Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up.

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary studies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad cardiovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p < 0.001). El mejor punto de corte fue de 5 (sensibilidad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Deterioro cognitivo sin demencia en la insuficiencia renal crónica terminal. datos de un centro argentino / Cognitive impairment without dementia in end-stage chronic renal disease. data from an argentinian center

RESUMEN Objetivos: Evaluar el desempeño cognitivo en una población hemodialítica. Conocer la relación entre la insuficiencias renal crónica terminal (IRCT) y la presencia de deterioro cognitivo, así como la influencia del tratamiento hemodialítico. Identificar otras variables que podrían influir en el desempeño cognitivo.Material y métodos:Estudio cuasiexperimental, de corte transversal. Se incluyeron 25 sujetos adultos, con IRCT en hemodiálisis. Grupo control compuesto por 4 sujetos sanos. Se registraron los antecedentes clínicos, información sobre diálisis y análisis de laboratorio. Se realizaron entrevistas individuales aplicando test Neuropsipor único operador. Resultados:El 36% de los pacientes presentaba alteraciones en atención y funciones ejecutivas, yel 24% presentaba alteración en memoria. Los pacientes con resultados alterados en atención y funciones ejecutivas eran de mayor edad y en mayor proporción mujeres, aunque sin significación estadística, además había porcentaje superior de HTA, cardiopatía isquémica y tabaquismo. Este grupo tenía niveles más bajos de hematocrito (32.11 ± 4.96 vs 35.69 ± 1.40, p=0.01) y hemoglobina (10.67 ± 1.55 vs 11.98 ± 0.51, P=<0.01), y tendencia a valores de colesterol total y triglicéridos más bajos. Los pacientes con resultados alterados en memoria presentaban mayor cantidad de episodios de hipotensión (5.83 ± 2.64 vs 2.63 ± 3.29; p=0.04), mayor proporción de pacientes con HTA (66.7% vs 26.3%; p=0.07) y niveles más bajos de hemoglobina (10.72 ± 1.75 vs 11.76 ± 0.84, P=0.05), sin presentar diferencias significativas respecto a niveles de metabolismo fosfocálcico, PTHi, albúmina, glucemia ni lípidos.Conclusiones: Los pacientes en hemodiálisis (HD) son una población de alto riesgo y con mayor prevalencia de trastornos cognitivos. Tanto las causas comórbidas, asociadas con enfermedad vascular crónica, como los trastornos de inflamación y malnutrición, son factores que se encuentran asociados a peores resultados.

ABSTRACT Objectives: To assess cognitive performance in a hemodialysis population. To know relationship between IRCT and the presence of cognitive impairment, as well as the influence of hemodialysis treatment. Identify other variables that could influence cognitive performance.Methods: quasi-experimental study design, cross section. 25 adult subjects with ESRD on hemodialysis were included. Control group consisted of 4 healthy subjects. Medicalhistories, information on dialysis and laboratory tests were recorded. Individual interviews were conducted using the Neuropsi test being performed by a single operator.Results: 36% of patients had alterations in attention and executive functions and 24% had impaired memory. Patients with abnormal results in attention and executive functions had older and proportion of women although not statistically significant, plus higher percentage of hypertension, ischemic heart disease and smoking. This group had lower levels of hematocrit (32.11 ± 4.96 vs 35.69 ± 1.40, p = 0.01) and hemoglobin (10.67 ± 1.55 vs 11.98 ± 0.51, P = <0.01) and a tendency to total cholesterol and lower triglycerides. Patients with abnormal results in memory had a greater number of episodes of hypotension (5.83 ± 2.64 vs 2.63 ± 3.29; p = 0.04), a higher proportion of patients with hypertension (66.7% vs 26.3%; p = 0.07) and more levels low hemoglobin (10.72 ± 1.75 vs 11.76 ± 0.84, P = 0.05); without significant differences in levels of calcium and phosphorus metabolism, PTH, albumin, glucose or lipids.Conclusions: HD patients are a high-risk population and higher prevalence of cognitive disorders. Both comorbid causes associated with chronic vascular disease and inflammation disorders and malnutrition are factors that are associated with worse outcomes.

High prevalence of secondary hyperparathyroidism in chronic kidney disease patients on dialysis in Argentina.

BACKGROUND: There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). OBJECTIVES AND METHODS: A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism. RESULTS: 1210 patients from 25 dialysis centres in Argentina participated in the study (representing 4.7% of the country's prevalent dialysis population in 2010). The mean patient age was 55.3±17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1% suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6 months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6% of patients had adequate levels of calcium (8.4-9.5 mg/dl), 51.6% had adequate phosphorus (3.5-5.5 mg/dl) and 21.1% displayed acceptable iPTH levels (150-300 pg/ml). 24% had iPTH <150 pg/ml and 54.5% >300 pg/ml. iPTH ≥600 pg/ml was present in 28.3%, and 13.3% had values ≥1000 pg/ml. These figures differed from those published by the DOPPS II study, in which 51.1% of patients had iPTH <150 pg/ml, and only 26.7% had iPTH ≥300 pg/ml. Calcium-based phosphate binders were used in 83.6% of the patients, 5.6% used sevelamer and 4.0% used aluminium-containing compounds. To achieve control of hyperparathyroidism, oral or intravenous calcitriol was predominantly used (50.5%) with a small percentage of patients receiving paricalcitol or doxercalciferol. CONCLUSIONS: The present study shows a high prevalence of secondary hyperparathyroidism, which differs from that published by other large population studies. There was a high proportion of patients with BMM markers outside the ranges suggested by K/DOQI. Mainly phosphate binders based on calcium and calcitriol continue to be used for the management of hyperphosphatemia and hyperparathyroidism respectively.

Elevada prevalencia de hiperparatiroidismo secundario en pacientes con enfermedad renal crónica en diálisis en Argentina / High prevalence of secondary hyperparathyroidism in chronic kidney disease patients on dialysis in Argentina

ANTECEDENTES: Existen pocos datos acerca de la prevalencia de los trastornos del metabolismo óseo y mineral (MOM) y su forma de manejo en pacientes con enfermedad renal crónica en Argentina. Objetivos y métodos: Mediante una encuesta realizada en 2010 en centros de diálisis, determinamos la prevalencia y las formas de tratamiento de los trastornos del MOM en Argentina y los comparamos con los datos publicados por otros grandes estudios poblacionales. Consignamos las características de los centros de diálisis y de los pacientes participantes, la frecuencia de las determinaciones y los resultados individuales de los marcadores bioquímicos del MOM y el tipo de manejo utilizado para controlar la hiperfosfatemia y el hiperparatiroidismo secundario. RESULTADOS: Participaron 1210 pacientes de 25 centros de diálisis de 10 provincias de Argentina (lo cual representaba el 4,7 % de la población prevalente en diálisis del país en 2010). La población estudiada tenía una edad media de 55,3 ± 17,6 años, 60,8 % eran varones, el 3,3 % en diálisis peritoneal y el 29,1 % eran diabéticos. El 100 % de los centros determinaban calcemia y fosfatemia mensualmente, el 60 % hormona paratiroidea intacta (PTHi) semestralmente, el 36 % cada 3 o 4 meses y el 4 % de forma anual. Según las recomendaciones de K/DOQI, el 51,6 % de los pacientes tenían niveles adecuados de calcio (8,4-9,5 mg/dl), el 51,6 % de fósforo (3,5-5,5 mg/dl) y el 21,1 % de PTHi (150 a 300 pg/ml). El 24,4 % tenían PTHi < 150 pg/ml y el 54,5 % > 300 pg/ml, con un 28,3 % con valores de PTHi > 600 pg/ml y un 13,3 % > 1000 pg/ml. Estos datos diferían de los publicados por el estudio DOPPS II, donde el 51,1 % de los pacientes presentaban PTHi < 150 pg/ml, y solo un 26,7 % PTHi > 300 pg/ml. El 83,6 % utilizaban un captor del fosfato basado en calcio, el 5,6 % sevelamer y el 4,0 % compuestos con aluminio. Para el control del hiperparatiroidismo se utilizaba predominantemente calcitriol oral o endovenoso (50,5 %), con un pequeño porcentaje de pacientes recibiendo paricalcitol o doxercalciferol. CONCLUSIONES: El presente estudio muestra una elevada prevalencia de hiperparatiroidismo secundario, lo cual difiere de lo publicado por otros grandes estudios poblacionales. Existe una elevada proporción de pacientes con marcadores del MOM por fuera de los niveles sugeridos por K/DOQI. Para el control de la hiperfosfatemia y el hiperparatiroidismo, se continúan utilizando mayormente captores del fosfato basados en calcio y calcitriol, respectivamente

BACKGROUND: There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). Objectives and methods: A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism. RESULTS: 1210 patients from 25 dialysis centres in Argentina participated in the study (representing 4.7% of the country's prevalent dialysis population in 2010). The mean patient age was 55.3±17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1% suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6 months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6% of patients had adequate levels of calcium (8.4-9.5mg/dl), 51.6% had adequate phosphorus (3.5-5.5mg/dl) and 21.1% displayed acceptable iPTH levels (150-300pg/ml). 24% had iPTH <150pg/ml and 54.5% >300pg/ml. iPTH >600pg/ml was present in 28.3%, and 13.3% had values >1000pg/ml. These figures differed from those published by the DOPPS II study, in which 51.1% of patients had iPTH <150pg/ml, and only 26.7% had iPTH >300pg/ml. Calcium-based phosphate binders were used in 83.6% of the patients, 5.6% used sevelamer and 4.0% used aluminium-containing compounds. To achieve control of hyperparathyroidism, oral or intravenous calcitriol was predominantly used (50.5%) with a small percentage of patients receiving paricalcitol or doxercalciferol. CONCLUSIONS: The present study shows a high prevalence of secondary hyperparathyroidism, which differs from that published by other large population studies. There was a high proportion of patients with BMM markers outside the ranges suggested by K/DOQI. Mainly phosphate binders based on calcium and calcitriol continue to be used for the management of hyperphosphatemia and hyperparathyroidism respectively