Skeletal fragility has long been overlooked by the nephrology community despite patients with chronic kidney disease (CKD) facing double the risk of hip fracture compared with the general population. Consequently, the term CKD-associated osteoporosis was recently coined to increase awareness. In this context, vertebral fractures are even less studied. Vertebral fractures predict increased fracture risk, and especially in advanced CKD, show a strong association with aortic and iliac vascular calcifications and cardiovascular events such as myocardial infarction. The scope of the present consensus paper is to comprehensively discuss the management of skeletal fragility in CKD patients, from diagnosis to treatment, with a particular focus on vertebral fractures in CKD G4-G5D.

Introduction: Glucocorticoid (GC)-sparing treatment strategies, such as the C5a receptor antagonist avacopan, could potentially replace the need for long-term GC therapy in ANCA-associated vasculitis (AAV). Therefore, an assessment of GC-related morbidity is required to provide justification for such therapies. The aim of this study was to assess the incidence and management of common GC-related adverse events. Methods: In this single-center cohort study, medical records were screened for patients with a diagnosis of AAV admitted to the Robert Bosch Hospital (RBK) in Stuttgart, Germany. A total of 74 patients admitted for treatment of AAV between 2004 and 2023 were included. We assessed the dosage and duration of GC therapy used to treat AAV, as well as the incidence of new-onset and worsening arterial hypertension and diabetes mellitus, using over 150,000 individual medication time points for calculation of GC therapy. Additionally, incidence of infections and fractures was recorded. Results: Including relapses, 127 vasculitis events were observed during a median follow-up time of 8.3 years (IQR 5.3-10.6). Median duration of glucocorticoid therapy was 2.9 years (IQR 1.3-5.8). Regarding adverse events, 15 patients (20%) developed new-onset diabetes mellitus and a significantly higher cumulative GC dose was observed in patients requiring insulin therapy compared with those on oral antidiabetics (p = 0.02). Furthermore, 38 (51%) patients were diagnosed with new-onset arterial hypertension. Patients requiring escalation of antihypertensive therapy had significantly higher cumulative GC dose after a vasculitis event (p = 0.0001). A total of 325 infectious events occurred across 69 patients (93%) during follow-up, mostly requiring (85%; n = 277) hospital admission. Cumulative GC dose was significantly higher in patients with documented infections (p = 0.002). Conclusions: GC-related adverse events are common in patients with AAV. This study provides evidence on the incidence of presumably treatment-related harms in AAV and further promotes the importance of reduced-dose or even GC-free treatment approaches.

Bone turnover abnormalities are common in chronic kidney disease (CKD) and contribute to bone fragility. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) introduced the term CKD-associated osteoporosis to describe bone fragility in CKD and highlighted the role of bone turnover markers (BTM) in clinical evaluation and management of bone fragility. However, current clinical practice guidelines lack specific treatment targets for bone turnover in the setting of CKD. The aim of this consensus was to present recommendations for the use of BTM in the management of CKD-associated osteoporosis. The consensus was conducted by members of relevant working groups of the European Renal Association (ERA), International Osteoporosis Foundation (IOF), European Foundation for Clinical Chemistry and Laboratory Medicine (EFLM) and European Society of Pediatric Nephrology (ESPN). Bone-specific alkaline phosphatase and tartrate resistant acid phosphatase isoform 5b are not renally cleared and considered reliable diagnostic tools for bone evaluation in CKD-associated osteoporosis. Both have been proposed as reference BTM in CKD by a recent international consortium. Intact N-terminal telopeptide of type I collagen can also be used in CKD. The current consensus describes methodological considerations and the clinical usefulness of BTM in risk prediction, choice of therapeutic strategy, and treatment evaluation in CKD-associated osteoporosis. Specific diagnostic ranges for bone turnover abnormalities are provided. Future research should focus on the integration of these reference BTM with other diagnostic tools, establishment of concrete treatment targets, and development of treatment strategies to reach these targets.

OBJECTIVES:The aim of this study was to determine the differential dose response of parathyroid hormone (PTH) and fibroblast growth factor (FGF23) to paricalcitol in patients with secondary hyperparathyroidism and end-stage renal failure on chronic intermittent hemodialysis. MATERIALS AND METHODS:The multicenter, randomized, double-blind, prospective, crossover study comprised a total of 43 hemodialysis patients (average age 64 years, female 30%) with 31 complete patient data sets, and with PTH levels between 200 and 600 pg/mL, serum calcium < 2.55 mmol/L, phosphorus ≤ 2.1 mmol/L, and 25 OH-vitamin D > 20 ng/mL as inclusion criteria (Eudract 2007-006606-16). RESULTS:Mean intact PTH at baseline was 319 pg/mL (standard deviation (SD) 141, normal 11.3 - 42.4 pg/mL; ECLIA; Roche, Basel, Switzerland) and FGF23 651.25 RU/mL (SD 1,099.98; normal 21 - 424 RU/mL; c-terminal, 2nd generation ELISA kit, Immutopics, San Clemente, CA, USA) at baseline. The initial oral dose of paricalcitol was 2 μg/day, adjusted to a mean dosage of 1.9 μg/day at week 6 and 1.5 μg/day at week 12, guided by PTH response. PTH levels remained significantly suppressed at both 6 (189 pg/mL; SD 95) and 12 weeks (164 pg/mL; SD 95), both p < 0.001 as compared to baseline. FGF23 levels showed a significant increase at 6 weeks (1,442.1 RU/mL, SD 1,860.2; p = 0.002) but returned at 12 weeks to levels not significantly different from baseline (1,150.7 RU/mL, SD 1,509.3; p = 0.24). CONCLUSION:Treatment with paricalcitol resulted in a significant reduction in PTH levels at both 6 and 12 weeks compared to placebo. The suppression of PTH levels with paricalcitol was possible without elevating FGF23 within the restrictions of this short duration study, at least if over-suppression of PTH is avoided by dose adaption. Our findings suggest a cautious lower oral paricalcitol starting dose to mitigate the initial spike in FGF23 while effectively managing PTH levels.

In 2017, Kidney Disease: Improving Global Outcomes (KDIGO) published a Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Since then, new lines of evidence have been published related to evaluating disordered mineral metabolism and bone quality and turnover, identifying and inhibiting vascular calcification, targeting vitamin D levels, and regulating parathyroid hormone. For an in-depth consideration of the new insights, in October 2023, KDIGO held a Controversies Conference on CKD-MBD: Progress and Knowledge Gaps Toward Personalizing Care. Participants concluded that the recommendations in the 2017 CKD-MBD guideline remained largely consistent with the available evidence. However, the framework of the 2017 Guideline, with 3 major sections-biochemical abnormalities in mineral metabolism; bone disease; and vascular calcification-may no longer best reflect currently available evidence related to diagnosis and treatment. Instead, future guideline efforts could consider mineral homeostasis and deranged endocrine systems in adults within a context of 2 clinical syndromes: CKD-associated osteoporosis, encompassing increased fracture risk in patients with CKD; and CKD-associated cardiovascular disease, including vascular calcification and structural abnormalities, such as valvular calcification and left ventricular hypertrophy. Participants emphasized that the complexity of bone and cardiovascular manifestations of CKD-MBD necessitates personalized approaches to management.

Secondary hyperparathyroidism (sHPT) is in the beginning an adaptive reaction and later often a maladaptive complication of chronic progressive renal dysfunction up to the dialysis stage. The sHPT is primarily triggered by a suppressed renal vitamin D activation, subsequent hypocalcemia and hyperphosphatemia. A disproportionally increased bone turnover and progressive bone resorption increase the fracture risk of affected patients. The preventive treatment of patients with chronic kidney disease (CKD) specifically aims at a stage-directed restoration of vitamin D availability in CKD stages 3-5; however, always considering the calcium and phosphate serum levels. In the dialysis stage (CKD stage 5D), calcimimetics represent an additional and effective treatment option. The aims of treatment are maintenance of a normal bone turnover and avoidance of uncontrolled electrolyte disturbances, such as hypercalcemia and hyperphosphatemia, which may in turn cause cardiovascular risks.

The number of older people with CKD is globally increasing. The vast majority of these patients will die before they even have the chance to start kidney replacement therapy. Nevertheless, this clientele of older patients with CKD is often characterized not only by several concomitant diseases but also by frailty. This constellation comes with a general vulnerability and very heterogeneous courses of disease that need to be considered when it comes to diagnosis and treatment. The main difference to younger patients is that therapy and therapy decisions are often preceded by the need for assessments. These can relate to frailty, but also to closely related areas such as cognition, depression or malnutrition among others. The basic therapeutic approaches for CKD treatment in a geriatric patient may not differ fundamentally though from those for younger patients. This also holds true for standard as well as more novel medication administered for nephroprotection. The difference however, lies in the fact that personalized approaches are more frequently required due to survival probability, a more complex mix of chronic conditions, and individual patient's needs and aims. This also applies to the difficult decision as to whether a very old person with CKD G5 should be dialyzed or treated conservatively. Information from different areas should be incorporated into a joint decision-making process, which often requires intensive, patient-centered communication about the patient's preferences and prioritized treatment goals, psychosocial factors and their home environment, as well as their medical needs and prognosis.

Der sekundäre Hyperparathyreoidismus (sHPT) ist eine anfangs adaptive Reaktion, im Verlauf häufig maladaptive Komplikation chronisch fortschreitender Nierenfunktionsstörungen bis in das Dialysestadium hinein. Der sHPT wird in erster Linie getriggert durch die verminderte renale Vitamin-D-Aktivierung, konsekutive Hypokalzämien und Hyperphosphatämie. Ein dysproportional erhöhter Knochenumsatz und progressiver Knochenabbau erhöhen das Frakturrisiko betroffener Patient*innen. Die präventive Behandlung bei Patient*innen mit chronischer Nierenkrankheit („chronic kidney disease“, CKD) in den CKD-Stadien 3 bis 5 zielt auf eine stadiengerechte Rekonstitution der Vitamin-D-Verfügbarkeit ab, allerdings unter Beachtung der Serumkonzentrationen von Kalzium und Phosphat. Im Dialysestadium (CKD-Stadium 5D) kommen zusätzlich Kalzimimetika zum Einsatz. Ziele der Therapie sind die Aufrechterhaltung eines normalen Knochenumbaus und die Vermeidung von unkontrollierten Elektrolytstörungen wie Hyperkalzämien und Hyperphosphatämien, die wiederum kardiovaskuläre Risiken nach sich ziehen.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia, reduced active vitamin D (1,25-OH2 vitamin D), and hypercalciuria. Due to its rarity, non-specialized physicians often lack experience managing HypoPT. To address this, expert consensus statements were developed for the DACH region (Germany, Austria, Switzerland), considering regional differences and high HypoPT incidence. These statements aim to enhance adherence to guideline recommendations and improve non-specialist knowledge. From December 2023 to April 2024, three rounds of a Delphi consensus survey were conducted with seven DACH-region clinical experts. Consensus was defined as agreement among at least 6 of 7 participants (85

Calciphylaxis, or calcific uraemic arteriolopathy, is a rare and life-threatening condition predominantly affecting people receiving dialysis. Characterized by painful necrotic skin lesions due to arteriolar calcification and thrombosis, calciphylaxis is associated with high morbidity and mortality. Diagnosis is frequently delayed due to misdiagnosis and an absence of specific diagnostic tests. Current treatment approaches are largely based on registry data and small uncontrolled studies. This update brings together the latest understanding of calciphylaxis pathogenesis, diagnostic approaches and management, highlighting recent advances and future directions. Pathophysiological mechanisms include vascular smooth muscle cell osteogenic transformation, loss of endogenous calcification inhibitors (fetuin-A, matrix Gla protein, pyrophosphate), systemic inflammation and thrombosis. The potential prognostic role of biomarkers, including the calciprotein particle crystallization test (T50) and plasma pyrophosphate, are also discussed. Management remains complex, with no proven treatments. A multifaceted, and multi-professional team approach is fundamental. Sodium thiosulfate remains widely used despite the lack of trial evidence. Recent investigational therapies, including SNF472 and INZ-701, target key calcification pathways and offer promise. The Better Evidence and Translation for Calciphylaxis (BEAT-Calci) adaptive platform trial represents a landmark step in evaluating multiple therapies systematically. National registries remain vital for informing prevalence estimates and improving real-world outcome data. Looking ahead, future research should prioritize the development and validation of diagnostic criteria, and prognostic tools integrating clinical risk factors with biomarkers. In addition, we propose the routine inclusion of patient-reported experience measures in calciphylaxis studies to better capture treatment impact in this vulnerable population.

ZUSAMMENFASSUNGIm Jahr 2017 wurde das letzte Update der Leitlinien zu den Störungen des Mineral- und Knochenhaushalts bei chronischen Nierenkrankheiten (CKD-MBD: „chronic kidney disease – mineral and bone disorders“) der Initiative KDIGO (Kidney Disease: Improving Global Outcomes) publiziert. Seitdem haben sich neue Erkenntnisse zu Themen wie Knochenqualität und -umsatz im Kontext der Osteoporose, dem Umgang mit progressiven Gefäßverkalkungen, der Einschätzung des Vitamin-D-Status und der Regulation des Parathormons (PTH) ergeben. Dieser Übersichtsartikel benennt exemplarisch diese teilweise neuen Einschätzungen und stellt potenzielle Auswirkungen auf zukünftige diagnostische und therapeutische Verfahrensweisen dar.

The KDIGO Update 2024 was supplemented by new "Clinical Practice Points", which were derived from the current evidence but are not necessarily comprehensively proven by prospective controlled studies. The most significant change in the Update 2024 for Lupus nephritis concerns the recommendations for induction therapy for lupus nephritis classes III and IV. The basis is still high-dose glucocorticoid treatment and the use of hydroxychloroquine. The 2 new developments in the 2024 Update concerning ANCA-associated nephritis are based on the studies on the use of the C5a receptor inhibitor Avacopan and the increasing data on induction protocols with reduced glucocorticoid dosage. Due to the inconsistency and variability of the conditions under which blood pressure measurements are carried out in practice, an international consensus statement was issued which defines 4 steps to achieve sufficient validity of the measurement results. CKD-MBD Controversies Conference 2023: The update for CKD-MBD, which was discussed in the Controversies Conference 2023, is in progress and has not been released yet. However, there were no serious contradictions between the 2023 data and the 2017 guidelines - the risk assessment regarding calcium-containing phosphate binders may have been put into perspective.

Kalzium ist elementar fur zahlreiche Stoffwechselprozesse und wird hormonell gesteuert. Diese hormonellen Mechanismen sind erstaunlich effektiv, die Kalziumwerte sehr zuverlassig in einem engen Bereich zu regulieren - dennoch verursachen Abweichungen der Serumkalziumwerte recht haufig klinische Probleme, deren Ursachen, Diagnostik und Therapie in diesem Dossier weiter erortert werden sollen. Abstract Calcium is essential for numerous metabolic processes and is hormonally controlled. These hormonal mechanisms are surprisingly effective in regulating calcium levels very reliably within a narrow range - but deviations in serum calcium levels quite often cause clinical problems. Hypercalcemia predominantly occurs in primary hyperparathyroidism or is associated with tumors (especially osteolytic processes). Hypocalcemia is usually due to hypoparathyroidism (75% surgical, 25% primary) or vitamin D deficiency. Causal calcium management requires identification of the etiology of the disorder. Symptomatic therapy depends on the severity of the electrolyte imbalance. Calcium is lowered in hypercalcemia via forced diuresis, the administration of calcitonin and bisphosphonates or denosumab, if necessary, via dialysis. Severe hypocalcemia is corrected acutely with parenteral calcium administration and any further treatment decisions and prognosis depend on the underlying disease.

BACKGROUND:Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of chronic kidney disease-mineral and bone disorders (CKD-MBD) and bone fragility fractures in the COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) project. METHODS:COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 haemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and parathyroid hormone (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 {hazard ratio (HR) 1.53 [95% confidence interval (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 haemodialysis patients.

Kalzium ist elementar für zahlreiche Stoffwechselprozesse und wird hormonell gesteuert. Diese hormonellen Mechanismen sind erstaunlich effektiv, die Kalziumwerte sehr zuverlässig in einem engen Bereich zu regulieren – dennoch verursachen Abweichungen der Serumkalziumwerte recht häufig klinische Probleme, deren Ursachen, Diagnostik und Therapie in diesem Dossier weiter erörtert werden sollen.

ABSTRACT 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.