Implicaciones del metabolismo mineral en la morbimortalidad de los pacientes con enfermedad renal crónica avanzada

La alta prevalencia de calcificación vascular y de ateromatosis en la ERC justifica en parte, la elevada morbimortalidad cardiovascular. En esta tesis hemos analizado el valor predictor en morbimortalidad del conjunto de factores de riesgo tradicionales y del metabolismo mineral y el impacto de pruebas de imagen de calcificación vascular aorta -(IK) y de ateromatosis-(ecografía carotídea), junto con el ITB en una población con ERC sin diálisis El IK es el factor con mayor poder predictor sobre la incidencia de evento cardiovascular y mortalidad. El ITB es también un potente predictor de morbimortalidad. El cociente EFF/FGF23 refleja la resistencia renal fosfatúrica a la acción del FGF23. El umbral EFF/FGF23<1/3,9 cuadriplica el riesgo de calcificación severa y se confirma como el parámetro bioquímico mejor predictor de mortalidad global, superior al fósforo,FGF23 y EFF de manera aislada. El Klotho soluble plasmático, no mostró relación lineal con la edad ni con el FG.L'alta prevalença de calcificació vascular i d´ateromatosi a la MRC justifica en part, l'elevada morbimortalitat cardiovascular. En aquesta tesi hem analitzat el valor predictor de morbimortalitat del conjunt de factors de risc tradicionals i del metabolisme mineral i l'impacte de proves d'imatge de calcificació vascular aorta (IK) i d´ateromatosi (ecografia carotídia), juntament amb l'ITB en una població amb MRC sense diàlisi L´IK és el factor amb més poder predictiu sobre la incidència d'esdeveniment cardiovascular i mortalitat. L´ITB és també un potent predictor de morbimortalitat. El quocient EFF/FGF23 reflecteix la resistència renal fosfatúrica a l'acció del FGF23. El llindar EFF/FGF23 <1/3,9 quadruplica el risc de calcificació severa i es confirma com el paràmetre bioquímic millor predictor de mortalitat global, superior al fòsfor, FGF23 i EFF de manera aïllada. El Klotho soluble plasmàtic, no va mostrar relació lineal amb l'edat ni amb el FG.The high prevalence of vascular calcification and atheromatosis in CKD justified in part, the high cardiovascular morbidity and mortality. In this thesis we have analyzed the predictive value of mortality of all traditional risk factors and mineral metabolism and impact of vascular imaging of aortic calcification (KI) and atheromatosis (carotid ultrasound) with the ABI in a population with CKD not on dialysis. The KI is the factor most predictive power on the incidence of cardiovascular events and overall mortality. The ABI is also a powerful predictor of mortality. FEP/FGF23 ratio reflects the renal resistance to the action of FGF23. The FEP/FGF23 <1/3.9 threshold quadruples the risk of severe calcification and is confirmed as the best predictor of biochemical parameter overall mortality, than phosphate, FGF23 and FEP isolation. Plasma soluble Klotho, showed no linear relationship with age or glomerular filtration rate

A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe abdominal Aortic calcification in stage 3 and 4 kidney disease patients

Background: Vascular calcification (VC) contributes to high mortality rates in chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired phosphaturic response to FGF23 may affect VC. Therefore, their relative contribution to abdominal aortic calcification (AAC) was examined in patients CKD stages 3–4. Methods: Potential risk factors for AAC, measured by the Kauppila Index (KI), were studied in 178 patients. Results: In multivariate linear analysis, AAC associated positively with age, male gender, CKD-stage, presence of carotid plaques (CP) and also with FGF23, but negatively with fractional excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes with elevations in PTH, with reductions in GFR, and also with elevations in FGF23 but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic and zero-inflated analysis confirmed the independent association of age, CKD stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23 ratio of 1/3.9, below which the chances for a patient of presenting severe AAC increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios decreased from 1/1 to 1/3.9 but markedly increased in parallel with further reductions in FEP/FGF23 < 1/3.9. Conclusions: In CKD 3–4, an impaired phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC independently of age, gender or CP

Acute kidney failure secondary to very severe hypercalcaemia from primary hyperparathyroidism

La crisis hipercalcémica es una forma de presentación poco frecuente del hiperparatiroidismo primario. Solo existen pequeñas series de casos reportadas en la literatura1 and 2. Se caracteriza por hipercalcemia severa, insuficiencia renal y alteración del estado de conciencia. Presentamos el caso de un paciente de 70 años, que ingresa por fracaso renal agudo desencadenado por una crisis de hipercalcemia en el contexto de un hiperparatiroidismo primario no conocido previamente. Se discute la conducta terapéutica y la evolución del paciente

Result of the intervention “Education”: Diet prescribed in advanced chronic kidney disease

En la consulta de enfermedad renal crónica avanzada (ERCA), se proporcionan cuidados a los pacientes con enfermedad renal crónica con un filtrado glomerular (FG) < 30 ml/min. Estos incluyen diferentes intervenciones de enfermería. Una de ellas es la intervención 5614 Enseñanza: dieta prescrita. Objetivo: Analizar la eficacia de la intervención 5614 Enseñanza: dieta prescrita, en pacientes ERCA realizada en la consulta de enfermería, en la primera visita. Material y métodos: Estudio cuasiexperimental. Se incluyeron 92 pacientes incidentes en la consulta ERCA en 2014. Se realizó la intervención 5614 Enseñanza: dieta prescrita y se evaluaron indicadores de resultado 1004 Estado nutricional a los 2 meses de la intervención. Se llevó a cabo una estadística descriptiva de las variables pre y post intervención. Resultados: Edad media 69,5±15 años, 64,1% (n=59) hombres, 35,9% (n=33) mujeres, 41,3% diabéticos. Después de la intervención el 62% de los pacientes disminuyeron el valor del K, el 54,3% el del P, el 55,4% el del colesterol total, el 59,8% el del colesterol-LDL, y el 44,6% el del ácido úrico. El 67,4% de los pacientes presentó pérdida ponderal. En estos pacientes la variación media de la albúmina fue -0,005±0,0028 mg/dL. El FG permaneció estable en el 63% de los pacientes. La PAS media disminuye en el 42,4% de los pacientes y la PAD media en el 38%. Conclusiones: Tras la intervención 5614 Enseñanza: dieta prescrita realizada a los pacientes ERCA en la primera visita, se observa disminución del peso y valores plasmáticos de P, K, colesterol- LDL, colesterol total y ácido úrico. La Función renal permanece estable. La concentración de albúmina en los pacientes que perdieron peso se mantiene estable. La diferencia de la media para los valores de K y colesterol total fue estadísticamente significativa.Advanced chronic kidney disease (ACKD) units provide care to chronic kidney disease patients <30 ml/min glomerular filtration rate (GFR). These include different nursing interventions as 5614 intervention teaching: prescribed diet intervention. Goal: To analyze the effectiveness of 5614 Education: prescribed diet intervention in ACKD unit patients, on the first visit. Material and methods: Quasi-experimental study. 92 incident ACKD unit patients in 2014 were included. 5614 Teaching: prescribed diet intervention was performed. 1004 nutritional status outcome indicators were evaluated 2 months after nursing intervention. Descriptive statistics of the variables pre and post intervention was performed. Results: Mean age 69.5 ± 15 years, 64.1% (n = 59) men, 35.9% (n = 33) women, 41.3% diabetic. After nursing intervention, 62% of patients decreased the K values, 54.3% with P, 55.4% in total cholesterol, 59.8% in LDL-C, and 44.6% of uric acid. 67.4% of patients lost weight. In these patients the average variation of albumin was -0.005 ± 0.0028 mg /dL. The FG remained stable in 63% of patients. SBP mean decreased in 42.4% of patients and DBP mean in 38% patients. Conclusion: After 5614 Teaching: prescribed diet intervention at first ACKD unit visit weight loss and plasma levels of P, K, LDL-cholesterol, total cholesterol and uric acid were observed. Kidney function remained stable. Albumin concentration in patients who lost weight remained stable. The mean difference for the K values and total cholesterol was statistically significant

Predicting cardiovascular disease morbidity and mortality in chronic kidney disease in Spain. The rationale and design of NEFRONA: a prospective, multicenter, observational cohort study

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk (reverse epidemiology effect) and the presence of emerging risk factors specifically related to kidney failure. Therefore, diagnostic tools capable of improving cardiovascular risk assessment beyond traditional risk factors are currently warranted. We present the protocol of a 4-year prospective study aimed to assess the predictive value of non-invasive imaging techniques and biomarkers for CVD events and mortality in patients with CKD. Methods: From November 2009 to October 2010, 4137 asymptomatic adult patients with stages 2 to 5 CKD will be recruited from nephrology services and dialysis units throughout Spain. During the same period, 843 participants without CKD (control group) will be recruited from lists of primary care physicians, only at baseline. During the follow-up, CVD events and mortality will be recorded from all CKD patients. Clinical and laboratory characteristics will be collected in a medical documentation sheet. Three trained itinerant teams will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and measurement of ankle-brachial index. In CKD patients, presence and type of calcifications will be assessed in the wall of carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. From all participants, blood samples will be collected and stored in a biobank to study novel biomarkers. Conclusions: The NEFRONA study is the first large, prospective study to examine the predictive value of several non-invasive imaging techniques and novel biomarkers in CKD patients throughout Spain. Hereby, we present the protocol of this study aimed to explore the most effective way in which these tests can be integrated with traditional risk factors to maximize CVD detection in this population

High levels of hemoglobin promote carotid adventitial vasa vasorum neoangiogenesis in chronic kidney disease

Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients.This study was funded by the Health Institute Carlos III, Ministry of Economy and Competitiveness, Spain, Grants no. PI09/1999

Implicaciones del metabolismo mineral en la morbimortalidad de los pacientes con enfermedad renal crónica avanzada

La alta prevalencia de calcificación vascular y de ateromatosis en la ERC justifica en parte, la elevada morbimortalidad cardiovascular. En esta tesis hemos analizado el valor predictor en morbimortalidad del conjunto de factores de riesgo tradicionales y del metabolismo mineral y el impacto de pruebas de imagen de calcificación vascular aorta -(IK) y de ateromatosis-(ecografía carotídea), junto con el ITB en una población con ERC sin diálisis El IK es el factor con mayor poder predictor sobre la incidencia de evento cardiovascular y mortalidad. El ITB es también un potente predictor de morbimortalidad. El cociente EFF/FGF23 refleja la resistencia renal fosfatúrica a la acción del FGF23. El umbral EFF/FGF23<1/3,9 cuadriplica el riesgo de calcificación severa y se confirma como el parámetro bioquímico mejor predictor de mortalidad global, superior al fósforo,FGF23 y EFF de manera aislada. El Klotho soluble plasmático, no mostró relación lineal con la edad ni con el FG.L'alta prevalença de calcificació vascular i d´ateromatosi a la MRC justifica en part, l'elevada morbimortalitat cardiovascular. En aquesta tesi hem analitzat el valor predictor de morbimortalitat del conjunt de factors de risc tradicionals i del metabolisme mineral i l'impacte de proves d'imatge de calcificació vascular aorta (IK) i d´ateromatosi (ecografia carotídia), juntament amb l'ITB en una població amb MRC sense diàlisi L´IK és el factor amb més poder predictiu sobre la incidència d'esdeveniment cardiovascular i mortalitat. L´ITB és també un potent predictor de morbimortalitat. El quocient EFF/FGF23 reflecteix la resistència renal fosfatúrica a l'acció del FGF23. El llindar EFF/FGF23 <1/3,9 quadruplica el risc de calcificació severa i es confirma com el paràmetre bioquímic millor predictor de mortalitat global, superior al fòsfor, FGF23 i EFF de manera aïllada. El Klotho soluble plasmàtic, no va mostrar relació lineal amb l'edat ni amb el FG.The high prevalence of vascular calcification and atheromatosis in CKD justified in part, the high cardiovascular morbidity and mortality. In this thesis we have analyzed the predictive value of mortality of all traditional risk factors and mineral metabolism and impact of vascular imaging of aortic calcification (KI) and atheromatosis (carotid ultrasound) with the ABI in a population with CKD not on dialysis. The KI is the factor most predictive power on the incidence of cardiovascular events and overall mortality. The ABI is also a powerful predictor of mortality. FEP/FGF23 ratio reflects the renal resistance to the action of FGF23. The FEP/FGF23 <1/3.9 threshold quadruples the risk of severe calcification and is confirmed as the best predictor of biochemical parameter overall mortality, than phosphate, FGF23 and FEP isolation. Plasma soluble Klotho, showed no linear relationship with age or glomerular filtration rate