Nuevas estrategias terapéuticas para el hiperparatiroidismo secundario en diálisis (I): nuevos conceptos, nuevos tratamientos / New therapy strategies in secondary hyperparathyroidism on dialysis (I): new concepts. New treatments

RESUMEN

El hiperparatiroidismo secundario (HPS) es una complicación frecuente y precozde la enfermedad renal crónica (ERC). La ERC es hoy un factor de riesgo cardiovascularindependiente y las alteraciones del metabolismo calcio-fósforo sonuno de sus factores inherentes modificables. En este primer artículo resumimos loscambios conceptuales recientes en pacientes en diálisis, derivados del reconocimientoy fisiopatología de la calcificación vascular, analizando las guías más actuales(K/DOQI), definiendo las implicaciones generales de la hiperfosfatemia ydescribiendo nuestra actitud terapéutica en relación a los captores del fósforo.Dada la atenuación de la progresión de la calcificación vascular y sus efectospleiotrópicos, consideramos el sevelamer como el captor de elección aunque aúnno haya demostrado una mejoría en la supervivencia, limitando en cualquier casoel uso de captores de calcio a 1.000-1.500 mg/día de calcio elemento. El carbonatode lantano es una importante alternativa terapéutica de futuro, especialmentesi se aclaran los problemas de seguridad relacionados con la potencial acumulacióndel metal. Las sales de hierro y los más recientes colestilán y nicotinamidapueden también jugar próximamente un papel. Del eficiente control del fósforo,con una sola droga o varias en combinación, depende hoy no sólo el éxito deltratamiento del HPS sino también el control de complicaciones graves asociadasa la diálisis

ABSTRACT

Secondary hyperparathyroidism (SHP) is still an early and frequent complicationof chronic renal disease (CRD). Currently, CRD is an independent cardiovascularrisk factor, and calcium-phosphorus metabolism is one of the modifiable relatedfactors. In this first article, we summarize the recent SHP treatment paradigmshift in dialysis patients, derived from the better knowledge and understanding ofvascular calcification. We analyze the most recent guidelines (K/DOQI), and describethe general implications of hyperphosphatemia, as well as our therapeuticapproach with phosphorus-binders. Since sevelamer additionally presents somepleiotropic effects and it attenuates the progression of vascular calcification, weconsider it in the first-line of treatment despite it is not yet demonstrated a survivalbenefit. We also minimize the use of elemental calcium to a maximum of 1,000to 1,500 mg/day. Lanthanum carbonate may well be an important therapeuticagent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play arole. All these drugs, isolated or in combination, are important in the treatment ofSHP since a great deal of its success and the avoidance of some dialysis-relatedcomplications depend on an efficient phosphorus controlSecondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients.In this second article we will analyze the new vitamin D analogs, capableof decreasing parathyroid hormone (PTH) levels with a lower effect on intestinalcalcium and phosphorus absorption. Among other advantages described in the experimentalsetting, paricalcitol shows a survival benefit in dialysis patients as comparedto calcitriol, at least in retrospective studies, and thus it became our firstlinevitamin D derivative. Calcimimetics are unique since they decrease PTH levelswithout increasing serum calcium and phosphorus. Actually, calcium and phosphorusdecrease in a significant number of patients. These drugs will soon be authorizedin Spain, and we describe the better achievement of K/DOQI guidelinesas well as other beneficial effects observed in the experimental animal with them.Finally, we mention the potential benefit of mild metabolic acidosis, the use of albisphosphonates,the role of bone morphogenetic protein BMP-7, and the use ofteriparatide. The future treatment of SHP will probably require the independentmanagement of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combinedtreatments with selective drugs may prove more effective than sequential therapies