RESUMEN
Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Asunto(s)
Lesión Pulmonar Aguda , FN-kappa B , Humanos , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Pulmón , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/farmacología , Proteínas de Unión a Fosfato/uso terapéutico , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Citotóxicas Formadoras de Poros/farmacología , Proteínas Citotóxicas Formadoras de Poros/uso terapéuticoRESUMEN
Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Asunto(s)
Humanos , FN-kappa B/metabolismo , Lipopolisacáridos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lesión Pulmonar Aguda/metabolismo , Pulmón , Proteínas de Unión a Fosfato/uso terapéutico , Proteínas Citotóxicas Formadoras de Poros/uso terapéuticoRESUMEN
Sepsis, a life-threating illness caused by deregulated host immune responses to infections, is characterized by overproduction of multiple reactive oxygen and nitrogen species (RONS) and excessive pyroptosis, leading to high mortality. However, there is still no approved specific molecular therapy to treat sepsis. Here we reported drug-free tea polyphenols nanoparticles (TPNs) with intrinsic broad-spectrum RONS scavenging and pyroptosis-blocking activities to treat endotoxin (LPS)-induced sepsis in mice. The RONS scavenging activities originated from the polyphenols-derived structure, while the pyroptosis blockage was achieved by inhibiting gasdermin D (GSDMD) mediating the pore formation and membrane rupture, showing multifunctionalities for sepsis therapy. Notably, TPNs suppress GSDMD by inhibiting the oligomerization of GSDMD rather than the cleavage of GSDMD, thus displaying high pyroptosis-inhibition efficiency. As a result, TPNs showed an excellent therapeutic efficacy in sepsis mice model, as evidenced by survival rate improvement, hypothermia amelioration, and the organ damage protection. Collectively, TPNs present biocompatible candidates for the treatment of sepsis.
Asunto(s)
Nanopartículas , Sepsis , Animales , Endotoxinas , Péptidos y Proteínas de Señalización Intracelular/uso terapéutico , Ratones , Proteínas de Unión a Fosfato/uso terapéutico , Polifenoles/farmacología , Polifenoles/uso terapéutico , Piroptosis , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico , TéAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Sulfonamidas/efectos adversos , Síndrome de Lisis Tumoral/etiología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Citarabina/uso terapéutico , Decitabina/administración & dosificación , Femenino , Fluidoterapia , Humanos , Hidroxiurea/uso terapéutico , Incidencia , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Aguda/complicaciones , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/genética , Leucocitosis/tratamiento farmacológico , Leucocitosis/etiología , Masculino , Persona de Mediana Edad , Proteínas de Unión a Fosfato/uso terapéutico , Fósforo/sangre , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Estudios Retrospectivos , Sulfonamidas/administración & dosificación , Urato Oxidasa/uso terapéutico , Ácido Úrico/sangreRESUMEN
Elevated serum phosphorus levels are common in patients with chronic kidney disease and are associated with heart and vascular disease, conditions that in turn are associated with increased mortality. Accurately managing phosphorus intake by restricting dietary protein alone can prove challenging because protein from different sources can contain varying amounts of available phosphorus. Additives used in processed foods frequently are high in inorganic phosphorus, which is readily absorbed, compounding this difficulty. Recent evidence suggests that dietary protein restriction in some cases may do more harm than good in some patients treated with maintenance hemodialysis because protein restriction can lead to protein-energy wasting, which is associated with increased mortality. Accordingly, phosphorus binders are important for managing hyperphosphatemia in dialysis patients. Managing hyperphosphatemia in patients with late-stage chronic kidney disease requires an individualized approach, involving a combination of adequate dietary advice, phosphate-binder use, and adjustments to dialysis prescription. We speculate that increased use of phosphate binders could allow patients to eat more protein-rich foods and that communicating this to patients might increase their perception of their need for phosphate binders, providing an incentive to improve adherence. The aim of this review is to discuss the challenges involved in maintaining adequate nutrition while controlling phosphorus levels in patients on maintenance hemodialysis therapy.
Asunto(s)
Terapia Nutricional , Fósforo/sangre , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Dieta con Restricción de Proteínas , Proteínas en la Dieta/efectos adversos , Manejo de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Unión a Fosfato/uso terapéutico , Resultado del TratamientoRESUMEN
The mineral and bone disorder of chronic kidney disease remains a challenging complication in pediatric end-stage renal disease. Here, we assessed symptoms, risk factors and management of this disorder in 890 children and adolescents from 24 countries reported to the International Pediatric Peritoneal Dialysis Network Registry. Signs of this disease were most common in North American patients. The prevalence of hyperphosphatemia increased with age from 6% in young infants to 81% in adolescents. Serum parathyroid hormone (PTH) was outside the guideline targets in the majority of patients and associated with low calcium, high phosphorus, acidosis, dialysis vintage and female gender. Serum calcium was associated with dialytic calcium exposure, serum phosphorus with low residual renal function and pubertal status. PTH levels were highest in Latin America and lowest in Europe. Vitamin D and its active analogs were most frequently administered in Europe; calcium-free phosphate binders and cinacalcet in North America. Clinical and radiological symptoms markedly increased when PTH exceeded 300 pg/ml, the risk of hypercalcemia increased with levels below 100 pg/ml, and time-averaged PTH concentrations above 500 pg/ml were associated with impaired longitudinal growth. Hence, the symptoms and management of the mineral and bone disorder of chronic kidney disease in children on peritoneal dialysis showed substantial regional variation. Our findings support a PTH target range of 100-300 pg/ml in the pediatric age group.
Asunto(s)
Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/etiología , Hipocalcemia/tratamiento farmacológico , Hipocalcemia/etiología , Fallo Renal Crónico/complicaciones , Diálisis Peritoneal , Adolescente , Calcio/sangre , Niño , Preescolar , Cinacalcet , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hiperfosfatemia/epidemiología , Hipocalcemia/epidemiología , Lactante , Fallo Renal Crónico/sangre , América Latina/epidemiología , Masculino , Naftalenos/uso terapéutico , América del Norte/epidemiología , Hormona Paratiroidea/sangre , Proteínas de Unión a Fosfato/uso terapéutico , Fósforo/sangre , Estudios Prospectivos , Sistema de Registros , Vitamina D/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease (ESRD) in patients undergoing periodic hemodialysis. The relationship between hyperphosphatemia and cardiovascular calcification, with the consequences of high morbidity and mortality after cardiovascular events, is well-defined. Hyperphosphatemia is treated by dietary limitation of phosphorus ingestion and by phosphate binders, but only half of ESRD patients fall within the range of K/DOQI guidelines. OBJECTIVE AND METHODS: We summarize the results of our studies on salivary phosphate secretion in hemodialysis (HD) and chronic kidney disease (CKD) patients, and on the habit of HD patients to drink beverages with a high or low phosphate content. We also examine the correlation between hyperphosphoremia and the phosphate content of common beverages consumed by HD patients. RESULTS AND CONCLUSIONS: Higher levels of salivary phosphate secretion were found in HD and in CKD patients, along with a relationship between serum phosphorus levels and a high phosphate content of beverages in HD patients.
Asunto(s)
Bebidas/análisis , Hiperfosfatemia/terapia , Fallo Renal Crónico/terapia , Fosfatos/análisis , Fósforo , Saliva/química , Femenino , Humanos , Hiperfosfatemia/etiología , Hiperfosfatemia/metabolismo , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Unión a Fosfato/uso terapéutico , Fósforo/administración & dosificación , Fósforo/efectos adversos , Fósforo/análisis , Diálisis RenalRESUMEN
Elevated serum phosphorus has been identified as a cardiovascular risk factor in chronic kidney disease (CKD) patients and a clear understanding of phosphorus homeostasis is very important for practicing nephrologists. At any particular point, serum phosphorus levels reflect the balance between movements of this mineral from and into the intestine, bone, intracellular space, and kidneys. We briefly review here all these exchanges with a particular emphasis on dietary phosphorus intake. Despite all the oral phosphorus binders currently available in the market, dietary restriction of this mineral remains a cornerstone for the prevention and treatment of hyperphosphatemia. An effective restriction of dietary intake of phosphorus requires prescription of a moderate protein intake (0.9-1.0 g/kg/day) and restricted consumption of highly processed fast and convenience foods. Phosphorus added during food processing is an important source of this mineral because of its magnitude and high bioavailabilty. Moreover, as food manufacturers are not required to label the amount of phosphorus added during food processing, a significant amount of the current daily phosphorus intake remains unaccounted when estimating phosphorus intake in CKD patients. The recent development of low phosphorus-containing food products represents a very useful addition for CKD patients.
Asunto(s)
Homeostasis/fisiología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/fisiopatología , Trastornos del Metabolismo del Fósforo/prevención & control , Trastornos del Metabolismo del Fósforo/fisiopatología , Fósforo Dietético/administración & dosificación , Fósforo Dietético/sangre , Disponibilidad Biológica , Calcio de la Dieta/administración & dosificación , Quelantes/uso terapéutico , Análisis de los Alimentos , Etiquetado de Alimentos , Humanos , Absorción Intestinal/fisiología , Proteínas de Unión a Fosfato/uso terapéutico , Diálisis RenalRESUMEN
Hyperphosphataemia is a major problem in patients with chronic kidney disease as it has been associated with increased morbidity and mortality. Over the last four decades, different modalities have been applied to treat hyperphosphataemia with varying degrees of success. Unfortunately, treatment strategies have led to unforeseen complications. These have prompted the development of new classes of medications with potentially better efficacy and few short-term and long-term side effects. This article reviews the causes, mechanism and management of hyperphosphataemia.
Asunto(s)
Fallo Renal Crónico/sangre , Fósforo/sangre , Diálisis Renal , Adulto , Cinacalcet , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/terapia , Naftalenos/uso terapéutico , Proteínas de Unión a Fosfato/uso terapéutico , Poliaminas/uso terapéutico , SevelamerRESUMEN
Derangements of mineral metabolism occur during the early stages of chronic kidney disease (CKD). Hyperphosphatemia develops in the majority of patients with ESRD and has long been associated with progression of secondary hyperparathyroidism and renal osteodystrophy. More recent observational data have associated hyperphosphatemia with increased cardiovascular mortality among dialysis patients. Adequate control of serum phosphorus remains a cornerstone in the clinical management of patients with CKD not only to attenuate the progression of secondary hyperparathyroidism but also possibly to reduce the risk for vascular calcification and cardiovascular mortality. These measures include dietary phosphorus restriction, dialysis, and oral phosphate binders. Dietary restriction is limited in advanced stages of CKD. Phosphate binders are necessary to limit dietary absorption of phosphorus. Aluminum hydroxide is an efficient binder; however, its use has been nearly eliminated because of concerns of toxicity. Calcium salts are inexpensive and have been used effectively worldwide as an alternative to aluminum. Concerns of calcium overload have led to the investigation of alternatives. Currently, only two Food and Drug Administration-approved noncalcium, nonaluminum binders are available. Sevelamer hydrochloride is an exchange resin and was not as effective as calcium acetate in meeting new guideline recommendations in one double-blind clinical trial. Lanthanum carbonate is a rare earth element and has been studied less extensively. Concerns of long-term administration and toxicity exist. Furthermore, these agents are significantly more expensive than calcium salts, which may contribute to patient noncompliance.
Asunto(s)
Fallo Renal Crónico/terapia , Proteínas de Unión a Fosfato/uso terapéutico , Fosfatos/sangre , Humanos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Fósforo/administración & dosificación , Diálisis RenalRESUMEN
Secondary hyperparathyroidism (SHP) is still an early and frequent complication of chronic renal disease (CRD). Currently, CRD is an independent cardiovascular risk factor, and calcium-phosphorus metabolism is one of the modifiable related factors. In this first article, we summarize the recent SHP treatment paradigm shift in dialysis patients, derived from the better knowledge and understanding of vascular calcification. We analyze the most recent guidelines (K/DOQI), and describe the general implications of hyperphosphatemia, as well as our therapeutic approach with phosphorus-binders. Since sevelamer additionally presents some pleiotropic effects and it attenuates the progression of vascular calcification, we consider it in the first-line of treatment despite it is not yet demonstrated a survival benefit. We also minimize the use of elemental calcium to a maximum of 1000 to 1500 mg/day. Lanthanum carbonate may well be an important therapeutic agent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play a role. All these drugs, isolated or in combination, are important in the treatment of SHP since a great deal of its success and the avoidance of some dialysis-related complications depend on an efficient phosphorus control.
Asunto(s)
Hiperparatiroidismo Secundario/terapia , Fallo Renal Crónico/terapia , Diálisis Renal , Algoritmos , Ácidos y Sales Biliares/administración & dosificación , Ácidos y Sales Biliares/uso terapéutico , Calcio/administración & dosificación , Calcio/metabolismo , Calcio/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Progresión de la Enfermedad , Quimioterapia Combinada , Compuestos Epoxi/administración & dosificación , Compuestos Epoxi/uso terapéutico , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/uso terapéutico , Humanos , Hiperparatiroidismo Secundario/etiología , Fallo Renal Crónico/complicaciones , Lantano/administración & dosificación , Lantano/uso terapéutico , Masculino , Análisis Multivariante , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Proteínas de Unión a Fosfato/uso terapéutico , Fosfatos/sangre , Fosfatos/metabolismo , Fósforo/metabolismo , Poliaminas , Polietilenos/administración & dosificación , Polietilenos/uso terapéutico , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/efectos adversos , Factores de Riesgo , Sevelamer , Factores de TiempoRESUMEN
UNLABELLED: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.
Asunto(s)
Calcio/química , Compuestos Epoxi/farmacología , Fallo Renal Crónico/sangre , Vértebras Lumbares/patología , Proteínas de Unión a Fosfato/uso terapéutico , Fosfatos/química , Polietilenos/farmacología , Anciano , Fosfatasa Alcalina/metabolismo , Aorta/patología , Biomarcadores/sangre , Huesos/metabolismo , Calcio/metabolismo , Electrones , Femenino , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Vértebras Lumbares/metabolismo , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/metabolismo , Proteínas de Unión a Fosfato/química , Fósforo , Poliaminas , Polímeros/química , Diálisis Renal/efectos adversos , Suero/metabolismo , Sevelamer , Columna Vertebral/patología , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Reports on acid-base side effects of sevelamer hydrochloride (SH), a new aluminum (Al)- and calcium (Ca)-free phosphate binder are rare and conflicting. In a retrospective analysis, we evaluated SH impact on metabolic acidosis and serum potassium (K) in hemodialysis (HD) patients. Two groups of stable HD patients were studied. Group A included 17 patients, M/F=15/2, 64 (42-80) years old, dialyzed since 130 (34-253) months, under SH for 24 months. Group B serving as controls was made of 7 patients, M/F=4/3, 67 (48-91) years old, dialyzed since 67 (27-174) months, under CaCO3 and/or Al(OH)3 as phosphate binders also for 24 months. Bicarbonate (BIC), K, Ca, phosphorus (P), Ca x P, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were recorded before (MO) and at the end (M24) of 24-month SH or CaCO3-Al(OH)3 treatment in group A and B patients. In group A, BIC fell from 20.02 +/- 1.43 to 17.89 +/- 2.30 mEq/ L, P=.002; and K rose from 5.45 +/- 0.51 to 5.75 +/- 0.49 mEq/L, P=0.02. In group B, BIC (19.8 +/- 3.03 to 19.0 +/- 3.3 mEq/L) and K (5.01 +/- 0.8 to 4.9 +/- 1.1 mEq/L) had nonsignificant changes. In group A, iPTH rose from 132.82 +/- 124.08 to 326.89 +/- 283.91 pg/mL, P=.0008; P fell from 5.92 +/- 1.48 to 4.9 +/- 1.01, P=.02; and Ca x P decreased from 52.04 +/- 9.7 to 45.58 +/- 10.42 mg2/dL2, P=.04. In group B, changes in iPTH from 240.71 +/- 174.7 to 318.57 +/- 260.2 pg/mL, P from 4.9 +/- 0.5 to 4.8 +/- 1.3 mg/dL, and CaxP product from 44.3 +/- 6.6 to 44 +/- 11.2 mg2/dL2 were nonsignificant. The changes observed in Ca and ALP in both groups were nonsignificant. Correlations in group A between metabolic acidosis (BIC) and SH doses, or iPTH and BIC, Ca, or P changes, were also found to be nonsignificant. Long-term use of SH, effectively controlling serum P levels and Ca x P values, is associated with acidosis aggravation and hyperkaliemia. Worsening of secondary hyperparathyroidism, also noted, needs to be confirmed and could be related to Ca/Al salt discontinuation and to metabolic acidosis aggravation itself.
Asunto(s)
Acidosis/inducido químicamente , Compuestos Epoxi/efectos adversos , Hiperpotasemia/inducido químicamente , Proteínas de Unión a Fosfato/efectos adversos , Polietilenos/efectos adversos , Diálisis Renal , Anciano , Calcio/sangre , Estudios de Casos y Controles , Compuestos Epoxi/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Unión a Fosfato/uso terapéutico , Fósforo/sangre , Poliaminas , Polietilenos/uso terapéutico , Potasio/sangre , Estudios Retrospectivos , Sevelamer , Factores de TiempoRESUMEN
PURPOSE OF REVIEW: Hyperphosphatemia in patients with end-stage renal disease leads to secondary hyperparathyroidism and renal osteodystrophy, and is independently associated with mortality risk. How hyperphosphatemia increases mortality risk is unknown but it may promote cardiovascular calcification. It is recommended that dialysis patients be treated to maintain normal serum phosphorus. Although calcium-based phosphate binders are cost-effective, their long-term safety has been questioned because of their postulated role in progression of cardiovascular calcification. In this regard, sevelamer hydrochloride has been recommended as an alternative phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders. RECENT FINDINGS: Results from the calcium acetate Renagel evaluation study indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorus and calcium x phosphorus product in hemodialysis patients. However, in the Treat-to-Goal study dialysis patients treated with sevelamer had less progression of coronary and aortic calcification than patients treated with calcium-containing binders. The mechanism underlying the slower rate of progression of cardiovascular calcification in sevelamer-treated patients remains uncertain but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol. SUMMARY: At present, evidence incriminating calcium-containing phosphate binders in the progression of cardiovascular calcification in end-stage renal disease remains largely circumstantial. As calcium acetate is more efficacious and cost-effective than sevelamer, it remains an accepted first-line drug. Treatment with sevelamer hydrochloride should be considered for patients with persistent hypercalcemia during calcium-based binder therapy despite appropriate adjustment of vitamin D therapy.