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

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. 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.

Treatment of secondary hyperparathyroidism in non-dialysis CKD: an appraisal 2022s.

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.

Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial.

BACKGROUND: We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment. METHODS: NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250-1500 mg/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders. RESULTS: In the intention-to-treat population (NAMR: n = 539; placebo: n = 183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40 ± 1.55 versus 5.79 ± 1.37 mg/dl, P < .001) with a mean difference of -0.39 mg/dl [95% confidence interval (CI) -0.66 to -0.13], but was comparable between the groups at week 52 [mean difference -0.08 (95% CI -0.36-0.20)]. In the completer population (n = 358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR. CONCLUSIONS: NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation.

Mineral and bone metabolism markers and mortality in diabetic patients on haemodialysis.

BACKGROUND: Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS (Current management of secondary hyperparathyroidism: a multicentre observational study) analysis was to assess whether bone and mineral laboratory values [calcium, phosphorus and parathyroid hormone (PTH)] contribute to this risk. METHODS: COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres in 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed. RESULTS: There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (P = .011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (>9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients [1.53 (95% confidence interval 1.07-2.19) and 1.17 (95% confidence interval 0.91-1.52)]. No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (P = .2 and P = .059, respectively). CONCLUSION: The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of chronic kidney disease-mineral and bone disorders.

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Peritoneal Expression of SGLT-2, GLUT1, and GLUT3 in Peritoneal Dialysis Patients.

INTRODUCTION: In peritoneal dialysis (PD) patients, the peritoneal membrane is affected by glucose-based solutions used as peritoneal dialysate fluids. This exposure leads to changes of the membrane which may eventually culminate in fibrosis and method failure. In vitro or animal studies demonstrated that glucose transporters are upregulated upon exposure to these solutions. Expression studies of glucose transporters in human peritoneum have not been reported yet. METHODS: Expression of SGLT-2, GLUT1, and GLUT3 in human peritoneal biopsies was analyzed by real-time polymerase chain reaction and Western blot analysis. The localization of these glucose transporters in the peritoneum was evaluated by immunohistochemistry using a Histo-Score. RESULTS: Peritoneal biopsies of patients (healthy controls, uremic, PD, and encapsulating peritoneal sclerosis [EPS]) were analyzed. We found evidence of SGLT-2, GLUT1, and GLUT3 expression in the peritoneal membrane. Protein expression of SGLT-2 increases with PD duration and is significantly enhanced in EPS patients. All transporters were predominantly, but not exclusively, located adjacent to the vessel walls of the peritoneal membrane. CONCLUSION: Our study showed that SGLT-2, GLUT1, and GLUT3 were regularly expressed in the human peritoneum. SGLT-2 was particularly upregulated in PD patients with EPS, suggesting that this upregulation may be associated with pathological changes in the peritoneal membrane in this syndrome. Since preclinical studies in mice show that SGLT-2 inhibitors or downregulation of SGLT-2 ameliorated pathological changes in the peritoneum, SGLT-2 inhibitors may be potentially promising agents for therapy in PD patients that could reduce glucose absorption and delay functional deterioration of the peritoneal membrane in the long term.

Under-recognition of Acute Kidney Injury after Cardiac Surgery in the ICU Impedes Early Detection and Prevention.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality; therefore, prevention is important. The aim of this study was to systematically assess AKI incidence after cardiac surgery as documented in clinical routine compared to the real incidence because AKI may be under-recognized in clinical practice. Further, its postoperative management was compared to Kidney Disease: Improving Global Outcomes (KDIGO) recommendations because recognition and adequate treatment represent the fundamental cornerstone in the prevention and management of AKI. METHODS: This retrospective single-center study included n = 100 patients who underwent cardiac surgery with cardiopulmonary bypass. The coded incidence of postoperative AKI during intensive care unit stay after surgery was compared to the real AKI incidence. Furthermore, conformity of postoperative parameters with KDIGO recommendations for AKI prevention and management was reviewed. RESULTS: We found a considerable discrepancy between coded and real incidence, and conformity with KDIGO recommendations was found to be relatively low. The coded incidence was significantly lower (n = 12 vs. n = 52, p < 0.05), representing a coding rate of 23.1%. Regarding postoperative management, 90% of all patients had at least 1 episode with mean arterial pressure <65 mm Hg within the first 72 h. Furthermore, regarding other preventive parameters (avoiding hyperglycemia, stopping angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, avoiding contrast media, and nephrotoxic drugs), only 10 patients (20.8%) in the non-AKI group and in 5 (9.6%) subjects in the AKI group had none of all the above potential AKI-promoting factors. CONCLUSIONS: AKI recognition in everyday clinical routine seems to be low, especially in lower AKI stages, and the current postoperative management still offers potential for optimization. Possibly, higher AKI awareness and stricter postoperative management could already achieve significant effects in prevention and treatment of AKI.

The Role of Vitamin K in CKD-MBD.

PURPOSE OF REVIEW: We describe the mechanism of action of vitamin K, and its implication in cardiovascular disease, bone fractures, and inflammation to underline its protective role, especially in chronic kidney disease (CKD). RECENT FINDINGS: Vitamin K acts as a coenzyme of y-glutamyl carboxylase, transforming undercarboxylated in carboxylated vitamin K-dependent proteins. Furthermore, through the binding of the nuclear steroid and xenobiotic receptor, it activates the expression of genes that encode proteins involved in the maintenance of bone quality and bone remodeling. There are three main types of K vitamers: phylloquinone, menaquinones, and menadione. CKD patients, for several conditions typical of the disease, are characterized by lower levels of vitamin K than the general populations, with a resulting higher prevalence of bone fractures, vascular calcifications, and mortality. Therefore, the definition of vitamin K dosage is an important issue, potentially leading to reduced bone fractures and improved vascular calcifications in the general population and CKD patients.

Slowing Progression of Cardiovascular Calcification With SNF472 in Patients on Hemodialysis: Results of a Randomized Phase 2b Study.

BACKGROUND: The high cardiovascular morbidity and mortality in patients with end-stage kidney disease could be partially caused by extensive cardiovascular calcification. SNF472, intravenous myo-inositol hexaphosphate, selectively inhibits the formation and growth of hydroxyapatite. METHODS: This double-blind, placebo-controlled phase 2b trial compared progression of coronary artery calcium volume score and other measurements of cardiovascular calcification by computed tomography scan during 52 weeks of treatment with SNF472 or placebo, in addition to standard therapy, in adult patients with end-stage kidney disease receiving hemodialysis. Patients were randomized 1:1:1 to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions. The primary end point was change in log coronary artery calcium volume score from baseline to week 52. The primary efficacy analysis combined the SNF472 treatment groups and included all patients who received at least 1 dose of SNF472 or placebo and had an evaluable computed tomography scan after randomization. RESULTS: The mean change in coronary artery calcium volume score was 11% (95% CI, 7-15) for the combined SNF472 dose group and 20% (95% CI, 14-26) for the placebo group (P=0.016). SNF472 compared with placebo attenuated progression of calcium volume score in the aortic valve (14% [95% CI, 5-24] versus 98% [95% CI, 77-123]; P<0.001) but not in the thoracic aorta (23% [95% CI, 16-30] versus 28% [95% CI, 19-38]; P=0.40). Death occurred in 7 patients (4%) who received SNF472 and 5 patients (6%) who received placebo. At least 1 treatment-emergent adverse event occurred in 86%, 92%, and 87% of patients treated with SNF472 300 mg, SNF472 600 mg, and placebo, respectively. Most adverse events were mild. Adverse events resulted in discontinuation of SNF472 300 mg, SNF472 600 mg, and placebo for 14%, 29%, and 20% of patients, respectively. CONCLUSIONS: Compared with placebo, SNF472 significantly attenuated the progression of coronary artery calcium and aortic valve calcification in patients with end-stage kidney disease receiving hemodialysis in addition to standard care. Future studies are needed to determine the effects of SNF472 on cardiovascular events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02966028.

Old and New Drugs for the Management of Bone Disorders in CKD.

Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease (CKD), especially those undergoing dialysis. Renal osteodystrophy, which describes an alteration of bone morphology, is an important component of this systemic disorder and may explain the elevated risk of fracture which adversely affects morbidity and mortality. The most common form of renal osteodystrophy is high-turnover bone disease (osteitis fibrosa), which is induced by secondary hyperparathyroidism (SHPT). During the past decade, there has been considerable advances in the management of SHPT, with the introduction of the calcimimetic agents, the optimized use of nutritional and active vitamin D, and the accumulated experience with surgical parathyroidectomy. Studies supported that these advances could translate into improvement of renal bone disease and fracture prevention, as well as decreasing the risk of cardiovascular events and mortality. In this review, we summarize the available clinical evidence on the effect of old and new drugs on bone disorders in patients with CKD.

Iron kinetics following treatment with sucroferric oxyhydroxide or ferric citrate in healthy rats and models of anaemia, iron overload or inflammation.

BACKGROUND: The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models. METHODS: Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs. RESULTS: In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups. CONCLUSIONS: Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

Development of an International Standard Set of Value-Based Outcome Measures for Patients With Chronic Kidney Disease: A Report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD Working Group.

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care.

Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients.

BACKGROUND: Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate ('sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS: After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS: Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS: Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.

Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

BACKGROUND: The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. METHODS: In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD® on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low; T, target; H, high). We tested the association between CKD-MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score-adjusted proportional hazard regression. RESULTS: We enrolled 35 721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79; P < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18 014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). CONCLUSION: We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.

Children of a lesser god: exclusion of chronic kidney disease patients from clinical trials.

The exclusion of chronic kidney disease (CKD) patients from clinical trials-particularly cardiovascular trials-remains a long-standing, unsolved problem, which prevents the optimization of clinical care in these patients. The situation recalls the insufficient recruitment of women in cardiovascular trials until the 1980s, a problem that was only resolved following regulatory interventions. Regulatory agencies are in a unique position to promote recruitment of CKD patients in clinical trials. The main stakeholders, namely patients' associations and scientific societies, should make major lobbying efforts to persuade these agencies that the issue is an absolute public health priority.

Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study.

BACKGROUND: Serum phosphate is a key parameter in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). The timing of phosphate measurement is not standardized in the current guidelines. Since the optimal range of these biomarkers may vary depending on the duration of the interdialytic interval, in this analysis of the Current management of secondary hyperparathyroidism: a multicentre observational study (COSMOS), we assessed the influence of a 2- (midweek) or 3-day (post-weekend) dialysis interval for blood withdrawal on serum levels of CKD-MBD biomarkers and their association with mortality risk. METHODS: The COSMOS cohort (6797 patients, CKD Stage 5D) was divided into two groups depending upon midweek or post-weekend blood collection. Univariate and multivariate Cox's models adjusted hazard ratios (HRs) by demographics and comorbidities, treatments and biochemical parameters from a patient/centre database collected at baseline and every 6 months for 3 years. RESULTS: There were no differences in serum calcium or parathyroid hormone levels between midweek and post-weekend patients. However, in post-weekend patients, the mean serum phosphate levels were higher compared with midweek patients (5.5 ± 1.4 versus 5.2 ± 1.4 mg/dL, P < 0.001). Also, the range of serum phosphate with the lowest mortality risk [HR ≤ 1.1; midweek: 3.5-4.9 mg/dL (95% confidence interval, CI: 2.9-5.2 mg/dL); post-weekend: 3.8-5.7 mg/dL (95% CI: 3.0-6.4 mg/dL)] showed significant differences in the upper limit (P = 0.021). CONCLUSION: Midweek and post-weekend serum phosphate levels and their target ranges associated with the lowest mortality risk differ. Thus, clinical guidelines should consider the timing of blood withdrawal when recommending optimal target ranges for serum phosphate and therapeutic strategies for phosphate control.

Needs Around Dialysis Treatment from Different Perspectives (NADIP): Results of the Exploratory German Multicenter Survey.

BACKGROUND/AIMS: In 2015, approximately 70,000 patients with end-stage renal disease were treated chronically with dialysis in Germany. However, there is only sparse information regarding subjective appreciation of the different aspects of extracorporeal renal replacement therapies. This study was performed to gain insight into the needs and appreciation of services in dialysis centers in Germany including the views not only of the patients but also of the caregivers, physicians, and nurses. METHODS: A cross-sectional written voluntary questionnaire survey based on the international RAND Kidney Disease Quality of Life Short Form (version 1.3) comprising 510 adult dialysis patients, 274 caregivers, 29 physicians, and 60 nurses in 30 dialysis centers across Germany. RESULTS: Although patients were mostly satisfied with present treatment options, room for improvement exists. Patients were less critical of services than doctors and nurses. Factors such as trustworthy contact with staff at the centers as well as information exchange with other patients and among caregivers play a significant role in the patients' perception of a high-quality dialysis treatment facility. Therefore, continued cost saving, in particular regarding personnel, may subjectively counteract the objective technical improvements of dialysis. CONCLUSIONS: High-quality technical standards are essential for successful dialysis therapy; however, additionally, we recommend an array of communicative and social tools employed by all stakeholders to convey and exchange information and also support subjective well-being. This survey represents one of the largest evaluations to date. The data are also of potential international relevance for non-German health management systems.

Real-world study: Escalating targeted lipid-lowering treatment with PCSK9-inhibitors and lipoprotein apheresis.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid-lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long-term LA. PATIENTS AND METHODS: In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)-hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. RESULTS: Mean LDL-C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk-adjusted LDL-C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL-C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). CONCLUSION: Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real-world study. The termination of long-term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL-C reduction.

Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis. Methods: Development of the guideline update followed an explicit process of evidence review and appraisal. The approach adopted by the Work Group and the evidence review team was based on systematic reviews of relevant trials, appraisal of the quality of the evidence, and rating of the strength of recommendations according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Searches of the English-language literature were conducted through September 2015 and were supplemented with targeted searches through February 2017. Final modification of the guidelines was informed by a public review process involving numerous stakeholders, including patients, subject matter experts, and industry and national organizations. Recommendations: The update process resulted in the revision of 15 recommendations. This synopsis focuses primarily on recommendations for diagnosis of and testing for CKD-MBD and treatment of CKD-MBD that emphasizes decreasing phosphate levels, maintaining calcium levels, and addressing elevated parathyroid hormone levels in adults with CKD stage G3a to G5 and those receiving dialysis. Key elements include basing treatment on trends in laboratory values rather than a single abnormal result and being cautious to avoid hypercalcemia when treating secondary hyperparathyroidism.

The ERA-EDTA today and tomorrow: a progress document by the ERA-EDTA Council.

Scientific societies are increasingly seen as central to the advancement of information sharing and collaboration among scientists and clinical investigators for the progress of medical research and the promotion of education, professional competence, integrity and quality studies. To more effectively serve the practicing nephrologists and investigators dedicated to renal science, the Council of the European Renal Association and European Dialysis and Transplantation Association (ERA-EDTA) reorganized and integrated the various activities of the society into two branches, the Clinical Nephrology Governance branch and the Renal Science branch. New affordable initiatives to promote research, education and professional development and to advocate for the recognition of chronic kidney disease as a major public health issue at the European level will be put in place and/or potentiated in the new organizational frame. Educational initiatives will be espoused to Continuous Professional Development and, starting from 2019, 14 Education & Continuous Professional Development courses will be held covering the full range of knowledge areas of modern nephrology. Consolidation and development is the short- and medium-term mantra of the ERA-EDTA. The society has a rich portfolio of successful activities and brilliant, creative scientists among its members. Integrating the various activities of the ERA-EDTA and treasuring the expertise and wisdom of its most accomplished members will facilitate collaborative research, education and its public impact at large.