Search

Background and Objective: Hyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K + ), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K + chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System., Materials and Methods: Two microsimulation models reflecting the natural history of CKD and HF were used. In both models, K + levels were simulated individually. Based on efficacy (reduction of K + levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (€, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes., Results: SZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of € 3,616 and € 14,749, respectively, obtaining an incremental cost-utility ratio of € 7,605/QALY in CKD and € 15,078/QALY in HF., Conclusions: SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Secondary hyperparathyroidism is one of the most frequent metabolic abnormalities found in patients with chronic kidney disease. The calcium-sensing receptor senses extracellular calcium and is the principal regulator of parathyroid hormone secretion. Cloning of the calcium-sensing receptor led to the development of calcimimetics, drugs that decrease parathyroid hormone secretion through the positive allosteric modulation of this receptor. Cinacalcet was the first oral calcimimetic approved by the US Food and Drug Administration (FDA) in 2004 for the treatment of secondary hyperparathyroidism in adult patients on dialysis. Although cinacalcet has demonstrated safety and effectiveness, it has two main problems: gastrointestinal side effects that result in poor adherence, and the inhibitory action on CYP2D6 with the possibility of interactions with commonly used medications. To address the problem of oral compliance, Etelcalcetide, a small synthetic polycationic peptide IV calcimimetic was introduced in 2017. This drug showed a 10% greater decrease in serum parathyroid hormone values compared to cinacalcet but no better gastrointestinal tolerance, with greater risk of hypocalcemia. Several structural modifications were introduced in cinacalcet to produce a new compound called evocalcet. This drug, which was introduced in Japan in 2018, has considerably enhanced bioavailability and decreased both the inhibitory effect on CYP2D6 and half of the gastrointestinal side effects of cinacalcet. Finally, a novel non-peptidic injectable calcimimetic agent, upacicalcet, became available in Japan in 2021. This agent has greater clearance by hemodialysis and shows no effect on gastric emptying. More studies are needed comparing the old calcimimetics to the new ones to establish their future role in the treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) G5D., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K + ) restriction, bicarbonate correction, diuretics and K + binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap. We report the design and baseline cohort characteristics of this real-world study of hyperkalaemia management decision-making., Methods: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment., Results: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% neither. Most participants (57%) were taking an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or angiotensin receptor/neprilysin inhibitor at baseline. Mineralocorticoid receptor antagonist use was lower (14%)., Conclusions: The prospective TRACK study will shed light on practitioners' hyperkalaemia management decision-making and assess the impact of their decisions on hyperkalaemia recurrence. Understanding practitioners' underlying thought processes will facilitate efforts to improve hyperkalaemia management.ClinicalTrials.gov: NCT05408039., Competing Interests: J.H. and M.P.B. receive salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, which receives research grant/consulting funding from Agios Pharmaceuticals, Alexion Pharma Good Kaisha, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca Pharma India, AstraZeneca Pharmaceuticals, AstraZeneca UK, AstraZeneca, Produtos Farmaceuticos, Atentiv, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma, Beth Israel Deaconess Medical Center, Better Therapeutics, Bionest Partners, Boston Clinical Research Institute, BMS, CellResearch, Cleerly, Colorado Department of Public Health and Environment, Cook Regentec, CSL Behring, Eidos Therapeutics, EPG Communication Holdings, Esperion Therapeutics, Faraday Pharmaceuticals, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Lexicon Pharmaceuticals, LSG, MedImmune, Medpace, Medscape, Merck Sharp & Dohme, Northwell Health, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PPD Development, Prothena Biosciences, Regeneron, Regents of the University of Colorado, Sanifit Therapeutics, Sanofi, Silence Therapeutics, Stanford University, Stealth BioTherapeutics, Brigham & Women's Hospital, Thrombosis Research Institute, UCD iC42 Lab, University of Colorado Denver, University of Pittsburgh, VarmX and WraSer. J.H. also reports owning AstraZeneca stock. N.S., M.B., H.C. and A.-K.S. own AstraZeneca stock. A.B. has received consultant fees and grant/other support from Abbott, Association of the British Pharmaceutical Industry, Accentus Medical, Amgen, Amore Health, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Closer Still Media, Daiichi Sankyo, Health Smart, Janssen, Lattice Point, Lilly, Medtronic, McKinsey, MSD, Napp, Novartis, Novo Nordisk, Pfizer, Remedica, Sanofi Aventis and AirEmail. J.Bover received advisory and/or lecture fees and/or congress travel expenses from AbbVie, Amgen, AstraZeneca, Bayer, CSL-Vifor, GSK, Menarini, Rubió, Sanofi and Theramex. J.Butler has received consultant fees from Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, BMS, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor and Zoll. P.M.F. has received consultant fees and grant/other support from Allena Pharmaceuticals, Alnylam, Amgen, AstraZeneca, Bayer, Gilead, Novo Nordisk, Otsuka Pharmaceuticals, Rocchetta and Vifor Fresenius and royalties as an author for UpToDate. L.F. serves on data safety monitoring boards for Novo Nordisk and Regeneron and owns Amgen stock. M.P.S. has received advisory board fees and honoraria from AstraZeneca, Bayer, Vifor Pharma Group and Boehringer Ingelheim/Lilly. N.T. has received grants/research support from the Canadian Institutes of Health Research, National Institutes of Health, Kidney Foundation of Canada, Bayer, AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceuticals, Research Manitoba, Otsuka Pharmaceutical, Tricida and Lilly; honoraria or consultation fees from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Janssen Pharmaceuticals, Otsuka Pharmaceutical, Prokidney, Roche, Tricida and Lilly; and owns stock in ClinPredict, Klinrisk, Quanta, Marizyme, Mesentech, Renibus Therapeutics, PulseData and Tricida. W.C.W. has received consultant fees from Akebia, Anthos, Ardelyx, AstraZeneca, Bayer Boehringer Ingelheim, Cadrenal, GSK, Merck, Natera, Novartis, Pharmacosmos, Unicycive, Vera and Zydus., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Understanding immune cell dynamics in kidney transplantation may provide insight into the mechanisms of rejection and improve patient management. B cells have gained interest with a special relevance of the "regulatory" subsets and their graft outcome prognostic value. In this study, we aimed to prove that the direct immunophenotyping and target gene expression analysis of kidney transplant patients' fresh whole blood will help to identify graft rejection risk and assist in the monitoring of kidney transplanted patients., Methods: We employed flow cytometry and qPCR techniques to characterize B and T cell subsets within fresh whole blood samples, with particular emphasis on transitional B cells (TrB) identified as CD19 + CD24 hi CD38 hi . TrB are a relevant population in the context of kidney transplantation and are closely associated with regulatory B cells (Bregs) in humans. Patients were monitored, tracking pertinent clinical parameters and kidney-related events, including alterations in graft function and episodes of biopsy proven rejection., Results: Higher percentages of TrB cells at 3 months after transplantation were positively associated with better graft outcomes and lower biopsy-proven acute rejection risk. Furthermore, a novel panel of B cell regulatory associated genes was validated at 3 months post-transplantation by qPCR analysis of peripheral blood mononuclear cell (PBMC) mRNA, showing high predictive power of graft events and prognostic value., Discussion: These findings suggest that monitoring TrB may provide interesting patient management information, improve transplant outcomes, and allow for personalized drug regimens to minimize clinical complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author MF declares that they were an editorial board member of Frontiers, at the time of submission. Thishad no impact on the peer review process and the final decision., (Copyright © 2024 Perezpayá, Garcia, Clos-Sansalvador, Sanroque-Muñoz, Font-Morón, Rodríguez-Martínez, Vila-Santandreu, Bover, Borràs, Cañas and Franquesa.)

Vertebral fractures (VFs) are the most common osteoporotic fractures in the general population, and they have been associated with high mortality, decreased quality of life, and high risk of subsequent fractures, especially when recent, multiple, or severe. Currently, VF diagnosis and classification determine fracture risk and the most appropriate anti-osteoporotic treatment. However, VFs are clearly underdiagnosed, especially in patients with chronic kidney disease (CKD), and CKD-associated osteoporosis has been disregarded until recently. VFs are associated with higher morbidity and mortality, and their prevalence and incidence differ depending on the grade of renal dysfunction (CKD G1-G5) and/or the type of renal replacement therapy (dialysis or transplantation). In addition to classical risk factors [such as higher age, female sex, reduced bone mineral density, diabetes and steroid use], various other factors have been associated with an increased risk of VFs in CKD, including CKD grade, haemodialysis vintage, time since renal transplantation, low or high intact parathyroid hormone and phosphate levels, and/or vitamin D and K 1 deficiencies. Importantly, several clinical societies have recently modified their algorithms according to the fracture risk classification (including the presence of VFs) and determined the most appropriate anti-osteoporotic treatment for the general population. However, there are no specific guidelines addressing this topic in patients with CKD despite an important paradigm shift regarding the prognostic value of bone mineral density in 2017 after the publication of the CKD-Mineral and Bone Disorder Kidney Disease: Improving Global Outcomes guidelines. A proactive attitude towards diagnosis, treatment, and research is proposed to avoid therapeutic nihilism., Competing Interests: L.G. declares receipt of lecture fees from UCB, Amgen, Rubió, Stada, Theramex, Lilly, Abbvie, Astellas, Kyowa Kyrin, and Gebro. M.F. declares financial or non-financial interests from Amgen, Abiogen, and Vifor. P.U. declares receipt of honoraria for advisory boards and speaker meetings from Amgen, Astellas, Astra Zeneca, Baxter, GSK, Theradial, and Vifor Pharma. P.P. declares receipt of lecture fees from UCB, Amgen, Rubió, Lilly, Gebro, and Kyowa Kyrin. J.B. declares receipt of advisory and/or lecture fees from Amgen, Abbvie, Sanofi, CSL-Vifor, Astra Zeneca, Rubió, GSK, and Bayer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Chronic kidney disease (CKD) poses a significant epidemiological challenge, necessitating effective patient management strategies. Nutritional intervention, particularly vitamin D supplementation, has garnered attention for its potential therapeutic utility in CKD. Despite widespread acknowledgment of the importance of vitamin D, particularly in bone and mineral metabolism, its supplementation in CKD patients for non-skeletal purposes remains contentious due to limited evidence. Hypovitaminosis D linked with CKD substantially contributes to disturbances in mineral and bone metabolism, increasing the risks of cardiovascular complications and skeletal disorders. Notably, CKD patients experience progressive vitamin D deficiency, exacerbating as the disease progresses. Guidelines recommend monitoring 25-hydroxyvitamin D (25 (OH)-D) levels due to their correlation with mineral metabolism parameters, although robust evidence for recommending supplementation is lacking. The primary aim of this paper is to focus on the main open questions regarding vitamin D supplementation in CKD, reporting the current evidence concerning the role of vitamin D supplementation in CKD and in renal transplant recipients., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The multidimensional view of disease is fundamental in the care of complex diseases such as chronic kidney disease (CKD). It is appropriate to define and unify concepts that allow the different professionals involved in care to provide a multidisciplinary approach tailored to the needs of each individual. Given the increasing incidence of CKD worldwide and the fact that the disease may progress at different rates, there is a need to establish personalized, comprehensive approaches for each patient and their families at an earlier stage. This approach goes beyond the simple control of uremic symptoms or congestion and consists of addressing not only symptomatic but also functional, social and coping problems at an early stage, facilitating decision making both in the CKD and in acute situations, potentially irreversible or interventions that do not improve life expectancy. To ensure excellence in care, it is important to assess indicators of palliative care and kidney support, such as the presence of advance and shared care planning, the inclusion of psychosocial, ethical, spiritual and bereavement care. This enables the provision of comprehensive, humanized, and high-quality care for patients and their families. Palliative and kidney care is not just about patients in the last days of life. Defining, unifying, and evaluating the concepts will allow them to be applied in a timely manner at each specific moment of the CKD trajectory., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure., Objectives: The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up., Methods: A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death., Results: A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m 2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m 2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death., Conclusions: These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population., Competing Interests: Funding Support and Author Disclosures Dr Bayes-Genis has lectured or participated in advisory boards for Abbott, AstraZeneca, Boehringer-Ingelheim, Bayer, Novartis, Roche Diagnostics, and Vifor. Dr Nuñez has received personal fees or advisory boards from Alleviant, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, NovoNordisk, Rovi, and Vifor CSL. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m 2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism., (Copyright © 2024. Published by Elsevier España, S.L.U.)

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 gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

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. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin-angiotensin-aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.

Introduction: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF)., Methods: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents., Results: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively)., Conclusion: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular ( n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions : In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice., Methods: A national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice., Results: One hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH) 2 D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines ( n  = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range., Conclusion: Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice., Competing Interests: J.B. and M.C. are members of the ckj editorial board. M.F. reports other financial or non-financial interest from Amgen, Abiogen, and Vifor. M.Ga. received payment for lectures/presentation from Baxter, Medtronic, Amicus, BD, Sanofi, Vifor Pharma and support for meetings/travel from Astellas, Sanofi. G.C. received payment for lectures/presentation from Amgen, Vifor, AstraZeneca, Boehringer. G.LM. received payment for lectures/presentation fro Astellas, Vifor, Hansa, Biopharma, Eli-Lily, Travere, GlaxoSmithKline. T.N. received grant support from Amgen and consulting fees from Pharmacosmos. S.F. received consulting fees from Amgen, Myovant, UCB, Amolyt, Radius, Agovos and payment for lectures/presentation from Amgen, UCB, Gedeon Richter. J.B. received consulting fees, payment for lectures/presentation and support for attending meetings and/or travel from AMGEN, Abbvie, Sanofi, CSL-Vifor, Astra-Zeneca, Rubió. M.H. received grants from Diaverum, Resverlogix. M.C.M. received payment for lectures/presentation from Amgen, Vifor Pharma, Abiogen. G.T. reports other financial or non-financial interest from Amgen, Biotest, ABBVIE, Janssen-Cilag, Alexion. The remaining authors have no conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Among the metabolic changes occurring during the course of type 2 diabetes (T2DM) and diabetic kidney disease (DKD), impaired bone health with consequent increased fracture risk is one of the most complex and multifactorial complications. In subjects with diabetic kidney disease, skeletal abnormalities may develop as a consequence of both conditions. In the attempt to define a holistic approach to diabetes, potential effects of various classes of antidiabetic drugs on the skeleton should be considered in the setting of normal kidney function and in DKD. We reviewed the main evidence on these specific topics. Experimental studies reported potential beneficial and harmful effects on bone by different antidiabetics, with few data available in DKD. Clinical studies specifically designed to evaluate skeletal effects of antidiabetics have not been performed; notwithstanding, data gleaned from randomized controlled trials and intervention studies did not completely confirm observations made by basic research. In the aggregate, evidence from meta-analyses of these studies suggests potential positive effects on fracture risk by metformin and glucagon-like peptide-1 receptor agonists, neutral effects by dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and sulfonylureas, and negative effects by insulin and thiazolidinediones. As no clinical recommendations on the management of antidiabetic drugs currently include fracture risk assessment among the main goal of therapy, we propose an integrated approach with the aim of defining a patient-centered management of diabetes in chronic kidney disease (CKD) and non-CKD patients. Future clinical evidence on the skeletal effects of antidiabetics will help in optimizing the approach to a personalized and more effective therapy of diabetes.

Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aguilar, Gifre, Ureña-Torres, Carrillo-López, Rodriguez-García, Massó, da Silva, López-Báez, Sánchez-Bayá, Prior-Español, Urrutia, Paul, Bustos, Vila, Garnica-León, Navarro-González, Mateo and Bover.)

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día)., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease-Mineral and Bone Disorder Update 2017 guideline 4.2.1 stating that the optimal parathyroid hormone levels are not known in these stages. Furthermore, new caution became recommended with regard to the routine use of active vitamin D analogues in early CKD stages and moderate SHPT phenotypes, due to their potential risks for hypercalcaemia and hyperphosphataemia aggravation. Nevertheless, there is still a substantial clinical need to prevent the development of parathyroid gland autonomy, with its associated consequences of bone and vascular damage, including fracture risks and cardiovascular events. Therefore we now attempt to review the current guideline-based and clinical practice management of SHPT in ND-CKD, including their strengths and weaknesses, favouring individualised approaches respecting calcium and phosphate homeostasis. We further comment on extended-release calcifediol (ERC) as a new differential therapeutic option now also available in Europe and on a potentially novel understanding of a required vitamin D saturation in more advanced CKD stages. There is no doubt, however, that knowledge gaps will remain unless powerful randomised controlled trials with hard and meaningful endpoints are performed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of acute kidney injury (AKI) is also linked to the fact that this condition is often complicated by dysfunctions of other organs such as lungs or heart, or is associated with septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of fibroblast growth factor 23 and Klotho as a link between the bone-kidney-heart axis., Competing Interests: J.B. is member of the CKJ editorial board. The other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO 4 3- ), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO 4 3- in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO 4 3- on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO 4 3- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO 4 3- overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

While patient care, kidney replacement therapy, and transplantation techniques for chronic kidney disease (CKD) have continued to progress, the incidence of malnutrition disorders in CKD appears to have remained unchanged over time. However, there is now a better understanding of the underlying pathophysiology according to the disease background, disease stage, and the treatment received. In CKD patients, the increased production of proinflammatory cytokines and oxidative stress lead to a proinflammatory milieu that is at least partially responsible for the increased morbidity and mortality in this patient population. New insights into the pathogenic role of innate immunity and the proinflammatory cytokine profile, characterized, for instance, by higher levels of IL-6 and TNF-α, explain some of the clinical and laboratory abnormalities observed in these patients. In this article, we will explore currently available nutritional-inflammatory biomarkers in distinct CKD populations (hemodialysis, peritoneal dialysis, transplantation) with a view to evaluating their efficacy as predictors of malnutrition and their involvement in the common proinflammatory process. Although there is a direct relationship between inflammatory-nutritional status, signs and symptoms [e.g., protein-energy wasting (PEW), anorexia], and comorbidities (e.g., atheromatosis, atherosclerosis), we are in need of clearly standardized markers for nutritional-inflammatory assessment to improve their performance and design appropriate bidirectional interventions.

Point-of-Care Ultrasonography (PoCUS) aims to include a fifth pillar (insonation) in the classical physical examination in order to obtain images to answer specific questions by the clinician at the patient's bedside, allowing rapid identification of structural or functional abnormalities, enabling more accurate volume assessment and supporting diagnosis, as well as guiding procedures. In recent years, PoCUS has started becoming a valuable tool in day-to-day clinical practice, adopted by healthcare professionals from various medical specialties, never replacing physical examination but improving patient and medical care and experience. Renal patients represent a wide range of diseases, which lends PoCUS a special role as a valuable tool in different scenarios, not only for volume-related information but also for the assessment of a wide range of acute and chronic conditions, enhancing the sensitivity of conventional physical examination in nephrology. PoCUS in the hands of a nephrologist is a precision medicine tool., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K + ) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K + homeostasis, and we review the effects of dietary K + on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K + secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.

Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Secondary hyperparathyroidism (SHPT) is an integral component of the chronic kidney disease-mineral and bone disorder (CKD-MBD). Many factors have been associated with the development and progression of SHPT but the presence of skeletal or calcemic resistance to the action of PTH in CKD has often gone unnoticed. The term hyporesponsiveness to PTH is currently preferred and, in this chapter, we will not only review the scientific timeline but also some of the molecular mechanisms behind. Moreover, the presence of resistance to the biological action of PTH is not unique in CKD since resistance to other hormones has also been described ("uremia as a receptor disease"). This hyporesponsiveness carries out important clinical implications since it explains, at least partially, not only the progressive nature of the pathogenesis of CKD-related PTH hypersecretion and parathyroid hyperplasia but also the increasing prevalence of adynamic bone disease in the CKD population. Therefore, we underline the importance of PTH control in all CKD stages, but not aiming to completely normalize PTH levels since a certain degree of SHPT may represent an adaptive clinical response. Future studies at the molecular level, i.e. on uremia or the recent description of the calcium-sensing receptor as a phosphate sensor, may become of great value beyond their significance to explain just the hyporesponsiveness to PTH in CKD., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients., Methods: A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain., Results: The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival., Conclusions: Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.

Bisphenol A (BPA) is a compound that is especially widespread in most commonly used objects due to its multiple uses in the plastic industry. However, several data support the need to restrict its use. In recent years, new implications of BPA on the renal system have been discovered, which denotes the need to expand studies in patients. To this end, a systematic review and a meta-analysis was performed to explore existing literature that examines the BPA-kidney disease paradigm and to determine what and how future studies will need to be carried out. Our systematic review revealed that only few relevant publications have focused on the problem. However, the subsequent meta-analysis revealed that high blood concentrations of BPA could be a factor in developing kidney disease, at least in people with previous pathologies such as diabetes or hypertension. Furthermore, BPA could also represent a risk factor in healthy people whose urinary excretion is higher. Finally, the data analyzed from the NHANES 03-16 cohort provided new evidence on the possible involvement of BPA in kidney disease. Therefore, our results underline the need to carry out a thorough and methodologically homogeneous study, delving into the relationship between urinary and blood BPA, glomerular filtration rate, and urine albumin-to-creatinine ratio, preferably in population groups at risk, and subsequently in the general population, to solve this relevant conundrum with critical potential implications in Public Health.

Formaldehyde is a well-known toxic agent, therefore having a highly regulated status. Despite, some cosmetic firms recently introduced high and illegal concentrations of formaldehyde in hair treatments for increasing straightening and long-lasting performances. The objective of this study was to assess how and to which extent, these products may disperse formaldehyde in the environment of a hair salon, possibly exposing the consumer and the hair professional technician to hazardous airborne amounts of formaldehyde. A laboratory room was equipped with three air pumps located at three locations: close to the heads of a mannequin, nearby the hair technician and the whole volume of the room. Pumps were connected to cartridges apt at trapping airborne formaldehyde. The latter was further quantified through an HPLC procedure.As compared to hair treatments free from formaldehyde that do not modify the airborne formaldehyde levels, products with a high concentration of formaldehyde (1.7% and 9.3%) disperse this compound in the environment to a high and hazardous concentration, detrimental to both consumer and hair professional. The brushing procedure on the hair led to a much higher dispersion of airborne formaldehyde than the hair straightening/ironing technique. To conclude, the use of hair treatments that contain high and illegal amounts of formaldehyde creates a hazardous environment to all people present within a hair salon. Implications : This methodology adopted here might be used to evaluate during conception phase the level of Formaldehyde release and be used as part of safety data for the registration. However, the present work also strongly promotes the adoption of electronic detectors (commercially available) that continuously record the aerial concentration of Formaldehyde, when dealing with hair styling products that contain legal or illegal (> 0.2%w/w) content of Formaldehyde These detectors not only cover an adequate and realistic range of aerial Formaldehyde but can be used and transported at different locations of a given space. Such a cautious measure comes from common sense as it relates to the health status of consumers and operators present in a hair salon environment.

Background and Objectives: In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO., Design, Setting, Participants, & Measurements: Patients with coronary artery calcification at screening (Agatston score of 100-3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance., Results: Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were -1.5% (-2.7% to -0.3%), -1.5% (-2.7% to -0.4%), and -2.5% (-3.8% to -1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were -0.3% (-1.6% to 1.0%), -1.0% (-2.3% to 0.2%), and -2.6% (-4.0% to -1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively., Conclusions: Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups., Clinical Trial Registry Name and Registration Number: Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028., (Copyright © 2021 by the American Society of Nephrology.)

Although frequently silent, mineral and bone disease (MBD) is one of the most precocious complication of chronic kidney disease (CKD) and is omnipresent in patients with CKD stage 5. Its pathophysiology is complex, but basically, disturbances in vitamin D, phosphate, and calcium metabolism lead to a diverse range of clinical manifestations with secondary hyperparathyroidism usually being the most frequent. With the decline in renal function, CKD-MBD may induce microstructural changes in bone, vascular system and soft tissues, which results in macrostructural lesions, such as low bone mineral density (BMD) resulting in skeletal fractures, vascular and soft tissue calcifications. Moreover, low BMD, fractures, and vascular calcifications are linked with increased risk of cardiovascular mortality and all-cause mortality. Therefore, a better characterization of CKD-MBD patterns, beyond biochemical markers, is helpful to adapt therapies and monitor strategies as used in the general population. An in-depth characterization of bone health is required, which includes an evaluation of cortical and trabecular bone structure and density and the degree of bone remodeling through bone biomarkers. Standard radiological imaging is generally used for the diagnosis of fracture or pseudo-fractures, vascular calcifications and other features of CKD-MBD. However, bone fractures can also be diagnosed using computed tomography (CT) scan, magnetic resonance (MR) imaging and vertebral fracture assessment (VFA). Fracture risk can be predicted by bone densitometry using dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QTC) and peripheral quantitative computed tomography (pQTC), quantitative ultrasound (QUS) and most recently magnetic resonance micro-imaging. Quantitative methods to assess bone consistency and strength complete the study and adjust the clinical management when integrated with clinical factors. The aim of this review is to provide a brief and comprehensive update of imaging techniques available for the diagnosis, prevention, treatment and monitoring of CKD-MBD.

Abnormal bone metabolism is an integral part of the chronic kidney disease-mineral bone disorder (CKD-MBD). For several reasons, the difficult bone compartment was neglected for some time, but there has been renewed interest as a result of the conception of bone as a new endocrine organ, the increasing recognition of the cross-talk between bone and vessels, and, especially, the very high risk of osteoporotic fractures (and associated mortality) demonstrated in patients with CKD. Therefore, it has been acknowledged in different guidelines that action is needed in respect of fracture risk assessment and the diagnosis and treatment of osteoporosis in the context of CKD and CKD-MBD, even beyond renal osteodystrophy. These updated guidelines clearly underline the need to improve a non-invasive approach to these bone disorders in order to guide treatment decisions aimed at not only controlling CKD-MBD but also decreasing the risk of fracture. In this report, we review the current role of the most often clinically used or promising biochemical circulating biomarkers such as parathyroid hormone, alkaline phosphatases, and other biochemical markers of bone activity as alternatives to some aspects of bone histomorphometry. We also mention the potential role of classic and new imaging techniques for CKD patients. Information on many aspects is still scarce and heterogeneous, but many of us consider that it is indeed time for action, recognizing our definitely limited ability to base certain treatment decisions only on our current non-comprehensive knowledge.

Chronic kidney diseases (CKD) are associated with mineral and bone diseases (MBD), including pain, bone loss, and fractures. Bone fragility related to CKD includes the risk factors observed in osteoporosis in addition to those related to CKD, resulting in a higher risk of mortality related to fractures. Unawareness of such complications led to a poor management of fractures and a lack of preventive approaches. The current guidelines of the Kidney Disease Improving Global Outcomes (KDIGO) recommend the assessment of bone mineral density if results will impact treatment decision. In addition to bone density, circulating biomarkers of mineral, serum bone turnover markers, and imaging techniques are currently available to evaluate the fracture risk. The purpose of this review is to provide an overview of the epidemiology and pathogenesis of CKD-associated bone loss. The contribution of the current tools and other techniques in development are discussed. We here propose a current view of how to better predict bone fragility and the therapeutic options in CKD.

Background: Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced vitamin D signalling and hypocalcaemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers., Methods: A systematic literature search was performed in PubMed to identify relevant randomized control trials to be included in the meta-analysis. Fixed- and random-effects models were used to pool study-level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels., Results: Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/mL) and larger when compared with placebo/no treatment (pooled reduction: 49.7 pg/mL). NVD supplementation increased levels of 25-hydroxyvitamin D [25(OH)D] in both analyses (increase within NVD study arm: 20.6 ng/mL, increase versus placebo/no treatment: 26.9 ng/mL). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 were observed, NVD supplementation caused calcium levels to increase when compared with placebo/no treatment (increase: 0.23 mg/dL)., Conclusions: Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in non-dialysis-CKD patients with SHPT is limited., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The efficacy and safety of sucroferric oxyhydroxide (SO) have been reported in clinical trials. However, real-life data are scarce. This study presents data on the use, efficacy and safety of SO in real clinical practice., Methods: We performed a retrospective multicentre study, without any influence on the prescription decisions, that included 220 patients from 11 Spanish centres. Demographic, treatment, analytical and nutritional parameters and adherence, side effects and dropout rates were collected during 6 months., Results: SO was initiated due to inadequate control of serum phosphate (P) in 70% of participants and in 24.5% to reduce the number of tablets. Monotherapy with SO increased from 44% to 74.1%, with a reduction in the average daily number of sachets/tablets from six to two. Serum P decreased by 20% (4.6 ± 1.2 versus 5.8 ± 1.3 mg/dL; P < 0.001), with a significant reduction in intact parathyroid hormone levels (P < 0.01). The percentage of patients with adequate serum P control at threshold levels of 5 and 4.5 mg/dL increased by 45.4% and 35.9%, respectively. Serum ferritin was not modified, while the transferrin saturation index increased significantly (P = 0.04). Serum albumin and normalized protein catabolic rate, when normalized by serum P, increased, averaging 37% and 39%, respectively (P < 0.001). Adherent patients increased from 28.2% to 52.7%. Adverse effects were reported by 14.1% of participants, with abandonment of treatment in 9.5%., Conclusions: The use of SO in real-life results in better control of serum P, a reduction in the number of tablets and an improvement in therapeutic adherence. In addition, it may be beneficial with regards to secondary hyperparathyroidism and nutritional status., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)