Persistent uncertainties in optimal treatment approaches of secondary hyperparathyroidism and hyperphosphatemia in patients with chronic kidney disease.

PURPOSE OF REVIEW: This review is a critical analysis of treatment results obtained in clinical trials conducted in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), hyperphosphatemia, or both. RECENT FINDINGS: Patients with CKD have a high mortality rate. The disorder of mineral and bone metabolism (CKD-MBD), which is commonly present in these patients, is associated with adverse outcomes, including cardiovascular events and mortality. Clinical trials aimed at improving these outcomes by modifying CKD-MBD associated factors have most often resulted in disappointing results. The complexity of CKD-MBD, where many players are closely interconnected, might explain these negative findings. We first present an historical perspective of current knowledge in the field of CKD-MBD and then examine potential flaws of past and ongoing clinical trials targeting SHPT and hyperphosphatemia respectively in patients with CKD.

Educación alimentaria en pacientes en dialisis / Nutritional education in dialysis patients

La enfermedad renal crónica terminal aumenta el riesgo cardiovascular y puede ocasionar defectos en la mineralización ósea. Para prevenir esto, se debe mantener el fósforo plasmático normal, que depende de la diálisis, los quelantes y la ingesta de fósforo, principalmente de origen inorgánico, incorporado mediante aditivos alimentarios. Las intervenciones nutricionales son pilares en el tratamiento de estos pacientes. El objetivo es facilitar estrategias alimentarias a un grupo de pacientes pediátricos en diálisis, mediante educación alimentaria nutricional, para aumentar el consumo de alimentos naturales, disminuyendo la ingesta de fósforo inorgánico especialmente de los productos cárnicos procesados. Materiales y métodos: se estudió una población pediátrica en diálisis. Se preparó un programa educativo con atención personalizada, instrucción alimentaria y seguimiento mensual, seguido de un taller. Resultados: n: 17 pacientes, edad decimal media de 12,3, 53% sexo masculino, 88% en hemodiálisis. Previo a la intervención el 64,7% consumía productos cárnicos procesados. Luego del taller el 58,8% disminuyó su consumo, el 41,2% aumentó la ingesta de preparaciones caseras, el 53% incorporó nuevos condimentos, de los cuales el 89% presentó al incorporarlos, mejor aceptación a las preparaciones. Conclusiones: la hiperfosfatemia está presente en alrededor del 50% de los pacientes en diálisis asociándose a un incremento entre 20% al 40% del riesgo de mortalidad. La presencia de fósforo oculto en los alimentos y la falta de adherencia hacen prioritario trabajar en programas educativos que favorezcan el aprendizaje colaborativo, centralizados en prácticas culinarias, para brindar herramientas que faciliten una alimentación natural, disminuyendo el consumo de ultraprocesados (AU)

Chronic end-stage renal disease increases the risk of cardiovascular disease and may lead to defects in bone mineralization. In order to prevent these risks, normal plasma phosphorus levels should be maintained. Achieving this goal depends on dialysis, chelators, and phosphorus intake, mainly of inorganic origin, incorporated through food supplements. Nutritional interventions are crucial in the treatment of these patients. The objective is to facilitate nutritional strategies to a group of pediatric dialysis patients, through food education, to increase the consumption of natural foods, decreasing the intake of inorganic phosphorus, especially from processed meat products. Materials and methods: a pediatric population undergoing dialysis was studied. An educational program was prepared with personalized care, nutritional instruction, and monthly follow-up visits, followed by a workshop. Results: n: 17 patients, mean age 12.3 years, 53% male, 88% on hemodialysis. Prior to the intervention, 64.7% consumed processed meat products. After the workshop, 58.8% decreased their consumption, 41.2% increased the intake of homemade food, 53% incorporated new seasonings, of whom 89% reported better acceptance of the preparations when they were incorporated. Conclusions: hyperphosphatemia is observed in around 50% of patients undergoing dialysis and is associated with a 20% to 40% increased risk of mortality. The presence of hidden phosphorus in food and the lack of adherence point to the need for the development of educational programs that promote collaborative learning, focusing on food-preparation practices. These programs should provide tools that facilitate a natural diet, reducing the consumption of ultra-processed food (AU)

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.

Sevelâmer para o tratamento da hiperfosfatemia em pacientes com doença renal crônica estágio 5D / Sevelamer for the treatment of hyperphosphatemia in patients with stage 5D chronic kidney disease

CONTEXTO: A doença renal crônica (DRC) é um problema de saúde pública crescente em todo o mundo, acompanhada de comorbidades muitas vezes mais graves do que a própria perda da função renal. Dentre elas, destacam-se os distúrbios do metabolismo ósseo e mineral (DMO), que levam à doença óssea e cardiovascular. Dessa forma, o DMO-DRC, além de poder resultar em fraturas, dor, deformidades ósseas e menor velocidade de crescimento nas crianças, também é fator de risco para calcificação vascular e associa-se a miocardiopatia e hipertrofia do ventrículo esquerdo, com consequente aumento do risco para doença cardíaca isquêmica, insuficiência cardíaca e morte de causa cardiovascular. Os mecanismos comuns entre a doença óssea e cardiovascular se apoiam nas crescentes evidências de que alterações na remodelação óssea favorecem o desenvolvimento de calcificações extra ósseas, principalmente vasculares. As alterações no metabolismo mineral e ósseo são frequentes na DRC, observadas já nos estágios iniciais da DRC, quando a taxa de filtração glomerular está em

Fibrous osteodystrophy due to secondary renal hyperparathyroidism in a senile dog / Osteodistrofia fibrosa decorrente de hiperparatireodismo secundário renal em cão senil

Renal hyperparathyroidism stands out among the complications of kidney disease in dogs due to phosphorus retention with a predisposition to hypocalcemia, parathyroid hormone stimulation with mobilization of calcium from the bones, characterizing fibrous osteodystrophy, unusual in the elderly. The objective was to report it in 12-year-old Labrador with polyuria, polydipsia, and emesis for five months due to maxillary and mandibular volume increase, followed by loosely fixed teeth, and facial deformity. Blood tests showed anemia, thrombocytosis, azotemia, hypoalbuminemia and hyperphosphatemia and urinalysis showed low density, glycosuria, proteinuria, and moderate caudate and transitional epithelial cells. Oral x-rays showed loss of dental bone support and decreased bone radiopacity. Chest radiographs showed decreased density in the ribs and costochondral junction; on the other hand, organs of the cardiorespiratory system showed no changes. The electrocardiogram and echocardiogram did not show impairment. Abdominal ultrasound revealed kidneys with asymmetry, increased echogenicity of the cortical and poorly preserved cortico-medullary definition. Oral histopathology showed intense fibroplasia associated with bone reabsorption. Support therapy was instituted, but the patient died ten days after consultation. Thus, although uncommon in the elderly, fibrous osteodystrophy should be investigated in dogs with advanced-stage chronic kidney disease and, even with conservative therapies, the prognosis is unfavorable.

O hiperparatireoidismo renal destaca-se entre as complicações da doença renal em cães, pela retenção de fósforo com predisposição à hipocalcemia, estimulação de paratormônio com mobilização do cálcio dos ossos, caracterizando a osteodistrofia fibrosa, incomum em idosos. O objetivo foi relatá-la em Labrador de 12 anos com poliúria, polidipsia e vômitos há cinco meses, além de aumento de volume maxilar e mandibular seguido de dentes frouxamente fixados e deformidade facial. Os exames sanguíneos denotaram anemia, trombocitose, azotemia, hipoalbuminemia, hiperfosfatemia, urinálise, baixa densidade, glicosúria, proteinúria e moderadas células caudadas e epiteliais de transição. Pelos raios X orais, houve perda da sustentação óssea dentária e diminuição da radiopacidade óssea. As radiografias de tórax demonstraram diminuição da densidade óssea na região dos arcos costais e junção costocondral; em contrapartida, órgãos do sistema cardiorrespiratório se mostraram sem alterações aparentes. O eletrocardiograma e o ecocardiograma não incidiram comprometimento. O ultrassom abdominal revelou rins com assimetria, aumento da ecogenicidade cortical e definição corticomedular pouco preservada, e a histopatologia oral apontou intensa fibroplasia associada à reabsorção óssea. Foi instituída terapia suporte, mas o paciente veio a óbito 10 dias após a consulta. Assim, mesmo que incomum em idosos, a osteodistrofia fibrosa deve ser investigada em cães com doença renal crônica em estágio avançado, mesmo com as terapias conservadoras, o prognóstico é desfavorável.

Clinical and nutritional follow-up of cats with chronic kidney disease fed with a renal prescription diet

Background: The use of prescription diets for cats with chronic kidney disease (CKD) is one of the main managementapproach of this disease in cats, and is considered a renoprotective strategy that may promote increased survival and/orimprove quality of life, according to the stage of CKD. Besides that, nutritional assessment is important to monitor themaintenance of quality of life of the patients and their response to disease, especially those with chronic conditions. Theaim of this study was to follow the clinical and nutritional status of cats with chronic kidney disease (CKD) IRIS stagesII, III and IV fed with a renal prescription diet, followed for 12 months.Materials, Methods & Results: Patients were fed exclusively with a dry renal prescription diet and medications for themanagement of CKD were prescribed when needed. Exclusion criteria were cats that already received a renal prescriptiondiet or medications for the treatment of CKD. Cats were evaluated every 2 months, considering body weight (BW), bodycondition score (BCS), muscle mass score (MMS), clinical and laboratory parameters. In all assessments, a complete bloodcount and biochemistry were performed by conventional methods with the patient fasted for 12 h. In addition, urinalysis,urine protein:creatinine ratio (UPC) and urine culture were performed from a urine sample collected by cystocentesis.The quantitative variables were tested for their stability on consecutive assessments using the non-parametric Friedmantest, and did not present significant variation during follow-up, except for systolic blood pressure (SBP). Eight cats witha diagnosis of CKD were included in the study and 6 of them remained in the same CKD stage during follow-up. On catdied due to an unrelated CKD cause. Regarding nutritional assessment, 5 of 7 cats maintained BW during the 12 months...(AU)

Clinical and nutritional follow-up of cats with chronic kidney disease fed with a renal prescription diet

Background: The use of prescription diets for cats with chronic kidney disease (CKD) is one of the main managementapproach of this disease in cats, and is considered a renoprotective strategy that may promote increased survival and/orimprove quality of life, according to the stage of CKD. Besides that, nutritional assessment is important to monitor themaintenance of quality of life of the patients and their response to disease, especially those with chronic conditions. Theaim of this study was to follow the clinical and nutritional status of cats with chronic kidney disease (CKD) IRIS stagesII, III and IV fed with a renal prescription diet, followed for 12 months.Materials, Methods & Results: Patients were fed exclusively with a dry renal prescription diet and medications for themanagement of CKD were prescribed when needed. Exclusion criteria were cats that already received a renal prescriptiondiet or medications for the treatment of CKD. Cats were evaluated every 2 months, considering body weight (BW), bodycondition score (BCS), muscle mass score (MMS), clinical and laboratory parameters. In all assessments, a complete bloodcount and biochemistry were performed by conventional methods with the patient fasted for 12 h. In addition, urinalysis,urine protein:creatinine ratio (UPC) and urine culture were performed from a urine sample collected by cystocentesis.The quantitative variables were tested for their stability on consecutive assessments using the non-parametric Friedmantest, and did not present significant variation during follow-up, except for systolic blood pressure (SBP). Eight cats witha diagnosis of CKD were included in the study and 6 of them remained in the same CKD stage during follow-up. On catdied due to an unrelated CKD cause. Regarding nutritional assessment, 5 of 7 cats maintained BW during the 12 months...

Nutritional Guideline for the Management of Mexican Patients with CKD and Hyperphosphatemia.

Chronic kidney disease (CKD) represents a serious concern for the Mexican population since the main predisposing diseases (diabetes, hypertension, etc.) have a high prevalence in the country. The development of frequent comorbidities during CKD such as anemia, metabolic disorders, and hyperphosphatemia increases the costs, symptoms, and death risks of the patients. Hyperphosphatemia is likely the only CKD comorbidity in which pharmaceutical options are restricted to phosphate binders and where nutritional management seems to play an important role for the improvement of biochemical and clinical parameters. Nutritional interventions aiming to control serum phosphate levels need to be based on food tables, which should be specifically elaborated for the cultural context of each population. Until now, there are no available food charts compiling a high amount of Mexican foods and describing phosphorus content as well as the phosphate to protein ratio for nutritional management of hyperphosphatemia in CKD. In this work, we elaborate a highly complete food chart as a reference for Mexican clinicians and include charts of additives and drug phosphate contents to consider extra sources of inorganic phosphate intake. We aim to provide an easy guideline to contribute to the implementation of more nutritional interventions focusing on this population in the country.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

Recomendaciones para el manejo de la lisis tumoral / Recommendations for tumor lysis syndrome management

El síndrome de lisis tumoral representa una complicación potencialmente letal provocada por la liberación masiva de ácidos nucleicos, potasio y fosfato hacia la circulación como resultado de la lisis de células neoplásicas, las cuales se caracterizan por una rápida capacidad de proliferación y alta sensibilidad a fármacos. Esto puede ocurrir de forma espontánea antes del inicio del tratamiento y agravarse luego de haberse iniciado la quimioterapia. Presenta una alta mortalidad. Su prevención continúa siendo la medida terapéutica más importante. El cuadro clínico se caracteriza por la existencia de trastornos del metabolismo hidroelectrolítico, en particular, hipercalemia, hiperfosfatemia e hiperuricemia y por la aparición de una lesión renal aguda. Una adecuada intervención terapéutica implica hidratación intravenosa y medidas para prevenir o corregir las alteraciones metabólicas. En este artículo, se proponen lineamientos para seguir tanto en la etapa diagnóstica como en el tratamiento de esta complicación.

The tumor lysis syndrome represents a potentially lethal complication caused by the massive release of nucleic acids, potassium and phosphate into the circulation as a result of the lysis of neoplastic cells, which are characterized by a rapid proliferation capacity and high sensitivity to drugs. This may occur spontaneously prior to the start of treatment, becoming worse after the initiation of chemotherapy. It presents a high mortality; its prevention continues being the most important therapeutic measure. The clinical picture is characterized by the existence of hydroelectrolytic metabolism disorders, in particular hyperkalemia, hyperphosphatemia and hyperuricemia and by the appearance of an acute renal lesion. Adequate therapeutic intervention involves intravenous hydration and measures to prevent or correct metabolic alterations. This article proposes guidelines to follow both in the diagnostic stage and in the treatment of this complication.

Carbonato de sevelamer para control de la hiperfosfatemia en la insuficiencia renal crónica / Sevelamer carbonate for the control of hyperphosphatemia in chronic kidney failure

CONTEXTO CLÍNICO: La enfermedad renal crónica (ERC) se asocia a una elevada morbimortalidad; siendo las patologías cardiovasculares una de las causas más importante de muerte sumado a la existencia de múltiples factores de riesgo no clásicos inherentes a la propia enfermedad, como la anemia, albuminuria, inflamación, estrés oxidativo, malnutrición, entre otros. Las alteraciones del metabolismo óseo-mineral hoy en día son consideradas un componente importante de estos factores de riesgo cardiovascular no tradicionales en los pacientes con ERC. La hiperfosfatemia y el aumento de factor de crecimiento fibroblástico (FGF-23) son los parámetros más importantes, por encima incluso de la hormona paratiroidea (PTH), calcio plasmático (CA) o fosfatasa alcalina (FAL) que se asocian a la mortalidad de pacientes dializados. TECNOLOGÍA: El carbonato sevelamer es una molécula con numerosas aminas separadas por un carbono del esqueleto del polímero que se cargan parcialmente de protones en el estómago. Estas aminas protonadas se unen en el intestino a iones con carga negativa como el fósforo de la dieta disminuyendo así la absorción del mismo. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de carbonato de sevelamer para control de hiperfosfatemia en la insuficiencia renal crónica. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron dos RS, tres GPC, dos evaluaciones económicas y 14 informes de políticas de cobertura para el uso de carbonato de sevelamer en hiperfosfatemia para ERC. CONCLUSIONES: Evidencia de baja calidad sugiere que el uso de carbonato de sevelamer reduciría la mortalidad por todas las causas a corto plazo, y disminuiría la hiperfosfatemia en pacientes que requieren reemplazo de la función renal y que no han respondido a terapia con quelantes cálcicos. Evidencia de muy baja calidad no permite establecer el efecto sobre la mortalidad cardiovascular ni que alguno de los quelantes de fósforo sea superior a alternativas en cuanto a disminuir los niveles de fósforo o presentar menor frecuencia de efectos adversos como constipación o intolerancia digestiva. Las distintas guías de práctica clínica relevadas, como la guía KDIGO, así como otras latinoamericanas y argentinas recomiendan en forma genérica el uso de quelantes no cálcicos en alguna de las siguientes situaciones: pacientes que hubieren alcanzado dosis máximas de quelante cálcico con niveles de fósforo no controlado; pacientes con calcemia corregida mayor de 10 mg/dL a pesar de estar dializando con un calcio de 2,5 mEq/L; pacientes con una hiperfosfatemia persistente y sostenida mayor o igual a 6,5 mg/dL; pacientes con calcificaciones vasculares y/o calcifilaxis. En pacientes en estadios pre-dialíticos sólo debería indicarse en el caso de hiperfosfatemia progresiva o persistente por más de tres meses que no responde, y no para prevenir hiperfosfatemia. Diversos financiadores de salud estadounidenses, europeos, latinoamericanos y argentinos cubren el carbonato de sevelamer para el tratamiento de hiperfosfatemia sin establecer criterios definidos en algunos casos y en otros según las recomendaciones de distintas guías de práctica clínica.

Non-adherence to Haemodialysis, Interdialytic weight gain and cardiovascular mortality: a cohort study.

BACKGROUND: Patients with chronic kidney diseases (CKD) on haemodialysis (HD) have high morbidity and mortality rates, which are also due to the inherent risks associated with nephropathy. Non-adherence (NA) to the different demands of the treatment can have consequences for the outcome of patients undergoing HD; nevertheless, there are still doubts about such repercussions. This study was conducted to evaluate the association between NA to conventional HD and all-cause mortality and cardiovascular mortality. METHODS: We prospectively evaluated mortality in a 6-year period in a cohort of 255 patients on HD in northeast Brazil. The evaluated parameters of NA to HD were interdialytic weight gain (IDWG) ≥ 4% of dry weight (DW), hyperphosphatemia and regular attendance at treatment, assessed as the correlation between the periods on HD completed and those prescribed. We used the Cox multivariate regression model to analyse survival and the predictors of all-cause mortality and cardiovascular mortality. RESULTS: With a median follow-up period of 1493 days and a mortality rate of 9.1 per 100 people-years, there were 87 deaths, of which 54% were cardiovascular deaths. IDWG ≥4% of DW was associated with a risk of all-cause mortality however presenting a borderline outcome for cardiovascular mortality, with hazard ratios of 2.02 (CI 95% 1.17-3.49, p = 0.012) and 2.09 (CI 95% 1.01-4.35, p = 0.047), respectively. No significant association was found between other parameters of NA and mortality. Subgroup analysis showed that for patients with IDWG ≥4% of DW, malnutrition, age and diagnosis of cardiovascular and cerebrovascular diseases were associated with higher all-cause mortality. CONCLUSIONS: IDWG ≥4% of DW was identified as an independent predictor of all-cause mortality and demonstrated a borderline outcome for cardiovascular mortality in patients on conventional HD. The occurrence of excessive IDWG in the presence of malnutrition represented a significant increase in the risk of death, indicating a subgroup of patients with a worse prognosis.

The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism / Impacto de cinacalcete em marcadores do metabolismo mineral de pacientes em diálise portadores de hiperparatireoidismo secundário grave

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Resumo Introdução: O tratamento do hiperparatireoidismo secundário (HPTs), patologia comum e associada à mortalidade na doença renal crônica, é um desafio para o nefrologista. Advento dos calcimiméticos propiciou terapêutica medicamentosa diferente da usual, baseada em quelantes de fósforo e vitamina D ativa. O objetivo deste estudo foi avaliar segurança e efetividade de cinacalcete no controle do HPTs grave de pacientes em diálise crônica. Métodos: Estudo retrospectivo 26 pacientes [idade: 52 ± 12 anos; 55% mulheres; tempo em diálise: 54 (4-236) meses], em hemodiálise (N = 18) ou diálise peritoneal (N = 8), com HPTs grave (nível de paratormônio intacto (PTHi) > 600 pg/mL), com hiperfosfatemia e/ou hipercalcemia persistentes, em tratamento com cinacalcete. Período de seguimento de 12 meses. Avaliados níveis séricos de cálcio (Ca), fósforo (P), fosfatase alcalina (FA) e PTHi no início do seguimento, 30, 60, 90, 180 e 365 dias. Resultados: Indicações para início do cinacalcete: hiperfosfatemia (57,7%), hipercalcemia (23%), ou ambos (19,3%) com PTH > 600 pg/mL. Ao final do seguimento, observada redução dos níveis PTHi (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0,001), Ca (9,5 ± 1,0 vs. 9,1 ± 0,6 mg/dl; p = 0,004), P (6,0 ± 1,3 vs. 4,9 ± 1,1 mg/dl; p < 0,001) e FA (202 ± 135 vs. 155 ± 109 UI/L; p = 0,006). Eventos adversos: hipocalcemia (26%) e queixas digestivas (23%). No fim do estudo, 73% pacientes utilizavam vitamina D ativada associada ao cinacalcete. Três (11,5%) pacientes, todos em DP, não responderam ao cinacalcete, mantendo níveis PTHi > 800 pg/mL. Conclusão: Utilização de cinacalcete, associado à terapia tradicional, em pacientes com HPTs grave foi segura, eficiente e associada a melhor controle do metabolismo mineral.

The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism.

INTRODUCTION: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. METHODS: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. RESULTS: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. CONCLUSION: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Hiperfosfatasemia transitoria benigna de la infancia, reporte de un caso / Benign transient hyperphosphatasemia of childhood: a case report

La Hiperfosfatasemia Transitoria Benigna (HTB) es la causa más frecuente de elevación aislada de la Fosfatasa Alcalina (FA) en la población pediátrica. Es relevante tener la sospecha de esta entidad dada su frecuencia, carácter auto limitado y fácil diagnóstico, a pesar de esto, es poco conocida y estudiada en la Pediatría. Su clínica se asocia a niños sanos como a infecciones virales respiratorias, gastrointestinales y al retraso ponderal. El presente trabajo tiene como objetivo reportar un caso clínico y revisar el diagnóstico de la HBT.

Benign Transient Hyperphosphatasemia (BTH) is the most frequent cause of isolated elevation of Alkaline Phosphatase (AF) in the pediatric population. It is relevant to have the suspicion of this entity given its frequency, self limited character and easy diagnosis, despite this, it is little known and studied in Pediatrics. Its symptoms are associated with healthy children, such as viral respiratory, gastrointestinal infections and delayed weight gain. The objective of this work is to report a clinical case and review the diagnosis of HBT.

Seudohipoparatiroidismo 1b / Pseudohypoparathyroidism 1b

RESUMEN El seudohipoparatiroidismo 1b se caracteriza por resistencia aislada a la parathormona, en ausencia de las manifestaciones típicas de la osteodisfrofia hereditaria de Albright; debido a alteraciones epigenéticas del locus GNAS. Puede presentarse de forma esporádica, o heredado de manera autosómico dominante por vía materna. Se presenta paciente masculino de 31 años, con antecedentes de tumores óseos y calcificaciones cerebrales diagnosticados a los 14 años; que se consulta por presentar mareo intenso, rigidez del cuello y la boca, dificultad para hablar y tragar, desorientación y trastornos de percepción; con fenotipo y somatometría normales, y signos de tetania latente (Chvostek y Trouseau positivos). Los estudios realizados mostraron: hipocalcemia, hiperfosfatemia, aumento de niveles de parathormona y múltiples calcificaciones en cerebro y cerebelo. Con tales hallazgos se emite el diagnóstico de seudohipoparatiroidismo 1b, el cual se confirma mediante pruebas moleculares con alteración en el patrón de metilación en el locus GNAS. No presentó alteraciones en el estudio de secuenciación de los 13 exones codificantes del GNAS. Se concluyó como un caso esporádico ante la ausencia de historia familiar de hipocalcemia, combinado con amplia pérdida de metilación del gen GNAS y la no evidencia de deleciones. Se presenta el primer reporte de esta enfermedad en Cuba con estudio molecular(AU)

ABSTRACT Pseudohypoparathyroidism 1b is characterized by isolated resistance to parathormone, in the absence of the typical manifestations of hereditary Albright osteodysphrophy; due to epigenetic alterations of the GNAS locus. It can occur sporadically, or inherited in an autosomal dominant way through the mother. We report the case of a 31-year-old male patient, with history of bone tumors and cerebral calcifications diagnosed at age 14. She came to consultation due to severe dizziness, stiff neck and mouth, difficulty speaking and swallowing, disorientation and perception disorders; he showed normal phenotype and somatometry, and signs of latent tetany (positive Chvostek and Trouseau). Studies have shown hypocalcaemia, hyperphosphatemia, increased levels of parathormone and multiple calcifications in the brain and cerebellum. These findings, pseudohypoparathyroidism 1b is diagnosed confirmed by molecular tests showing alteration in the methylation pattern in the GNAS locus. There were no alterations in the sequencing study of the 13 exons coding for GNAS. It was concluded as a sporadic case in the absence of a family history of hypocalcemia, combined with extensive loss of GNAS gene methylation and no evidence of deletions. This is the first report this disease with molecular study in Cuba(AU)

Effectiveness of sucroferric oxyhydroxide in patients on on-line hemodiafiltration in real-world clinical practice: A retrospective study / Eficácia do oxihidróxido sucroférrico em pacientes em hemodiafiltração on-line na realidade da prática clínica: um estudo retrospectivo

Abstract Introduction: Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group. Objective: To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden. Methods: A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO. Results: A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment. Conclusion: During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.

Resumo Introdução: A hiperfosfatemia é uma grave consequência da doença renal crônica associada a risco aumentado de doença cardiovascular. O controle dos níveis séricos de fósforo dos pacientes em diálise é um desafio que requer, na maioria dos casos, o uso de quelantes de fosfato (QF). Parte da dificuldade se deve à baixa adesão ao tratamento oriunda do grande número de medicamentos receitados para esse grupo de pacientes. Objetivo: Avaliar a real eficácia do oxihidróxido sucroférrico (OHS) no controle dos níveis séricos de fósforo e determinar a carga de comprimidos associada. Métodos: Estudo multicêntrico, quantitativo, retrospectivo, antes e depois conduzido com pacientes em hemodiafiltração on-line. Pacientes remanejados para OHS como parte dos cuidados de rotina foram incluídos no estudo. Tratamento com QF, número de comprimidos, níveis séricos de fósforo, reposição férrica endovenosa e dosagens foram registrados mensalmente durante seis meses de tratamento com QF ou OHS. Resultados: Foram incluídos 42 pacientes no estudo. Após a mudança de QF para OHS, o número de comprimidos prescritos por dia caiu em 67%, de seis para duas unidades diárias (p < 0,001). A frequência de ingestão de comprimidos caiu de três para duas vezes ao dia (p < 0,001). Durante o tratamento com OHS, o percentual de pacientes com fósforo sérico ≤ 5,5 mg/dL aumentou de 33,3% no início para 45% após seis meses de tratamento. Conclusão: Durante os seis meses de seguimento com OHS, os níveis séricos de fósforo foram controlados com um terço dos comprimidos por dia em relação aos tratamentos com outros QF.