Nuevas estrategias terapéuticas para el hiperparatiroidismo secundario en diálisis (II): análogos de la vitamina D y calcimiméticos / New therapeutic strategies in secondary hyperparathyroidism on dialysis (II): vitamin d analogues and calcium-mimetics

RESUMEN

El hiperparatiroidismo secundario (HPS) sigue siendo una complicación frecuentedel paciente renal. En este segundo artículo se analizarán los análogos dela vitamina D capaces de disminuir la hormona paratiroidea (PTH) pero con menorefecto sobre la absorción de calcio y fósforo intestinal. Aparte de otras ventajasobservadas en el animal experimental, el paricalcitol ha demostrado una mejoríade la supervivencia en relación al calcitriol, al menos en estudios retrospectivos,por lo que lo consideramos el derivado de elección. Los calcimiméticos serán losúnicos fármacos capaces de disminuir la PTH sin inducir aumentos de calcio y/ofósforo séricos. De hecho en un porcentaje notable de estos pacientes, calcio yfósforo disminuyen. Pendientes de su incorporación al mercado español, se describela mejoría de cumplimiento de los objetivos de las guías y sus otros efectosbeneficiosos en el animal experimental. Finalmente se hace mención al potencialbeneficio de la acidosis metabólica leve, el uso de bisfosfonatos, el papel de laproteína morfogenética del hueso BMP-7 y la utilización de teriparatide. El futurode la terapia del HPS probablemente pasa por el manejo independiente de calcio,fósforo (P), vitamina D y PTH, de modo que los tratamientos combinados adosis bajas con drogas selectivas parecen más adecuados que las monoterapiassecuenciales

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