had hyperparathyroidism (iPTH&gt;65pg/ml). There was a significant negative correlation of eGFR with Phosphate, iPTH and ALP. The distribution of phosphate, ALP and iPTH across CKD stage 3-5 was significantly different; p-&lt;0.001. 21.3% of patients with iPTH more than twice the upper limit of normal had normal ALP. There was no significant difference in serum calcium and 25-OH Vit D levels across CKD stage 3-5.&#x0D; Conclusions:&#x0D; CKD-MBD has a high prevalence. Secondary hyperparathyroidism is the most common type of CKD-MBD. 25-OH Vit D and serum calcium are determined predominantly by diet and exposure to sunlight. ALP can’t serve as a surrogate marker for iPTH.

Cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients below age 5 years .

Management of chronic kidney disease mineral bone disorder (CKD-MBD) in pediatric patients with end-stage renal disease (ESRD) is challenging. While the use of calcimimetics is well-studied in adults on dialysis, few studies have been performed in pediatrics. Little is known about the use of cinacalcet in young children with ESRD. The aim of this study was to report the efficacy and safety of cinacalcet for treatment of secondary hyperparathyroidism in chronic dialysis patients younger than 5 years. We included children aged < 5 years on chronic dialysis, either hemodialysis (HD) or peritoneal dialysis (PD), who were prescribed cinacalcet for more than 1 month. Retrospective chart review was performed to gather demographics, dialysis prescription, relevant mineral imbalance laboratory parameters, and medications. Data was collected for 6 consecutive months. 18 patients (9 male), mean age at initiation of cinacalcet was 2.3 years; 13 PD and 5 HD. Average starting dose of cinacalcet: 6.2 mg daily, 0.55 mg/kg/day. Average time on dialysis was 14.4 months. Parathyroid hormone significantly decreased over the 1st month following initiation of cinacalcet from 929 (IQR 572 - 1,056) to 427 (IQR 256 - 778) pg/mL, p = 0.009. Three patients developed asymptomatic hypocalcemia (Ca < 9.4 mg/dL). Serum phosphorous decreased after initiation, and this was persistent at 6 months. Significant improvement in linear growth was observed while on cinacalcet and growth hormone (GH). Cinacalcet can be effectively used in young children on dialysis with minimal side effects. Good linear growth was seen in patients on cinacalcet and GH therapy. Long-term large scale data is necessary to confirm. Institution-based management algorithm incorporating cinacalcet would be helpful to maintain uniformity in role of cinacalcet for management of CKD-MBD.

Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study.

BackgroundPrior studies have developed a chronic kidney disease–mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients.MethodsWe studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3–5 (2005–15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5–5.5 mg/dL; Ca, 8.4–10.2 mg/dL; PTH, 150–600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2–3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS).ResultsMBD 2/3 above target was observed in 10–14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10–1.82]} and composite events [HR 1.23 (95% CI 1.10–1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28–2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80–1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions.ConclusionsSimultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

Clinical practice guideline on pregnancy and renal disease

Background Chronic kidney disease (CKD) is estimated to affect 3% of pregnant women in high-income countries, (Piccoli et al., 2018, #13860) which equates to between 15,000–20,000 pregnancies per year in England. The prevalence of CKD in pregnancy is predicted to rise in the future due to increasing maternal age and obesity. Although CKD is not a barrier to reproduction in most women, the risk of adverse pregnancy outcomes is increased in women with CKD including pre-eclampsia, fetal growth restriction, preterm delivery and accelerated loss of maternal renal function. CKD impacts on communication, decision-making, and the surveillance and management of women before, during, and after pregnancy. Existing guidance on the management of CKD in pregnancy includes the UK Consensus Group on Pregnancy in Renal Disease (ISBN 978–1,107,124,073) and expert review. Neither Kidney Disease Outcomes Quality Initiative (KDOQI) or National Institute of Health and Care Excellence (NICE) have produced specific guidance on the management of renal disease in pregnancy. Published guidance containing information relevant to the care of women with CKD in pregnancy includes: KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). UK Renal Association Commentary available at: BMC Nephrology 2018; 19: 240. KDOQI Clinical Practice Guideline for Haemodialysis, 2015. KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD, 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis, 2012 KDIGO Guideline for the Care of Kidney Transplant Recipients, 2009. KDIGO Clinical Practice Guidelines for Nutrition in Chronic Renal Failure, 2008. NICE: Intrapartum Care for Women with Existing Medical Conditions or Obstetric Complications and their Babies [NG121], 2019. NICE: Urinary Tract Infection (Lower) Antimicrobial Prescribing [NG109], 2018 NICE: Urinary Tract Infection (Recurrent) Antimicrobial Prescribing [NG112], 2018. NICE: Antenatal Care for Uncomplicated Pregnancies [CG62], 2008, updated 2017. NICE: Vitamin D supplement use in specific population groups [PH56], 2017 NICE: Diabetes in Pregnancy: Management from Pre-conception to the Post-partum Period [NG3], 2015. NICE: Antenatal and postnatal mental health: clinical management and service guidance [CG192], 2014, updated 2018. NICE: Fertility: Assessment and Treatment for People with Fertility Problems, 2013. NICE: Weight management before, during and after pregnancy [PH27], 2010 [additional data from 2017 surveillance available at: https://www.nice.org.uk/guidance/ph11/evidence/appendix-a-summary-of-evidence-from-surveillance-pdf-4671107966] NICE: Hypertension in Pregnancy: Diagnosis and Management [CG107], 2011 (update awaited 2019). UK Renal Association Clinical Practice Guidelines: Undernutrition in Chronic Kidney Disease, June 2019 RCOG: Thrombosis and Embolism During Pregnancy and the Puerperium, Reducing the Risk [Green-Top Guideline 37a], 2015. MBBRACE Confidential Enquiry into Maternal Deaths and Morbidity: lessons learned to inform maternity care (triennial reports) www.european-renal-best-practice.org/content/erbp-documents

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

The Cy/+ rat has been characterized as a progressive model of chronic kidney disease-mineral bone disorder (CKD-MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole-body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium-dependent and sodium-independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33 P radioisotope. Our results show that CKD rats had slightly higher sodium-dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH2 D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi-2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30-week-olds compared with 20-week-olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30-week-old rats compared with 20-week-old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH2 D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings. © 2019 American Society for Bone and Mineral Research.

2017 Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update Implementation: Asia Summit Conference Report

The Kidney DiseaseImproving Global Outcomes (KDIGO) Clinical Practice Guideline on Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD) 2009 provided recommendations on the detection, evaluation, and treatment of CKD-MBD in patients CKD who are and are not undergoing dialysis. Because of the accumulation of evidence since this initial publication, the CKD-MBD Guideline underwent a selective update in 2017. In April 2018, KDIGO convened a CKD-MBD Guideline Implementation Summit in Japan with the key objective to discuss various barriers to the uptake and implementation of the CKD-MBD Guideline in 8 Asian countries/regions. These countries/regions were comparable according to their high-to-middle economic ranking assigned by the World Bank. The discussion took into account the availability of CKD-MBD medication therapies and government health policies that may influence reimbursement and practice patterns in the region. Most importantly, Summit participants developed a framework of multifaceted strategies aimed at overcoming barriers to guideline implementation. The Summit attendees suggested a shared decision-making approach between clinicians and patients in CKD-MBD management, as well as individualized care based on the treatment risk-benefit ratio. The Summit participants also discussed how KDIGO, as a guideline development organization, may work in partnership with local and national nephrology societies to provide education and facilitate implementation of the guideline by clinicians. The conclusions drawn from this Summit in Asia may serve as an important guide for other regions to follow.

Modifying Phosphate Toxicity in Chronic Kidney Disease

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD.

Sotatercept Safety and Effects on Hemoglobin, Bone, and Vascular Calcification

IntroductionPatients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD–MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification.MethodsForty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days).ResultsIn REN-001, frequency of achieving target hemoglobin response (>10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%−57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups.ConclusionIn patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed.

SUN-292 BENEFITS AND HARMS OF VITAMIN D COMPOUNDS IN ADULTS WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS

Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) is a systemic disorder characterised by vitamin D deficiency, elevated parathyroid hormone (PTH) levels, reduced bone quality, and increased fracture risk. Vitamin D therapy is an essential part of the CKD-MBD management. This systematic review was performed to study the effects of vitamin D therapy on fractures, mortality, bone mineral density (BMD), and biochemical markers of CKD-MBD.

Correlation of Radiomorphometric Indices of the Mandible and Biochemical Parameters in Patients with Secondary Hyperparathyroidism Due to Chronic Kidney Disease.

Objective The aim was to correlate radiomorphometric indices and biochemical analyses as an auxiliary method in bone evaluation in male and female patients with chronic kidney disease–mineral and bone disorder (CKD-MBD) and controls. Materials and Methods Nine radiomorphometric indices and four biochemical parameters were obtained: mental index (MI), height at the mental foramen, total mandibular height (THM), panoramic mandibular index (PMI), original height of the mandible, alveolar bone resorption, distance from the mental foramen to the alveolar bone crest (MF-ABC), mandibular cortical index (MCI), trabecular bone pattern, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and Ca × P product (Ca × P). Statistical Analysis The Mann–Whitney U -test, chi-squared test, and Spearman’s correlation were applied at a significance level of 95%. Results There was a moderate negative and significant correlation between MI, PMI, and PTH in female patients with CKD-MBD as well as between THM, MF-ABC, and Ca × P. The MCI and trabecular bone pattern indicated altered bone quality in male patients. Conclusions The radiomorphometric evaluation was an auxiliary, noninvasive method to detect possible alterations in the cortex and mandibular bone trabeculation in male and female patients with CKD-MBD.

Outcome of supplementation of vitamin D on intact parathyroid hormone level in chronic kidney disease patients

Background: Secondary hyperparathyroidism is present in majority of patients with estimated glomerular filtrate rate less than 60 mL/min/1.73 m2. Sustained elevated parathyroid hormone level can cause osteitis-fibrosa-cystica, fracture, hypercalcemia, hyperphosphatemia, and calciphylaxis. Kidney Disease Improving Global Outcome guidelines for Chronic Kidney Disease Mineral and Bone Disorder 2017 recommends treatment with calcitriol or vitamin D analogue if parathyroid hormone level is progressively increasing and remains persistently above the upper limit despite correction of modifiable factors.&#x0D; Objectives: The objective of this study was to determine the mean change in intact parathyroid hormone aftercalcitriol supplementation in patients with chronic kidney disease (stage 3 to 5).&#x0D; Methodology: This prospective observational study enrolled 92 patients with chronic kidney disease stage 3 to 5, not under maintenance hemodialysis. Patients who had intact parathyroid hormone level more than 200 pg/ml, serum phosphate level less than 4.5 mg/dl and corrected serum calcium less than 9.5 mg/dl were selected for the study. They were supplemented with oral calcitriol 0.25μg thrice weekly for three months and intact parathyroid hormone level was measured after three months.&#x0D; Results: Mean intact parathyroid hormone level before supplementation was 332.91 ± 96.046pg/ml and after three months of supplementation with calcitriol was 176.49 ±53.764pg/ml. This finding was statistically significant (Correlation: 0.471, p-value less than 0.05). Thus, supplementation of calcitriol reduced the mean intact parathyroid hormone level in the chronic kidney disease patients in our study.&#x0D; Conclusion: Calcitriol supplementation seems to be an effective measure to reduce intact parathyroid hormone level in chronic kidney disease patients when it remains persistently high despite correction of modifiable factors.

The association of fibroblast growth factor 23 with other factorsof mineral and bone disorder in chronic kidney disease

The association of fibroblast growth factor 23 with other factorsof mineral and bone disorder in chronic kidney disease

The role of uric acid in mineral bone disorders in chronic kidney disease.

Increasing survival in the chronic kidney disease (CKD) population exposes the bone to the cumulative detrimental sequelae of CKD, now defined physiologically and histopathologically as chronic kidney disease mineral bone disorder (CKD-BMD). This disorder is increasingly recognized as a "nontraditional" driver of morbidity and mortality and presents an opportunity to improve CKD outcomes via research. However, recent advances in the literature on this topic have not yet been collected into a single review. Therefore, this report aims to discuss the disordered renal-bone axis in CKD-BMD, molecular and hormonal drivers, novel treatment strategies, and forthcoming research in a clinician-directed format. A key novel topic will be the unique impact of uric acid on CKD-BMD, which is poised to apply extensive existing research in the uric acid domain to benefit the CKD-BMD population.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production

Chronic kidney disease–mineral bone disorder (CKD–MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/β-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial β-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Burden, access and disparities in kidney disease: chronic kidney disease hotspots and progress one step at a time.

The 2019 International Society of Nephrology World Kidney Day theme is Kidney Health for Everyone Everywhere. It focuses on the uneven burden of acute kidney injury and chronic kidney disease (CKD) in different communities, identifies disparities and challenges in access to care and calls for universal health coverage for prevention and early treatment of kidney disease. This topic is fully in line with the Clinical Kidney Journal (ckj) editorial strategy for improving worldwide kidney care without leaving any community behind. Indeed, the first PubMed-recorded use of the term CKD hotspot was in ckj, where it was defined as ‘countries, region[s], communities or ethnicities with higher than average incidence of CKD’. This issue of ckj contains the World Kidney Day editorial as well as contributions that illustrate two concepts: the need to validate biochemical thresholds generated in developed countries in other populations, as exemplified by Kidney Disease: Improving Global Outcomes CKD–mineral and bone disorder parameters in an African population, and the fact that some disease associations characteristic of developing countries may be described initially in developed countries, as exemplified by the association of APOL1 variants with CKD or by minimal change disease secondary to malaria, but have to be validated locally.

Chronic Kidney Disease and Pulse Wave Velocity: A Narrative Review.

Chronic kidney disease (CKD) is associated with excess cardiovascular mortality, resulting from both traditional and nontraditional, CKD-specific, cardiovascular risk factors. Nontraditional risk factors include the entity Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) which is characterised by disorders of bone and mineral metabolism, including biochemical abnormalities of hyperphosphatemia and hyperparathyroidism, renal osteodystrophy, and vascular calcification. Increased arterial stiffness in the CKD population can be attributed amongst other influences to progression of vascular calcification, with significant resultant contribution to the cardiovascular disease burden. Pulse wave velocity (PWV) measured over the carotid-femoral arterial segments is the noninvasive gold-standard technique for measurement of aortic stiffness and has been suggested as a surrogate cardiovascular end-point. A PWV value of 10 m/s or greater has been recommended as a suitable cut-off for an increased risk of cardiovascular mortality. CKD is a risk factor for an excessive rate of increase in aortic stiffness, reflected by increases in PWV, and increased aortic PWV in CKD shows faster progression than for individuals with normal kidney function. Patients with varying stages of CKD, as well as those on dialysis or with a kidney transplant, have different biological milieu which influence aortic stiffness and associated changes in PWV. This review discusses the pathophysiology of arterial stiffness with CKD and outlines the literature on PWV across the spectrum of CKD, highlighting that determination of arterial stiffness using aortic PWV can be a useful diagnostic and prognostic tool for assessing cardiovascular disease in the CKD population.