RESUMEN
Anemia is a frequent complication of kidney disease. When severe, it causes symptoms that can be debilitating. The course of anemia tends to track the decline in kidney function, with prevalence increasing in more advanced disease. Although the most common cause is relative erythropoietin deficiency, other factors such as reduced iron availability contribute to the pathobiology. In this review, we use cases to explore the surprising complexity of decision-making in management of renal anemia.
Asunto(s)
Anemia/terapia , Enfermedades Renales/terapia , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Eritropoyetina/sangre , Eritropoyetina/deficiencia , Humanos , Hierro/sangre , Deficiencias de Hierro , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Pautas de la Práctica en Medicina/normas , PrevalenciaRESUMEN
BACKGROUND: The use of older data and references is becoming increasingly disfavored for publication. A myopic focus on newer research risks losing sight of important research questions already addressed by now-invisible older studies. This creates a 'Groundhog Day' effect as illustrated by the 1993 movie of this name in which the protagonist has to relive the same day (Groundhog Day) over and over and over within a world with no memory of it. This article examines the consequences of the recent preference for newer data and references in current publication practices and is intended to stimulate new consideration of the utility of selected older data and references for the advancement of scientific knowledge. METHODS: Examples from the literature are used to exemplify the value of older data and older references. To illustrate the recency of references published in original medical research articles in a selected sample of recent academic medical journals, original research articles were examined in recent issues in selected psychiatry, medicine, and surgery journals. RESULTS: The literature examined reflected this article's initial assertion that journals are emphasizing the publication of research with newer data and more recent references. CONCLUSIONS: The current valuation of newer data above older data fails to appreciate the fact that new data eventually become old, and that old data were once new. The bias demonstrated in arbitrary policies pertaining to older data and older references can be addressed by instituting comparable treatment of older and newer data and references.
Asunto(s)
Psiquiatría , HumanosRESUMEN
BACKGROUND: Elevated serum phosphorus concentrations are common among maintenance hemodialysis patients. Protein is a major source of dietary phosphate, but restriction of protein intake can result in hypoalbuminemia and protein-energy wasting. We hypothesized that sucroferric oxyhydroxide (SO), a potent phosphate binder with a low pill burden, may reduce serum phosphorus levels in hemodialysis patients with hypoalbuminemia without adversely impacting albumin levels or dietary intake of protein. METHODS: We retrospectively examined de-identified data from 79 adult, in-center hemodialysis patients with baseline hypoalbuminemia (≤ 3.5 g/dL) switched to SO as part of routine clinical care for at least 1 year. Temporal changes (3-month intervals from baseline through Q4) in phosphate binder pill burden, serum phosphorous levels, nutritional markers, and equilibrated Kt/V were analyzed. Data from a matched reference group of non-hypoalbuminemic patients (N = 79) switched to SO were also examined. RESULTS: SO therapy was associated with a mean reduction of 45.7 and 45.1% in daily phosphate binder pill burden, and a mean reduction of 0.4 mg/dL and 0.51 mg/dL in serum phosphorus levels for the hypoalbuminemic and non-hypoalbuminemic patients, respectively. Hypoalbuminemic patients demonstrated significant increases in mean serum albumin levels from 3.50 mg/dL at baseline to 3.69, 3.74, 3.70, and 3.69 mg/dL during Q1 through Q4, respectively (P < 0.0001), whereas serum albumin levels remained unchanged in the non-hypoalbuminemic group. CONCLUSIONS: Both hypoalbuminemic and non-hypoalbuminemic patients switching to SO exhibited significant reductions in serum phosphorus concentrations and daily phosphate binder pill burden. Among hypoalbuminemic patients, the initiation of SO therapy was also associated with increases in serum albumin, suggesting therapy may have allowed patients to increase their dietary intake of protein.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Compuestos Férricos/administración & dosificación , Hipoalbuminemia/sangre , Fósforo/sangre , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Sacarosa/administración & dosificación , Estudios de Cohortes , Creatinina/sangre , Combinación de Medicamentos , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fosfatos/metabolismo , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Albúmina Sérica/metabolismoRESUMEN
BACKGROUND: A database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care. METHODS: Adult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL. RESULTS: At baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001). CONCLUSION: Among PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed.
Asunto(s)
Compuestos Férricos/administración & dosificación , Hiperfosfatemia/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Sacarosa/administración & dosificación , Adulto , Anciano , Combinación de Medicamentos , Femenino , Humanos , Hiperfosfatemia/etiología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Peritoneal , Fósforo/sangre , Estudios RetrospectivosRESUMEN
The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.
Asunto(s)
Calcimiméticos/farmacología , Cinacalcet/farmacología , Ergocalciferoles/farmacología , Hiperparatiroidismo Secundario/terapia , Células Oxífilas/efectos de los fármacos , Glándulas Paratiroides/efectos de los fármacos , Insuficiencia Renal Crónica/tratamiento farmacológico , Adulto , Calcimiméticos/uso terapéutico , Calcitriol/análogos & derivados , Transdiferenciación Celular/efectos de los fármacos , Cinacalcet/uso terapéutico , Quimioterapia Combinada/métodos , Ergocalciferoles/uso terapéutico , Femenino , Humanos , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/orina , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/citología , Glándulas Paratiroides/metabolismo , Glándulas Paratiroides/cirugía , Paratiroidectomía , Receptores Sensibles al Calcio/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/orina , Uremia/complicaciones , Uremia/tratamiento farmacológico , Uremia/orina , Vitamina D/análogos & derivadosRESUMEN
AIMS: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients. MATERIALS AND METHODS: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 - 3) and 6 months (SO 4 - 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed. RESULTS: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 - 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 - 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%). CONCLUSIONS: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day.â©.
Asunto(s)
Compuestos Férricos/uso terapéutico , Hiperfosfatemia/tratamiento farmacológico , Diálisis Renal , Sacarosa/uso terapéutico , Adulto , Anciano , Combinación de Medicamentos , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Fósforo/sangre , Diálisis Renal/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Use of existing therapies for secondary hyperparathyroidism (SHPT), such as calcitriol or paricalcitol, is frequently limited by the development of hypercalcemia. 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD; DP001) is a novel and a more potent vitamin D receptor activator (VDRA) that more selectively localizes in the parathyroid gland, and has a wider therapeutic margin in the uremic rat model than calcitriol and paricalcitol. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Hemodialysis patients were enrolled and dosed with 110, 220, 330, 440, or 550 ng of 2MD orally thrice weekly for 4 weeks. Responders were defined as patients having a ≥30% reduction in parathyroid hormone (PTH) from baseline, and were assessed at weeks 2 and 4. RESULTS: Of 31 patients recruited, 24 completed the 4-week treatment. There was little or no reduction in PTH in the 110 and 220 ng dose cohorts. Higher dose cohorts had greater PTH suppression with more than half the patients in the 440 and 550 ng dose cohorts considered responders (≥30% PTH reduction from baseline). None had oversuppression of PTH or hypercalcemia (corrected serum calcium >10.6 mg/dl). Plasma drug concentration increased with increasing dose, and all responders achieved a 2MD concentration of ≥1.5 pg/ml. All dose levels of 2MD were well tolerated without safety concerns. CONCLUSIONS: In hemodialysis patients with SHPT, 2MD, at thrice weekly oral doses of 440 and 550 ng, is well tolerated and effectively suppresses PTH without hypercalcemia. Future studies are needed to study the long-term implications of treating ESRD patients with this novel VDRA.
Asunto(s)
Calcitriol/análogos & derivados , Hiperparatiroidismo Secundario/tratamiento farmacológico , Anciano , Calcitriol/uso terapéutico , Femenino , Humanos , Hiperparatiroidismo Secundario/etiología , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Iron deficiency anaemia is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and is often treated with oral or intravenous (IV) iron therapy. This trial compared the efficacy and safety of IV iron isomaltoside 1000 (Monofer®) and oral iron in NDD-CKD patients with renal-related anaemia. METHODS: The trial was a Phase III open-label, comparative, multicentre, non-inferiority trial conducted in 351 iron-deficient NDD-CKD patients, randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 8 weeks (Group B). The patients in Group A were randomized into A1 (infusion of max. 1000 mg single doses over 15 min) and A2 (bolus injections of 500 mg over 2 min). A modified Ganzoni formula was used to calculate IV iron need. The primary end point was change in haemoglobin concentrations from baseline to Week 4. RESULTS: Iron isomaltoside 1000 was both non-inferior to oral iron at Week 4 (P < 0.001) and sustained a superior increase in haemoglobin from Week 3 until the end of the study at Week 8 (P = 0.009 at Week 3). The haemoglobin response was more pronounced with iron isomaltoside 1000 doses ≥1000 mg (P < 0.05). Serum-ferritin and transferrin saturation concentrations were also significantly increased with IV iron. Adverse drug reactions were observed in 10.5% in the iron isomaltoside 1000 group and 10.3% in the oral iron group. More patients treated with oral iron sulphate withdrew from the study due to adverse events (4.3 versus 0.9%, P = 0.2). CONCLUSIONS: Iron isomaltoside 1000 was more efficacious than oral iron for increase in haemoglobin and proved to be well tolerated at the tested dose levels in NDD-CKD patients.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Disacáridos/uso terapéutico , Compuestos Férricos/uso terapéutico , Hierro/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/etiología , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.
Asunto(s)
Anemia Ferropénica/prevención & control , Eritropoyetina/uso terapéutico , Hematínicos/uso terapéutico , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Anemia Ferropénica/etiología , Animales , Estudios Transversales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eritropoyetina/efectos adversos , Ferritinas/metabolismo , Hematínicos/efectos adversos , Humanos , Infusiones Intravenosas , Compuestos de Hierro/uso terapéutico , Fallo Renal Crónico/complicaciones , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/métodos , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients. METHODS: This was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sucrose (Group B). Subjects in Group A were equally divided into A1 (500 mg single bolus injection) and A2 (500 mg split dose). Group B were also treated with 500 mg split dose. The primary end point was the proportion of subjects with haemoglobin (Hb) in the target range 9.5-12.5 g/dL at 6 weeks. Secondary outcome measures included haematology parameters and safety parameters. RESULTS: A total of 351 subjects were enrolled. Both treatments showed similar efficacy with >82% of subjects with Hb in the target range (non-inferiority, P = 0.01). Similar results were found when comparing subgroups A1 and A2 with Group B. No statistical significant change in Hb concentration was found between any of the groups. There was a significant increase in ferritin from baseline to Weeks 1, 2 and 4 in Group A compared with Group B (Weeks 1 and 2: P < 0.001; Week 4: P = 0.002). There was a significant higher increase in reticulocyte count in Group A compared with Group B at Week 1 (P < 0.001). The frequency, type and severity of adverse events were similar. CONCLUSIONS: Iron isomaltoside 1000 and iron sucrose have comparative efficacy in maintaining Hb concentrations in haemodialysis subjects and both preparations were well tolerated with a similar short-term safety profile.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Disacáridos/uso terapéutico , Compuestos Férricos/uso terapéutico , Ácido Glucárico/uso terapéutico , Hematínicos/uso terapéutico , Diálisis Renal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/etiología , Intervención Educativa Precoz , Femenino , Sacarato de Óxido Férrico , Ferritinas/metabolismo , Hemoglobinas/análisis , Humanos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/terapia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Iron deficiency is a major factor in the prevalence and severity of anemia in patients with chronic kidney disease (CKD). We review the pathophysiology impairing normal intestinal iron absorption in CKD and compare the characteristics of newer intravenous (i.v.) iron agents to the longstanding i.v. iron products in the market. RECENT FINDINGS: The newer iron products, ferumoxytol, ferric carboxymaltose, and iron isomaltoside, more avidly bind iron, minimizing the release of labile iron during infusions, thus permitting large dose infusions. These irons also have more complex carbohydrate shells than their predecessors, which may also diminish reactions. Newer agents can be routinely administered at higher single doses, in as little as 15âmin, with an acceptable safety profile. SUMMARY: Newer i.v. iron products permit the rapid, and sometimes complete, repletion of iron-deficient patients with a single dose. However, further studies examining the long-term risks and benefits of i.v. iron repletion are needed.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Hematínicos/administración & dosificación , Insuficiencia Renal Crónica/cirugía , Administración Intravenosa , Anemia Ferropénica/sangre , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Disacáridos/administración & dosificación , Compuestos Férricos/administración & dosificación , Óxido Ferrosoférrico/administración & dosificación , Hematínicos/efectos adversos , Hematínicos/farmacocinética , Homeostasis , Humanos , Absorción Intestinal , Maltosa/administración & dosificación , Maltosa/análogos & derivados , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is associated with elevations in serum phosphate, calcium-phosphorus product and bone-specific alkaline phosphatase (BAP), with attendant risks of cardiovascular and bone disorders. Active vitamin D can suppress parathyroid hormone (PTH), but may raise serum calcium and phosphate concentrations. Paricalcitol, a selective vitamin D activator, suppressed PTH in CKD patients (stages 3 and 4) with secondary hyperparathyroidism (SHPT) with minimal changes in calcium and phosphate metabolism. METHODS: The VITAL study enrolled patients with CKD stages 2-4. We examined the effect and relationship of paricalcitol to calcium and phosphate metabolism and bone markers in a post hoc analysis of VITAL. The study comprised patients with diabetic nephropathy enrolled in a double-blind, placebo-controlled, randomized trial of paricalcitol (1 or 2 µg/day). Urinary and serum calcium and phosphate, serum BAP, and intact PTH (iPTH) concentrations were measured throughout the study. RESULTS: Baseline demographics and calcium, phosphate, PTH (49% with iPTH <70 pg/mL), and BAP concentrations were similar between groups. A transient, modest yet significant increase in phosphate was observed for paricalcitol 2 µg/day (+0.29 mg/dL; P < 0.001). Dose-dependent increases in serum and urinary calcium were observed; however, there were few cases of hypercalcemia: one in the 1-µg/day group (1.1%) and three in the 2-µg/day group (3.2%). Significant reductions in BAP were observed that persisted for 60 days after paricalcitol discontinuation (P < 0.001 for combined paricalcitol groups versus placebo). Paricalcitol dose-dependent reductions in iPTH were observed. Paricalcitol in CKD patients (±SHPT) was associated with modest increases in calcium and phosphate. CONCLUSION: Paricalcitol reduces BAP levels, which may be beneficial for reducing vascular calcification. TRIAL REGISTRATION: Trial is registered with ClinicalTrials.gov, number NCT00421733.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Biomarcadores/metabolismo , Huesos/metabolismo , Calcio/metabolismo , Nefropatías Diabéticas/metabolismo , Ergocalciferoles/farmacología , Fosfatos/metabolismo , Anciano , Conservadores de la Densidad Ósea/farmacología , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/análogos & derivadosRESUMEN
The Normal Hematocrit Trial (NHT) was the largest trial of epoetin randomizing 1265 hemodialysis patients with cardiac disease to lower (9-11 g/dl) or higher (13-15 g/dl) hemoglobin (Hgb), hypothesizing that higher Hgb would reduce mortality, and improve survival and quality of life. The trial was terminated early, and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points (death or myocardial infarct), or risk ratio 1.3, 95% confidence interval (CI), 0.9-1.90, but the P-value was not given, and all-cause death risk was not reported. A higher target reportedly did not increase hospitalization rates, but did significantly improve the 'physical function' domain of quality of life. Comparing the 1996 Food and Drug Administration (FDA)-filed clinical trial report to the 1998 publication, however, found several discrepancies. Among these, the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile, and despite being a secondary end point, reported only the association of achieved Hgb with higher quality of life score. Randomization to the higher target had actually increased the risk for the primary end point (risk ratio 1.28, 95% CI=1.06-1.56; P=0.0112; 99.92% CI=0.92-1.78), the risk of death (risk ratio 1.27, 95% CI=1.04-1.54), non-access thrombotic events (P=0.041), and hospitalization rate (P=0.04), while 'physical function' did not improve (P=0.88). Hence, disclosure of these results in the 1998 publication or access to the FDA-filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/efectos adversos , Cardiopatías/terapia , Hematínicos/efectos adversos , Hematócrito , Hemoglobinas/metabolismo , Enfermedades Renales/terapia , Calidad de Vida , Diálisis Renal , Acceso a la Información , Anemia/sangre , Anemia/diagnóstico , Anemia/mortalidad , Anemia/psicología , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Terminación Anticipada de los Ensayos Clínicos , Emociones , Medicina Basada en la Evidencia , Estado de Salud , Cardiopatías/sangre , Cardiopatías/mortalidad , Cardiopatías/psicología , Hospitalización , Humanos , Estimación de Kaplan-Meier , Enfermedades Renales/sangre , Enfermedades Renales/mortalidad , Enfermedades Renales/psicología , Salud Mental , Seguridad del Paciente , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Medición de Riesgo , Factores de Riesgo , Conducta Social , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Most of the major vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D circulates in a tightly bound state to vitamin D-binding protein (DBP), rendering this fraction unavailable for biological action. A smaller fraction, loosely bound to albumin or circulating freely, is bioavailable, and hence bioactive. This Commentary discusses the free hormone hypothesis and the role of DBP in vitamin D metabolism.
Asunto(s)
Remodelación Ósea , Huesos/metabolismo , Fallo Renal Crónico/terapia , Diálisis Renal , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Femenino , Humanos , Masculino , Vitamina D/sangreRESUMEN
Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in > 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice.
Asunto(s)
Hiperfosfatemia , Combinación de Medicamentos , Compuestos Férricos/uso terapéutico , Humanos , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/etiología , Hierro/uso terapéutico , Fosfatos , Fósforo , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Sacarosa/uso terapéuticoRESUMEN
Purpose: In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018-2019) cohort. Patients and Methods: Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1-Q4) and analyzed using linear mixed-effects regression and Cochran's Q test. These results were contrasted with findings from a historical (2014-2015) cohort (N = 530). Results: The proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively; P < 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (P < 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort. Conclusion: Despite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.
RESUMEN
BACKGROUND AND OBJECTIVES: Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis with a baseline hemoglobin of 8-11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28-52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability. RESULTS: Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%). CONCLUSIONS: Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033.