RESUMEN

AIMS: Fear of physical activity (PA) is discussed as a barrier to regular exercise in patients with heart failure (HF), but HF-specific theoretical concepts are lacking. This study examined associations of fear of PA, heart-focused anxiety and trait anxiety with clinical characteristics and self-reported PA in outpatients with chronic HF. It was also investigated whether personality-related coping styles for dealing with health threats impact fear of PA via symptom perception. METHODS AND RESULTS: This cross-sectional study enrolled 185 HF outpatients from five hospitals (mean age 62 ± 11 years, mean ejection fraction 36.0 ± 12%, 24% women). Avoidance of PA, sports/exercise participation (yes/no) and the psychological characteristics were assessed by self-reports. Fear of PA was assessed by the Fear of Activity in Situations-Heart Failure (FActS-HF15) questionnaire. In multivariable regression analyses higher NYHA class (b = 0.26, p = 0.036) and a higher number of HF drugs including antidepressants (b = 0.25, p = 0.017) were independently associated with higher fear of PA, but not with heart-focused fear and trait anxiety. Of the three anxiety scores only increased fear of PA was independently associated with more avoidance behavior regarding PA (b = 0.45, SE = 0.06, p < 0.001) and with increased odds of no sports/exercise participation (OR = 1.34, 95% CI 1.03-1.74, p = 0.028). Attention towards cardiac symptoms and symptom distress were positively associated with fear of PA (p < 0.001), which explained higher fear of PA in patients with a vigilant (directing attention towards health threats) coping style (p = 0.004). CONCLUSIONS: Fear of PA assessed by the FActS-HF15 is a specific type of anxiety in patients with HF. Attention towards and being distressed by HF symptoms appear to play a central role in fear of PA, particularly in vigilant patients who are used to direct their attention towards health threats. These findings provide approaches for tailored interventions to reduce fear of PA and to increase PA in patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02898246.

Asunto(s)

Adaptación Psicológica , Ejercicio Físico , Miedo , Insuficiencia Cardíaca , Autoinforme , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ansiedad/psicología , Enfermedad Crónica , Estudios Transversales , Ejercicio Físico/psicología , Miedo/psicología , Insuficiencia Cardíaca/psicología , Insuficiencia Cardíaca/fisiopatología , Encuestas y Cuestionarios

RESUMEN

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.

Asunto(s)

Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Proteínas de la Matriz Extracelular/sangre , Precursores de Proteínas/sangre , Calcificación Vascular/sangre , Deficiencia de Vitamina K/sangre , Vitamina K/sangre , 4-Hidroxicumarinas/uso terapéutico , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/complicaciones , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Suplementos Dietéticos , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Indenos/uso terapéutico , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Estado Nutricional , Protrombina , Diálisis Renal/efectos adversos , Uremia/sangre , Uremia/complicaciones , Calcificación Vascular/complicaciones , Vitamina K/antagonistas & inhibidores , Vitamina K/uso terapéutico , Deficiencia de Vitamina K/complicaciones , Proteína Gla de la Matriz

RESUMEN

BACKGROUND AND PURPOSE: No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated. EXPERIMENTAL APPROACH: We examined SNF472 binding features (affinity, release kinetics and antagonism type) for HAP crystals in vitro, inhibition of calcification in excised vascular smooth muscle cells from rats and bone parameters in osteoblasts from dogs and rats. KEY RESULTS: SNF472 bound to HAP with affinity (KD ) of 1-10 µM and saturated HAP at 7.6 µM. SNF472 binding was fast (80% within 5 min) and insurmountable. SNF472 inhibited HAP crystal formation from 3.8 µM, with complete inhibition at 30.4 µM. SNF472 chelated free calcium with an EC50 of 539 µM. Chelation of free calcium was imperceptible for SNF472 1-10 µM in physiological calcium concentrations. The lowest concentration tested in vascular smooth muscle cells, 1 µM inhibited calcification by 67%. SNF472 showed no deleterious effects on bone mineralization in dogs or in rat osteoblasts. CONCLUSION AND IMPLICATIONS: These experiments show that SNF472 binds to HAP and inhibits further HAP crystallization. The EC50 for chelation of free calcium is 50-fold greater than a maximally effective SNF472 dose, supporting the selectivity of SNF472 for HAP. These findings indicate that SNF472 may have a future role in the treatment of vascular calcification and calcific uraemic arteriolopathy in patients undergoing dialysis.

Asunto(s)

Calcifilaxia , Calcificación Vascular , Animales , Calcifilaxia/tratamiento farmacológico , Perros , Humanos , Ácido Fítico , Ratas , Diálisis Renal , Calcificación Vascular/tratamiento farmacológico

RESUMEN

AIM: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF. CONCLUSIONS: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation.

Asunto(s)

Factores de Crecimiento de Fibroblastos/análisis , Insuficiencia Cardíaca , Anciano , Factor-23 de Crecimiento de Fibroblastos , Humanos , Persona de Mediana Edad , Pronóstico , Volumen Sistólico , Función Ventricular Izquierda

RESUMEN

Accelerated and premature cardiovascular calcification is a hallmark of patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). The presence and the amount of cardiovascular calcification are among the driving forces of increased morbidity and mortality in renal patients. Cardiovascular calcification occurs at different sites, including the cardiac valves-a location that is of particular importance for both the patient and the treating physician. The correlation between degree of calcification and functional impairment is particularly close at the aortic valve, that is, the amount of calcification predicts the degree of stenosis. Calcific aortic stenosis (CAS) is the most prevalent valvular heart disease in Western societies. CAS is particularly prevalent in patients with underlying CKD or ESRD. CAS increases afterload and hence contributes to the widespread finding of left ventricular hypertrophy in CKD/ESRD patients. Medical treatment options to prevent the development and progression of CAS are limited. Hence, close surveillance and timely referral of patients for heart valve replacement therapy is a mainstay of current therapy. Novel treatment approaches, such as transcatheter aortic valve implantation, offer promising yet challenging options for elderly, comorbid, and often frail patients with CAS in combination with advanced CKD/ESRD.

Asunto(s)

Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/patología , Calcinosis/tratamiento farmacológico , Calcinosis/cirugía , Insuficiencia Renal Crónica/complicaciones , Vitamina K/uso terapéutico , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/etiología , Calcinosis/etiología , Hormonas y Agentes Reguladores de Calcio/uso terapéutico , Quelantes/uso terapéutico , Cinacalcet/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Sevelamer/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter , Vitamina K/antagonistas & inhibidores

RESUMEN

BACKGROUND: Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification. METHODS: In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations. RESULTS: Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related. CONCLUSIONS: SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.

Asunto(s)

Calcifilaxia/tratamiento farmacológico , Dolor/tratamiento farmacológico , Ácido Fítico/administración & dosificación , Calidad de Vida , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Fítico/farmacología , Estudios Prospectivos , Factores de Tiempo

RESUMEN

Canonical Wnt signalling activity is a major player in physiological and adaptive bone metabolism. Wnt signalling is regulated by soluble inhibitors, with sclerostin being the most widely studied. Sclerostin's main origin is the osteocyte and its major function is blockade of osteoblast differentiation and function. Therefore, sclerostin is a potent inhibitor of bone formation and mineralization. Consequently, blocking sclerostin via human monoclonal antibodies (such as romosozumab) represents a promising perspective for the treatment of (postmenopausal) osteoporosis. However, sclerostin's physiology and the effects of sclerostin monoclonal antibody treatment are not limited to the skeleton. Specifically, the potential roles of sclerostin in chronic kidney disease (CKD) and associated pathologies covered by the term chronic kidney disease and mineral bone disorder (CKD-MBD), which also includes accelerated cardiovascular calcification, warrant specific attention. CKD-MBD is a complex disease condition in which sclerostin antibodies may interfere at different levels and influence the multiform interplay of hyperparathyroidism, renal osteodystrophy and vascular calcification, but the clinical sequelae remain obscure. The present review summarizes the potential effects of sclerostin blockade in CKD-MBD. We will address and summarize the urgent research targets that are being identified and that need to be addressed before a valid risk-benefit ratio can be established in the clinical setting of CKD.

Asunto(s)

Enfermedades Óseas/tratamiento farmacológico , Proteínas Morfogenéticas Óseas/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/tratamiento farmacológico , Calcificación Vascular/inducido químicamente , Proteínas Adaptadoras Transductoras de Señales , Marcadores Genéticos , Humanos , Pronóstico

Asunto(s)

Calcifilaxia , Humanos

Asunto(s)

Calcifilaxia , Edad de Inicio , Calcifilaxia/diagnóstico , Calcifilaxia/etiología , Calcifilaxia/patología , Calcifilaxia/terapia , Desbridamiento , Diagnóstico Diferencial , Humanos , Enfermedades Renales/complicaciones , Microvasos/patología , Pronóstico , Factores de Riesgo , Tiosulfatos/uso terapéutico , Vitamina K 1/uso terapéutico

RESUMEN

PURPOSE: Fear of physical activity (FoPA) has been suggested as a psychological barrier to exercise-based cardiac rehabilitation and everyday physical activity (PA) in patients with heart failure (HF). We evaluated the recently developed Fear of Activity in Situations-Heart Failure (FActS-HF) questionnaire that assesses affective/cognitive fear reactions to situations of varying PA intensities. METHODS: The FActS-HF was given to 132 ambulatory patients with stable HF (67 ± 12 years, 80% men). In 121 participants with valid FActS-HF data, the questionnaire's dimensionality was investigated. Psychometric properties were determined in terms of reliability and validity. We assessed convergent and discriminant correlations of FoPA with anxiety, kinesiophobia, and depression. External validation criteria encompassed clinical variables and objectively assessed accelerometer measures of everyday PA in a subsample of 61 participants. RESULTS: The FActS-HF measures a unidimensional construct (i.e., FoPA) based on items presenting varying PA intensities (i.e., the more intense the PA, the stronger the fear response). The scale demonstrated good 2-week stability (r tt = 0.82) and excellent internal consistency reliability (α = 0.97). FoPA was moderately to strongly associated with anxiety and kinesiophobia, and weakly to moderately associated with state/trait depression, supporting convergent and discriminant validity, respectively. High FoPA was associated with feeling uninformed about HF, comorbidities, non participitation to cardio fitness groups, and less stair climbing, as measured by accelerometry. CONCLUSION: The FActS-HF is a reliable and valid instrument to measure FoPA in patients with HF and provides a promising tool for further research and practice.

Asunto(s)

Ejercicio Físico/psicología , Miedo/psicología , Insuficiencia Cardíaca/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados

RESUMEN

Sclerostin is a soluble antagonist of canonical Wnt signaling and a strong inhibitor of bone formation. We present experimental data on the role of sclerostin in chronic kidney disease - bone mineral disorder (CKD-MBD). METHODS: We performed 5/6 nephrectomies in 36-week-old sclerostin-deficient (SOST-/-) B6-mice and in C57BL/6J wildtype (WT) mice. Animals received a high phosphate diet for 11weeks. The bones were analyzed by high-resolution micro-computed tomography (µCT) and quantitative bone histomorphometry. Aortic tissue was analyzed regarding the extent of vascular calcification. RESULTS: All nephrectomized mice had severe renal failure, and parathyroid hormone was highly increased compared to corresponding sham animals. All SOST-/- animals revealed the expected high bone mass phenotype. Overall, the bone compartment in WT and SOST-/- mice responded similarly to nephrectomy. In uremic WT animals, µCT data at both the distal femur and lumbar spine revealed significantly increased trabecular volume compared to non-uremic WTs. In SOST-/- mice, the differences between trabecular bone volume were less pronounced when comparing uremic with sham animals. Cortical thickness and cortical bone density at the distal femur decreased significantly and comparably in both genotypes after 5/6 nephrectomy compared to sham animals (cortical bone density -18% and cortical thickness -32%). Overall, 5/6 nephrectomy and concomitant hyperparathyroidism led to a genotype-independent loss of cortical bone volume and density. Overt vascular calcification was not detectable in either of the genotypes. CONCLUSION: Renal osteodystrophy changes were more pronounced in WT mice than in SOST-/- mice. The high bone mass phenotype of sclerostin deficiency was detectable also in the setting of chronic renal failure with severe secondary hyperparathyroidism.

Asunto(s)

Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Glicoproteínas/deficiencia , Proteínas Adaptadoras Transductoras de Señales , Animales , Femenino , Péptidos y Proteínas de Señalización Intercelular , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados

Asunto(s)

Calcifilaxia , Humanos

RESUMEN

Renal osteodystrophy is a feature of chronic kidney disease (CKD), with increasing prevalence as CKD progresses. This bone disease is responsible for major morbidity, including fractures, and a deterioration in the quality of life and its sequelae. Circulating biomarkers of renal osteodystrophy typically indicate bone turnover, but not other features of bone, like bone volume, mineralization, quality or strength. Bone turnover can be considered to be primarily a reflection of bone cell activity, in particular that of osteoblasts and osteoclasts. Since current treatments for bone disease usually target cellular activity, biomarkers are considered to be able to contribute to the decision-making for treatment and its follow-up. In CKD, one has to consider the impact of a diminished clearance of biomarkers or their altered metabolism, both potentially limiting its clinical use. Here, several aspects of the most frequently used biomarkers of bone turnover are reviewed, with an emphasis on the specific situation represented by CKD. This review is based on the overview lecture at the symposium held in Amsterdam, September 23, 2016: "The Bone In CKD", organized by the CKD-MBD working group of ERA-EDTA.

Asunto(s)

Remodelación Ósea , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Hormona Paratiroidea/sangre , Insuficiencia Renal Crónica/sangre , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/etiología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/fisiopatología , Colágeno Tipo I/sangre , Humanos , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , Insuficiencia Renal Crónica/complicaciones , Fosfatasa Ácida Tartratorresistente/sangre

RESUMEN

INTRODUCTION: Mounting evidence indicates that a disturbed Wnt-ß-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete. METHODS: We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage 4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls. We investigated associations with demographics, renal function, parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH)2 vitamin D, biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and bone turnover markers. RESULTS: Serum sclerostin, but not DKK1, increases in more advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH)2 vitamin D concentrations. Bone turnover markers are highest in hemodialysis patients presenting the combination of high PTH with low sclerostin level. Serum DKK1 levels are lower in CKD patients than in controls and are not associated with laboratory parameters of mineral metabolism. Interestingly, a direct association between DKK1 and platelet count was observed. CONCLUSION: In CKD, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients. DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet counts.

Asunto(s)

Proteínas Morfogenéticas Óseas/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Riñón/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Anciano , Plaquetas/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/fisiopatología , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Marcadores Genéticos , Voluntarios Sanos , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Diálisis Peritoneal , Fosfatos/metabolismo , Diálisis Renal , Vitamina D/sangre , Vía de Señalización Wnt/genética

Asunto(s)

Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/patología , Calcinosis/tratamiento farmacológico , Calcinosis/fisiopatología , Modelos Cardiovasculares , Vitamina K/administración & dosificación , Anciano , Válvula Aórtica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Estudios Prospectivos

RESUMEN

Background: Calcific uraemic arteriolopathy (CUA, calciphylaxis) is a rare disease predominantly in dialysis patients and associated with high mortality. Painful skin ulcerations and calcification of cutaneous arterioles characterize calciphylaxis. Methods: We established an observational, Internet-based registry allowing online notification for all German CUA cases. The registry recorded data about patient characteristics, biochemistry and therapies. Blood samples were stored in a central biobank. Results: Between 2006 and 2015, 253 CUA patients were recorded: median age 70 [interquartile range (IQR) 61-76] years, 60% females and 86% ( n = 207) dialysis patients, translating into an estimated annual incidence rate of 0.04% in German dialysis patients. Fifty-two per cent received vitamin K antagonists (VKAs) prior to CUA. Skin lesions were localized in 71% on the legs or gluteal region. In dialysis CUA patients median total serum calcium was 2.20 (IQR 2.06-2.37) mmol/L, phosphorus 1.67 (IQR 1.35-2.03) mmol/L, intact parathyroid hormone 147 (IQR 72-276) pg/mL and fetuin-A 0.21 (IQR 0.16-0.26) g/L (normal range 0.35-0.95). Median sclerostin, osteoprotegerin, TRAP5b, bone-specific alkaline phosphatase and c-terminal FGF23 levels were all elevated. The most frequently recorded therapeutic procedures in dialysis CUA patients were as follows: wound debridement (29% of cases), stopping VKA (25%), lowering calcium supply (24%), sodium thiosulphate (22%), application of vitamin K (18%), increase of dialysis duration/frequency (17%) and stoping active vitamin D (16%). Conclusions: Approximately 50% of CUA patients used VKA. Our data suggest that uncontrolled hyperparathyroidism is not the key determinant of calciphylaxis. Therapeutic strategies were heterogeneous. The experience of the German registry will help substantially to initiate a large-scale multinational CUA registry.

Asunto(s)

Calcifilaxia/diagnóstico , Fallo Renal Crónico/terapia , Sistema de Registros/estadística & datos numéricos , Diálisis Renal/efectos adversos , Vitamina K/antagonistas & inhibidores , Anciano , Calcifilaxia/tratamiento farmacológico , Calcifilaxia/etiología , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

Magnesium (Mg) is one of the most important cations in the body, playing an essential role in biological systems as co-factor for more than 300 essential enzymatic reactions. In the general population, low levels of Mg are associated with a high risk of cardio-vascular disease (CVD). Despite the accumulating literature data, the effect of Mg administration on mortality in chronic kidney disease (CKD) patients has never been investigated as a primary end-point. We conducted a systematic search of studies assessing the benefits and harms of Mg in CKD (stages 1 to 5 and 5D), and considered all randomized controlled trials (RCTs) and quasi-RCTs evaluating Mg-based interventions in CKD. As a phosphate binder, Mg salts offer a plausible opportunity for doubly favorable effects via reduction of intestinal phosphate absorption and addition of potentially beneficial effects via increasing circulating Mg levels. Mg supplementation might have a favorable effect on vascular calcification, although evidence for this is very slight. Although longitudinal data describe an association between low serum Mg levels and increased total and cardiovascular mortality, in patients with CKD, the existing RCTs reporting the effect of Mg supplementation on mortality failed to demonstrate any favorable effect. As with many other variables that influence hard end-points in nephrology, the role of Mg in CKD patients needs to be investigated in more depth. Additional research that is well-designed and directly targeting the role of Mg is needed as a consequence of limited existing evidence.

Asunto(s)

Riñón/efectos de los fármacos , Magnesio/farmacología , Magnesio/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Humanos , Riñón/metabolismo , Magnesio/administración & dosificación , Magnesio/efectos adversos , Insuficiencia Renal Crónica/metabolismo

RESUMEN

OBJECTIVES: The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to-renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients. METHODS: Cross-sectional data of the single-center "Eplerenone in Primary Hyperparathyroidism" trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included. RESULTS: Full data were available in 136 patients (mean age 67 ±â€Š10 years, 78% women). Median PTH was 99 (interquartile range: 82-124) pg/ml and mean calcium was 2.63 ±â€Š0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson's r = 0.241, P < 0.01) and DBP (r = 0.328, P < 0.01). In multivariate regression analyses, with adjustment for age, sex, PTH, FGF-23, traditional cardiovascular risk factors, antihypertensive medication and parameters of calcium metabolism ARR remained significantly and directly related with nocturnal BP (SBP: adjusted ß-coefficient = 0.289, P < 0.01; DBP: ß = 0.399, P < 0.01). The relationship between ARR and nocturnal SBP was exclusively present in patients with PTH levels above the median of 99 pg/ml. CONCLUSION: ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT.

Asunto(s)

Aldosterona/sangre , Presión Sanguínea , Factores de Crecimiento de Fibroblastos/sangre , Hiperparatiroidismo Primario/sangre , Hormona Paratiroidea/sangre , Renina/sangre , Anciano , Antihipertensivos/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial , Calcio/sangre , Ritmo Circadiano , Estudios Transversales , Diástole , Eplerenona , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/fisiopatología , Hipertensión/sangre , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores Sexuales , Espironolactona/análogos & derivados , Espironolactona/uso terapéutico , Sístole

RESUMEN

BACKGROUND: Sclerostin is an endocrine regulator in chronic kidney disease - mineral and bone disorder (CKD-MBD). Validation of assay comparability and pre-analytical handling is mandatory for establishment of sclerostin as a biomarker. METHODS: Blood samples (serum, EDTA, heparin and citrate plasma) were obtained from 12 hemodialysis (HD) patients after the long dialysis interval. Passing-Bablok regression analysis and Bland-Altman difference plots were used to evaluate the agreement between sclerostin levels measured with two commercially available ELISAs from TECOmedical and Biomedica. RESULTS: Independent of the sample type, the agreement of the two assays was poor with a strong proportional but no systematic bias. Compared to the TECOmedical assay, the Biomedica test yielded almost 2-fold higher sclerostin values throughout all sample types. Spike recovery and linear dilution studies revealed a higher accuracy of the TECOmedical assay (97% and 96%) compared to the Biomedica assay (118% and 78%). Sclerostin levels were stable within 4 hours after sample collection, in particular when analyzed in plasma. In contrast to the Biomedica assay, the TECOmedical showed a systematic but no proportional bias between serum and plasma samples with higher values for plasma samples. Among the 3 different plasma samples no systematic error could be documented. CONCLUSION: Careful consideration of the pre-analytical handling and comparative assay validation are necessary to facilitate a more differentiated interpretation of studies reporting circulating sclerostin levels. The presence of a proportional bias demonstrates that in HD patients the two ELISAs for measuring sclerostin should not be used interchangeably. Furthermore, caution is necessary when comparing sclerostin results obtained from different blood sample types.

RESUMEN

Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare disease predominantly occurring in comorbidity with dialysis. Due to the very low frequency of CUA, prospective studies on its management are lacking and even anecdotal reports on treatment remain scarce. Therefore, calciphylaxis is still a challenging disease with dismal prognosis urgently requiring adequate strategies for diagnosis and treatment.In an attempt to fill some of the current gaps in evidence on various, highly debated and controversial aspects of dialysis-associated calciphylaxis, 13 international experts joined the 1st Consensus Conference on CUA, held in Leuven, Belgium on 21 September 2015. The conference was supported by the European Calciphylaxis Network (EuCalNet), which is a task force of the ERA-EDTA scientific working group on Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD). After an intense discussion, a 9-point Likert scale questionnaire regarding 20 items on calciphylaxis was anonymously answered by each participant. These 20 items addressed unsolved issues in terms of diagnosis and management of calciphylaxis. On the one hand, the analysis of the expert opinions identified areas of general consensus, which might be a valuable aid for physicians treating such a disease with less experience in the field. On the other hand, some topics such as the pertinence of skin biopsy and administration of certain treatments revealed divergent opinions. The aim of the present summary report is to provide some guidance for clinicians who face patients with calciphylaxis in the current setting of absence of evidence-based medicine.

Asunto(s)

Calcifilaxia/patología , Calcifilaxia/prevención & control , Evaluación de Necesidades , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Humanos