Etelcalcetide: injectable calcimimetic for the treatment of secondary hyperparathyroidism in hemodialysis-dependent patients.

Chronic kidney disease is associated with mineral and bone disorders that are now considered as a syndrome. One of the major complications of this syndrome is secondary hyperparathyroidism (SHPT). SHPT increases bone turnover and the risk of fracture. SHPT is also associated with cardiovascular calcification and high mortality risk. The classical medical therapies of SHPT lack long-term efficacy and have undesirable effects on serum calcium and phosphate levels. Surgical parathyroidectomy is a radical therapeutic solution potentially exposing patients to a permanent state of hypoparathyroidism among other complications. Oral cinacalcet revolutionized the treatment of SHPT because of its great efficacy; however, more than one-third of patients do not respond appropriately to cinacalcet, mostly because of intolerance and lack of compliance. Intravenous etelcalcetide improves medical adherence and reduces pill burden. It is 10-15% superior than cinacalcet in controlling parathyroid hormone, but also leads to more frequent episodes of hypocalcemia.

Integral pharmacological management of bone mineral disorders in chronic kidney disease (part II): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with costly complications and dismal hard-outcomes. AREAS COVERED: In two comprehensive articles we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (part 1) and hyperparathyroidism (this part 2), taking into account CKD-accelerated cardiovascular calcification (CVC) processes. EXPERT OPINION: Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.

Integral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.

INTRODUCTION: Chronic kidney disease-mineral and bone disorders (CKD-MBD), involving a triad of laboratory and bone abnormalities, and tissue calcifications, are associated with dismal hard-outcomes. AREAS COVERED: In two comprehensive articles, we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (this part 1) and hyperparathyroidism (part 2), taking into account CKD-accelerated atheromatosis/atherosclerosis and/or cardiovascular calcification (CVC) processes. EXPERT OPINION: Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.

Preoperative estimated glomerular filtration rate and the risk of major adverse cardiovascular and cerebrovascular events in non-cardiac surgery.

BACKGROUND: Chronic kidney disease is an independent predictor of perioperative cardiovascular morbidity and mortality. We analysed the preoperative estimated glomerular filtration rate (eGFR) as a risk factor for perioperative major adverse cardiovascular and cerebrovascular events (MACCE) in non-cardiac surgery. METHODS: In a post hoc analysis of the ANESCARDIOCAT database, patients were classified into six stages of eGFR calculated with the abbreviated Modification of Diet in Renal Disease Study and the Chronic Kidney Disease Epidemiology Collaboration equations: >90 (1), 60-89.9 (2), 45-59.9 (3a), 30-44.9 (3b), 15-29.9 (4), and <15 (5) ml min(-1) 1.73 m(-2). We analysed differences in MACCE, length of hospital stay, and all-cause mortality between eGFR stages. RESULTS: The eGFR was available in 2323 patients. Perioperative MACCE occurred in 4.5% of patients and cardiac-related mortality was 0.5%. Five hundred and forty-three (23.4%) patients had an eGFR of <60 ml min(-1) 1.73 m(-2) and 127 (5.4%) had an eGFR below 45 ml min(-1) 1.73 m(-2). Logistic regression analysis showed that MACCE increased with eGFR impairment (P<0.001), with a marked increase from stage 3b onwards (odds ratio 1.8 vs 3.9 in 3a and 3b, respectively, P=0.047). All-cause mortality was not related to eGFR (P=0.071), but increased substantially between stages 3b and 4. The length of stay correlated with eGFR (P<0.001). CONCLUSIONS: Perioperative MACCE increase with declining eGFR, primarily when <45 ml min(-1) 1.73 m(-2). We recommend the use of preoperative eGFR for cardiovascular risk assessment.

Clinical Uses of 1,25-dihydroxy-19-nor-vitamin D(2) (Paricalcitol).

The activation of vitamin D receptors (VDR) - (including activation by 25-hydroxyvitamin D) - seems to have not only mineral-metabolism beneficial effects but also important extra-skeletal actions. Paricalcitol is a synthetic vitamin D2 agonist of the VDR approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD). As a result of its selectivity, paricalcitol provides a wider therapeutic window for PTH suppression, minimizing deleterious effects of high serum calcium and/or phosphate concentrations. Paricalcitol also shares, and sometimes improves pleiotropic vitamin-D related systemic effects. For instance, paricalcitol has been repeatedly shown to decrease calcium and phosphate deposition in vessels and to decrease the expression of osteogenic factors preventing the active transformation of smooth muscle vascular cells into osteoblast-like cells in experimental models. In patients, paricalcitol has been associated with improved survival of dialysis patients and it may improve residual albuminuria in diabetic patients. Consequently, paricalcitol may enhance the standard of care in these high-risk patients. Although it seems reasonable to use these potential advantages to guide the individual and integral management of the complex CKD-mineral and bone disorder, it is necessary to recognize that many of these observations have not been proven nor confirmed in prospective clinical trials.

Role of vitamin D receptor activators in peritoneal dialysis.

Chronic kidney disease (CKD), including patients on peritoneal dialysis (PD), is linked to an important increase in mortality risk. Within the new systemic term CKD-MBD, alterations in vitamin D metabolism are also included. Many adverse events have been associated with vitamin D deficiency or lack of vitamin D receptor (VDR) activation both in the general population and CKD patients, and these associations seem to be maintained in PD patients. Particularities of PD in vitamin D metabolism, calcium balance, low PTH levels and the high prevalence of adynamic bone disease are discussed. We also review the associations of clinical or survival benefits with vitamin D supplementation, VDR or selective VDR activation, although they are low-graded and most of them obtained from HD databases. Nevertheless, we think that the combined approach to secondary hyperparathyroidism seems also to be appropriate in PD patients, and vitamin D (native plus VDR or selective VDR activation) seem an important part of the required integral approach. The later may provide additional benefits but definitive prove is still lacking.

Dietary and pharmacological control of calcium and phosphate metabolism in dialysis patients.

Chronic kidney disease-mineral and bone disorder is a new term defining a complex syndrome which underlines the need of a systemic approach to disturbances of calcium and phosphate metabolism in patients with renal failure. In recent years, the availability of new phosphorus binders and the appearance of new selective vitamin D receptor activators and calcimimetics have increased our current armamentarium and have changed previous paradigms. All these drugs can be used in combination, acting in distinct yet complementary pathways, with a resultant improvement in their individual clinical profile and reduction in secondary effects, while enhancing the achievement of clinical guideline targets. On the other hand, we should be aware that treatment costs are increasing and most of our knowledge is opinion-based. In this article, we shall consider rational recommendations on the control of calcium, phosphorus and parathyroid hormone while awaiting new evidence. We shall also briefly review some important related issues such as vascular calcification, adynamic bone disease, osteoporosis and the need of parathyroidectomy. Future guidelines may modify current recommendations, but we believe that the lack of an absolute evidence is not equivalent to the lack of awareness of the important problem which chronic kidney disease-mineral and bone disorder represents.

[Unawareness of the K/DOQI guidelines for bone and mineral metabolism in predialysis chronic kidney disease: results of the OSERCE Spanish multicenter-study survey]. / Desconocimiento de las guías K/DOQI sobre la alteración del metabolismo óseo-mineral asociada a la enfermedad renal crónica no en diálisis: resultados de la encuesta en el estudio multicéntrico español OSERCE.

Since its publication in 2003, the K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease (CKD) have become a worldwide reference. The aim of this study was to analyze the observance to these guidelines in patients with a glomerular filtration rate < 60 ml/min/1,73m2 not yet included in dialysis in a Spanish multicenter cohort. A questionnaire by investigator/centre was completed by 32 different nephrologists participating in the OSERCE study and representing the overall Spanish public health net. We observed that biochemical parameters were measured less frequently than recommended, except in CKD stage 3. The therapeutic goals for intact PTH were not properly reported by 59 % of the consulted nephrologists for stages 3 and 4, whereas only 22% did not report them properly for stage 5. The goals for phosphorus were not adequately reported in 50 % of cases (stages 3 y 4) and 60 % (stage 5). For calcium, these values were 70 %, 73.3 % and 65.5 % for stages 3, 4 and 5, respectively. A corrected plasma calcium between 9.5 and 10.2 mg/dl is still considered adequate for 31%. As much as 87% nephrologists stated that they did not sistematically measure calcidiol plasma levels. In general, these results demonstrate that there is a great degree of unawareness of K/DOQITM predialysis guidelines. Thus, their poor implementation is probably not only due to the lower availability of approved therapeutic agents, the difficult achievement of goals or the disbelief on current recommendations. It would be desirable that forthcoming guidelines such as the KDIGO could also consider the need of educational efforts for CKD-Mineral and Bone Disorder.

Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study.

BACKGROUND: Cinacalcet, a novel calcimimetic, simultaneously lowers parathyroid hormone (PTH), phosphorus (P), calcium (Ca) and Ca x P in patients who are on dialysis with secondary hyperparathyroidism (sHPT) associated with CKD. Previous studies have required cinacalcet to be administered during the dialysis session and at the same time on non-dialysis days. The aim of the SENSOR study was to demonstrate that cinacalcet given in a more clinically practical manner with the first major meal after dialysis is noninferior to cinacalcet given with food during the dialysis session. METHODS: In this open-label study dialysis patients with poorly controlled sHPT (intact PTH (iPTH) (3) 300 pg/ml) were randomized to receive cinacalcet either daily with their post-dialysis meal (n = 337) or with food during the dialysis session (n = 336). The primary endpoint was the proportions of patients with mean iPTH pound 300 pg/ml ( pound 31.8 pmol/l) at Weeks 11 and 13 of a 21-week treatment period. Secondary endpoints included the proportion of patients with Ca x P < 55 mg2/dl2 (< 4.44 mmol2/l2) at Weeks 11 and 13 and patients who discontinued the study due to nausea or vomiting. RESULTS: Comparable proportions of patients in the cinacalcet "during dialysis" and "post-dialysis meal" groups had a mean iPTH pound 300 pg/ml (54 vs. 57%, respectively, 95% confidence interval (CI) difference -4, +10%) and Ca x P < 55 mg2/dl2 (78 vs. 73%, respectively, 95% CI difference -11, +2%) at Weeks 11 and 13. The groups were also comparable at Week 21. Cinacalcet was well tolerated, with < 3% of patients in both groups discontinuing due to nausea or vomiting. A combined post-hoc analysis of both groups showed the incidence of nausea and vomiting was lower if cinacalcet was administered during the evening. CONCLUSIONS: Administering cinacalcet with the first main meal after dialysis was as effective as administration with food during the dialysis session. Cinacalcet was well tolerated. The incidence of gastrointestinal adverse events appeared to be lower when cinacalcet was administered in the evening.

[Tables estimating glomerular filtration rate from plasma creatinine]. / Tablas para la estimación del filtrado glomerular a partir de la creatinina plasmática.

Chronic kidney disease (CKD) and its related complications have become an important health and social problem. Very expensive resources are required in end-stage renal disease, and both complications of CKD as well as the important associated cardiovascular risk demand for interventions long before renal substitution therapies are needed. Thus, early diagnosis of CKD is currently considered of paramount importance, and it is based essentially upon the estimation of the glomerular filtration rate by formulae such as the abbreviated equation of the MDRD study. Nevertheless, in spite of international published recommendations, an automatic calculation to estimate the glomerular filtration rate (GFR) from serum creatinine is not reported by most laboratories yet and the need for creatinine assay standardisation is far from being implemented. Thus, we have designed some tables to show the creatinine value corresponding to different GFR for ages between 20 and 90 y/o, at 5 years intervals and in both sexes with both the MDRD-4 and MDRD-IDMS equations (Modification of Diet in Renal Disease-Isotope Dilution Mass Spectrometry). Moreover, we have created a global table including an estimation of GFR from plasma creatinine, age and sex by the MDRD-IDMS formula, the recommended for those laboratories which measure serum creatinine with assays aligned to the reference method. These tables aim to increase the awareness of the different assays for serum creatinine and to facilitate the diagnosis of CKD converting serum creatinine into GFR. This action should allow not only the early detection but also the possibility to establish the appropriate medical actions recommended after CKD detection.

Tablas para la estimación del filtrado glomerular a partir de la creatinina plasmática / Tables for estimating glomerular filtration rate from plasma creatinine

La enfermedad renal crónica (ERC) y las complicaciones que de ella se derivan se ha convertido en un importante problema social y sanitario, tanto por los recursos que se requieren en los estadios finales de la enfermedad como por las complicaciones secundarias a la propia ERC y a su elevado riesgo cardiovascular asociado. Hoy se considera de gran valor el diagnóstico precoz, basándose la definición y la clasificación actuales fundamentalmente en la estimación del filtrado glomerular (FG) por medio de fórmulas como la ecuación abreviada del estudio MDRD. No obstante, a pesar de las recomendaciones internacionales, no en todos los laboratorios es posible el cálculo automático del FG a partir de la creatinina plasmática ni se ha enfatizado la necesidad de estandarización de los métodos de medición de la misma. Es por ello que hemos diseñado unas tablas en las que se ha calculado el valor de creatinina correspondiente a los diferentes FG con significación clínica para cada una de las edades comprendidas entre 20y 90 años y a intervalos de 5 años en ambos sexos con lasfórmulas MDRD-4 y MDRD-IDMS (Modification of Diet in Renal Disease-Isotope Dilution Mass Spectrometry). Además hemos creado una tabla que integra de forma global una estimación del FG a partir de la creatinina plasmática por el método MDRD-IDMS que es el recomendado para aquellos laboratorios que utilizan un método de medición de la creatinina con trazabilidad respecto al método de referencia de espectrometría de masas por dilución isotópica. Estas tablas pretenden, no sólo incrementar la conciencia de la existencia de distintos ensayos en la medida de la creatinina sérica que influyen sobre la estimación del FG, sino también el facilitar el diagnóstico de la ERC a partir de la conversión de la creatinina plasmática en FG, para permitirá sí el diagnóstico precoz y el establecimiento de las acciones precisas que se recomiendan tras su detección (AU)

Chronic kidney disease (CKD) and its related complications have become an important health and social problem. Very expensive resources are required in end-stage renal disease, and both complications of CKD as well as the important associated cardiovascular risk demand for interventions long before renal substitution therapies are needed. Thus, early diagnosis of CKD is currently considered of paramount importance, and it is based essentially upon the estimation of the glomerular filtration rate by formulae such as the abbreviated equation of the MDRD study. Nevertheless, in spite of international published recommendations, an automatic calculation to estimate the glomerular filtration rate (GFR) from serum creatinine is not reported by most laboratories yet and the need for creatinine as say standardisation is far from being implemented. Thus, we have designed some tables to show the creatinine value corresponding to different GFR for ages between 20 and 90 y/o, at 5years intervals and in both sexes with both the MDRD-4 and MDRD-IDMS equations (Modification of Diet in Renal Disease-Isotope Dilution Mass Spectrometry). Moreover, we have created a global table including an estimation of GFR from plasma creatinine, age and sex by the MDRD-IDMS formula, the recommended for those laboratories which measure serum creatinine with assays aligned to the reference method. These tables aim to increase the awareness of the different assays for serum creatinine and to facilitate the diagnosis of CKD converting serum creatinine into GFR. This action should allow not only the early detection but also the possibility to establish the appropriate medical actions recommended after CKD detection (AU)

Documento de consenso: Recomendaciones sobre la utilización de ecuaciones para la estimación del filtrado glomerular en adultos / Recommendations for the use of equations to estimate glomerular filtration rate in adults

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Enfermedad cardiovascular en pacientes con enfermedad renal crónica: modelo experimental para la evaluación del eje cardio-renal / Cardiovascular disease in patients with chronic renal disease: an experimental model of the evaluation of the cardiorenal axis

El efecto de la alteración de la función renal sobre el incremento del riesgo cardiovascular ha sido demostrado en varios estudios. Los pacientes con enfermedad renal moderada a severa tienen un incremento exponencial de mortalidad y éste es fundamental de causa cardiovascular. En el presente trabajo se ha resumido la información de carácter experimental más revelante disponible y se acentúa la necesidad de contar con modelos animales de interacción cardiorrenal, para estudiar los factores interrelacionados

The effect of renal impairment on the increased cardiovascular risk has been demonstrated in several studies. Patients with mild to severe renal insufficiency show an exponential increase in mortality mainly derived from cardiovascular disease. In this article, we have summarized the information and the need for developing animal models of cardio-renal interaction, to study the involved interrelated factors

Larvas estériles como coadyuvantes al tratamiento local en una paciente con calcifilaxis proximal / Sterile maggots like coadjuvanted at the local treatment in a patient with proximal calciphylaxis

La calcifilaxis proximal con aparición de úlceras tiene una supervivencia muy pobre,siendo la infección la principal causa de la elevada mortalidad. Presentamos el caso deuna paciente diabética, obesa importante, en programa de hemodiálisis y diagnosticadade una calcifilaxis severa con grandes lesiones ulceradas en abdomen y muslo izquierdo.Tras un primer intento inefectivo de desbridamiento quirúrgico, al tratamiento médicosistémico se han asociado curas húmedas diarias con aplicación de pomadas enzimáticasy uso de larvas estériles que han resultado en una espectacular granulación yepitelización de estas úlceras. Queremos destacar las grandes propiedades desbridantes,desinfectantes y estimulantes para la cicatrización de las larvas estériles, pudiendoéstas constituir una muy buena terapia coadyuvante en las úlceras de la calcifilaxia, aúnsiendo éstas de localización proximal, previniendo la aparición de infección sistémica

Proximal calciphylaxis with skin ulcerations has a very poor survival and infection is themain cause of the high mortality rate.We present the case of a diabetic obese hemodialysiswoman diagnosed of severe calciphylaxis with extensive ulcers in the abdomen andleft thigh. After a first ineffective debridement attempt, systemic medical treatment was associatedwith daily wet cures with enzymatic ointments and maggot therapy resulting inspectacular granulation and healing of these ulcers.We want to underline the great propertiesof sterile maggots to selectively dissolve necrotic tissue, to disinfect the wound andto stimulate healing. Thus, sterile-maggot debridement may constitute a very good adjuvanttreatment even in proximal ulcers of calciphylaxis, preventing systemic infection

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

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.

[New therapeutic strategies in secondary hyperparathyroidism on dialysis (II): vitamin D analogues and calcium-mimetics]. / Nuevas estrategias terapéuticas para el hiperparatiroidismo secundario en diálisis (11): análogos de la vitamina D y calcimiméticos.

Secondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients. In this second article we will analyze the new vitamin D analogs, capable of decreasing parathyroid hormone (PTH) levels with a lower effect on intestinal calcium and phosphorus absorption. Among other advantages described in the experimental setting, paricalcitol shows a survival benefit in dialysis patients as compared to calcitriol, at least in retrospective studies, and thus it became our first-line vitamin D derivative. Calcimimetics are unique since they decrease PTH levels without increasing serum calcium and phosphorus. Actually, calcium and phosphorus decrease in a significant number of patients. These drugs will soon be authorized in Spain, and we describe the better achievement of K/DOQI guidelines as 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 bisphosphonates, the role of bone morphogenetic protein BMP-7, and the use of teriparatide. The future treatment of SHP will probably require the independent management of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combined treatments with selective drugs may prove more effective than sequential therapies.

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

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

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

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

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

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

Hemiparesia secundaria a hiponatremia severa de origen mixto / Hemiparesis secondary to hyponatremia

La hiponatremia es un trastorno electrolítico frecuente y su etiología es muy variada. En el período postoperatorio su aparición no es rara. Las causas más frecuentes en este contexto son el dolor, la sueroterapia hipotónica y en ocasiones el uso de diuréticos. Presentamos un caso de hiponatremia aguda severa con clinica neurológica en el postoperatorio de una nefroureterectomía derecha

Hyponatremia is a frequent electrolytic disorder of quite diverse aetiologies. It is not rare to find it during tbe postoperative period In this context its most frequent causes are pain, hypotonic serum therapy and, occasionally, the use of diuretics. We describe herein a case of severe acute hyponatremia with neurologic manifestations during tbe postoperative period after a right nephroureterectomy