Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta.

Hipovitaminosis D en pacientes hemodiálizados (HD): factores relacionados e influencia sobre la fuerza muscular / Hypovitaminosis D in patients on hemodialysis (HD): related factors and influence on muscle strength

Introducción: La deficiencia de 25 (OH) vitamina D es una alteración prevalente en los pacientes con enfermedad renal crónica (ERC) , sin embargo en nuestro medio no es medida de manera rutinaria y por ende no suele hacerse reposición vitamínica. Nuestro objetivo fue determinar la prevalencia y los factores relacionados a deficiencia de 25 (OH) D en pacientes con ERC en hemodiálisis (HD), particularmente la relación con la función y masa muscular. Métodos: Efectuamos un estudio prospectivo, multicéntrico, en pacientes adultos en HD crónica que no estuvieran recibiendo ningún derivado de la vitamina D. Se midieron en sangre los niveles de 25(OH) D, Hemoglobina, PCR, Albúmina, Ca, P, FAL, PTHi. Se realizó la medición de la fuerza del puño con dinamómetro, y la prueba de sentado-parado. Se aplicó el índice de Karnofsky para clasificar el estado funcional., Se realizó una bioimpedanciometría (BCM; Frese nius Medical Care) en aquellos pacientes sin, contraindicación. Resultados: Se incluyeron 138 pacientes. La 25(OH) vitamina fue de 20.43 ± 10.5 ng/ml, la prevalencia de insuficiencia /defi ciencia 87% (37% con menos de 15 ng/ml). Las concentraciones de vitamina D/deficiencia mostraron correlación/relación significativa con la edad, la presencia de diabetes, los niveles de hemoglobina y albúmina, la fuerza y la masa muscular y la clase funcional (p<0.05) . Conclusión: Alta prevalencia de hipovitaminosis D en pacientes hemodializados particularmente gerontes y diabéticos. Esto estaría relacionado con la desnutrición, anemia, clase funcional y la fuerza/masa muscular de los pacientes, estos últimos dos factores no reportados hasta ahora. Todos estos factores deben ser considerados al momento de la sustitución vitamínica y en la evaluación de la efectividad de la misma.

Background: 25 (OH) vitamin D deficiency is a prevailing alteration in patients with chronic kidney disease (CKD); however, in our environment, it is not routinely measured and, therefore, vitamin replacement is unusual. Our purpose was assessing the prevalence of and the factors related to 25 (OH) vitamin D deficiency in patientswith CKD in hemodialysis (HD), especially the relation to function and muscle mass. Methods: We conducted a prospective, multicenter study in adult patients on chronic HD who were not receiving any vitamin D derivative. Blood levels of 25 (OH) D, Hemoglobin, CRP, Albumin, Ca,P, ALP and PTHi were measured. The handgrip strength was measured with a dynamometer and the sitting-rising test was carried out. A bioimpedance analysis (BCM; Fresenius Medical Care) was conducted in the patients who had no contraindications. Results: 138 patients were included. The levels of 25 (OH) vitamin D were 20.43±10.5 ng/ml; the insufficiency/deficiency had 87% prevalence (and 37% prevalence with less than 15 ng/ml). Vitamin D concentrations/ deficiency showed a significant correlation with/ relation to age, diabetes, hemoglobin and albumin levels, muscle strength and mass, and functional class (p<0.05). Conclusion: High prevalence of hypovitaminosis D in patients on hemodialysis, particularly in the elderly and in patients with diabetes. This should be related to undernutrition, anemia, the functional class and the muscle strength/mass of patients, the latter two being unreported factors until now. All these factors should be considered when vitamin replacement is conducted and when its effectiveness is assessed.

Hipovitaminosis D en pacientes hemodiálizados (HD): factores relacionados e influencia sobre la fuerza muscular / Hypovitaminosis D in patients on hemodialysis (HD): related factors and influence on muscle strength

Introducción: La deficiencia de 25 (OH) vitamina D es una alteración prevalente en los pacientes con enfermedad renal crónica (ERC) , sin embargo en nuestro medio no es medida de manera rutinaria y por ende no suele hacerse reposición vitamínica. Nuestro objetivo fue determinar la prevalencia y los factores relacionados a deficiencia de 25 (OH) D en pacientes con ERC en hemodiálisis (HD), particularmente la relación con la función y masa muscular. Métodos: Efectuamos un estudio prospectivo, multicéntrico, en pacientes adultos en HD crónica que no estuvieran recibiendo ningún derivado de la vitamina D. Se midieron en sangre los niveles de 25(OH) D, Hemoglobina, PCR, Albúmina, Ca, P, FAL, PTHi. Se realizó la medición de la fuerza del puño con dinamómetro, y la prueba de sentado-parado. Se aplicó el índice de Karnofsky para clasificar el estado funcional., Se realizó una bioimpedanciometría (BCM; Frese nius Medical Care) en aquellos pacientes sin, contraindicación. Resultados: Se incluyeron 138 pacientes. La 25(OH) vitamina fue de 20.43 ± 10.5 ng/ml, la prevalencia de insuficiencia /defi ciencia 87% (37% con menos de 15 ng/ml). Las concentraciones de vitamina D/deficiencia mostraron correlación/relación significativa con la edad, la presencia de diabetes, los niveles de hemoglobina y albúmina, la fuerza y la masa muscular y la clase funcional (p<0.05) . Conclusión: Alta prevalencia de hipovitaminosis D en pacientes hemodializados particularmente gerontes y diabéticos. Esto estaría relacionado con la desnutrición, anemia, clase funcional y la fuerza/masa muscular de los pacientes, estos últimos dos factores no reportados hasta ahora. Todos estos factores deben ser considerados al momento de la sustitución vitamínica y en la evaluación de la efectividad de la misma.(AU)

Background: 25 (OH) vitamin D deficiency is a prevailing alteration in patients with chronic kidney disease (CKD); however, in our environment, it is not routinely measured and, therefore, vitamin replacement is unusual. Our purpose was assessing the prevalence of and the factors related to 25 (OH) vitamin D deficiency in patientswith CKD in hemodialysis (HD), especially the relation to function and muscle mass. Methods: We conducted a prospective, multicenter study in adult patients on chronic HD who were not receiving any vitamin D derivative. Blood levels of 25 (OH) D, Hemoglobin, CRP, Albumin, Ca,P, ALP and PTHi were measured. The handgrip strength was measured with a dynamometer and the sitting-rising test was carried out. A bioimpedance analysis (BCM; Fresenius Medical Care) was conducted in the patients who had no contraindications. Results: 138 patients were included. The levels of 25 (OH) vitamin D were 20.43±10.5 ng/ml; the insufficiency/deficiency had 87% prevalence (and 37% prevalence with less than 15 ng/ml). Vitamin D concentrations/ deficiency showed a significant correlation with/ relation to age, diabetes, hemoglobin and albumin levels, muscle strength and mass, and functional class (p<0.05). Conclusion: High prevalence of hypovitaminosis D in patients on hemodialysis, particularly in the elderly and in patients with diabetes. This should be related to undernutrition, anemia, the functional class and the muscle strength/mass of patients, the latter two being unreported factors until now. All these factors should be considered when vitamin replacement is conducted and when its effectiveness is assessed.(AU)

[Measuring Kt by ionic dialysance is a useful tool for assessing dialysis dose in critical patients]. / La determinación del Kt por dialisancia iónica es una herramienta útil para la evaluación de la dosis de diálisis en pacientes críticos.

AIM: To evaluate the Kt assessed through ionic dializance (KtOCM) in UCI patients undergoing renal replacement therapy for acute kidney injury, comparing the results with those obtained through the urea removal rate method determined by dialyzate collection (Kturea). MATERIAL AND METHODS: 18 adult UCI staying individuals suffering from renal replacement therapy requiring oliguric acute kidney injury were included in this study. RRT consisted in intermittent or extended hemodialysis performed through a Fresenius 4008E dialysis machine equipped with an on-line clearance monitor (OCM Fresenius). The KtOCM results were provided automatically. The Spearman correlation test was used to assess the relationship between the two exploratory methods and the Student s t test to compare the results obtained by the KtOCM and the Kturea. RESULTS: 35 treatments were analyzed. There were not statistically significant differences between the results form the KtOCM and the Kturea (34.9 +/- 10.69 vs 32.78 +/- 11.31, p = NS). A remarkable association was find between both methods (r = 0.87; 95CI, 0.76-0.94; p < 0.001). CONCLUSIONS: The assessment of Kt through ionic dialyzance is a simple method to estimate the dose of dialysis in critically ill patients and is and useful tool to monitor and adjust the RRT in real time according to a target dose.

La determinación del Kt por dialisancia iónica es una herramienta útil para la evaluación de la dosisde diálisis en pacientes críticos / Measuring Kt by ionic dialysance is a useful tool for assessing dialysis dose in critical patients

Objetivo: Evaluar la determinación de Kt (KtOCM) por dialisancia iónica en los pacientes sometidos a terapia de reemplazo renal (TRR) por insuficiencia renal aguda (IRA) atendidos en una unidad de cuidados intensivos (UCI), comparándola con el Kt obtenido mediante el cálculo del índice de remoción de urea obtenido por recogida del dializado (Kturea). Materiales y métodos: Se incluyeron 18 pacientes adultos, con IRA oligúrica ingresados en la UCI, con requerimiento de TRR, tratados con hemodiálisis intermitente y/o diálisis extendida. Las TRR fueron realizadas con equipos Fresenius 4008E equipados con un monitor de aclaramiento «on-line» (OCM Fresenius). La determinación de KtOCM fue realizada automáticamente por el monitor. Se efectuaron la correlación y la comparación entre KtOCM y Kturea utilizando el análisis de correlación de Spearman y el test de la t, respectivamente. Resultados: Sobre 35 tratamientos efectuados, la media de KtOCM no fue estadísticamente diferente de la del Kturea (34,9 ± 10,69 frente a 32,78 ± 11,31; NS). Se obtuvo una importante correlación y una relación lineal significativa entre los dos métodos (r = 0,87; p <0,001; intervalo de confianza [IC] 95%, 0,76-0,94%). Conclusiones: La determinación del Kt por dialisancia iónica es un método simple para estimar la dosis de diálisis en pacientes críticos y es una herramienta útil para monitorizar y ajustar las TRR en tiempo real de acuerdo con una dosis objetivo (AU)

Aim: To evaluate the Kt assessed through ionic dializance (KtOCM) in UCI patients undergoing renal replacement therapy for acute kidney injury, comparing the results with those obtained through the urea removal rate method determined by dialyzate collection (Kturea). Material and methods: 18 adult UCI staying individuals suffering from renal replacement therapy requiring oliguric acute kidney injury were included in this study. RRT consisted in intermitent or extended hemodialysis performed through a Fresenius 4008E dialysis machine equiped with an on-line clearance monitor (OCM Fresenius). The KtOCM results were provided automatically. The Spearman correlation test was used to assess the relationship between the two exploratory methods and the Student´s t test to compare the results obtained by the KtOCM and the Kturea. Results: 35 treatments were analyzed. There were not statistically significant differences between the results form the KtOCM and the Kturea (34.9 ± 10.69 vs 32.78 ± 11.31, p = NS). A remarkable association was find between both methods (r = 0.87; 95CI, 0.76-0.94; p <0.001). Conclusions: The assessment of Kt through ionic dialyzance is a simple method to estimate the dose of dialysis in critically ill patients and is and useful tool to monitor and adjust the RRT in real time according to a target dose (AU)

Review of pharmacokinetic, pharmacodynamic and clinical studies with a modern combination of amoxicillin/sulbactam.

Amoxicillin/sulbactam is a modern antimicrobial combination. This combination proved to be useful for the treatment of several infections caused by different microorganisms, mainly with the beta-lactamase-producing species. In this review we present the most relevant pharmacokinetic, pharmacodynamic and clinical information associated with its use.

Fast platelet suppression by lysine acetylsalicylate in chronic stable coronary patients. Potential clinical impact over regular aspirin for coronary syndromes.

BACKGROUND: The rapid utilization of fibrinolytics following Q-wave myocardial infarction has clearly modified the evolution of this disease. However, it is still not known whether the immediate inhibition of platelet aggregation (PA) during the coronary event improves outcomes. HYPOTHESIS: The present study was designed to test, in patients with known coronary artery disease (chronic stable angina), whether the particular kinetic pattern of lysine acetylsalicylate (LA) compared with aspirin may affect the time to onset of inhibition of platelet aggregation. METHODS: Ten patients suffering from chronic stable angina participated in this study to compare the efficacy and speed of the inhibition of PA with 320 mg of LA versus 320 mg of aspirin. All patients discontinued the use of aspirin and any other anti-inflammatory agents for 15 days prior to the beginning of the study. They were randomly assigned to LA or aspirin. Blood specimens were obtained to measure the PA at admission, and 5, 10, 20, 30, and 60 min after ingestion. Patients continued to take the assigned drug once a day for the following 4 days. On Day 5, a new blood sample was taken. After this, patients underwent a 15-day wash-out period, and then crossed over to the opposite drug. The samples were analyzed immediately using platelet-rich plasma stimulated with adenosine diphosphate (ADP) 2 mumol/l, collagen 1 microgram/ml, epinephrine 20 mumol/l, and sodium arachidonate acid 0.75 mm/l. RESULTS: The same level of PA inhibition after 30 and 60 min of aspirin administration can be obtained with LA 5 min following ingestion (sodium arachidonate acid: LA: 16.3 +/- 25.9 vs. aspirin 57.6 +/- 8.2; p = 0.00014; collagen: LA 18.9 +/- 20.1 vs. aspirin 47.2 +/- 10.5; p = 0.00092; ADP: LA 27.3 +/- 18.4 vs. aspirin 39.7 +/- 21.8, p = 0.18; epinephrine: LA 22.0 +/- 9.9 vs. aspirin 55.4 +/- 10.9, p = 0.00002. CONCLUSIONS: Platelet aggregation inhibition immediately following LA may have significant clinical implications for the treatment of coronary syndromes.

Intrarenal infusions of endothelin in conscious dogs: interactions with prostanoids and angiotensin II.

Endothelin (2, 5, and 10 pmol/kg/min) was infused into the renal artery of conscious dogs, producing graded and progressive reductions in renal blood flow (RBF) without initial vasodilatation, parallel reductions in glomerular filtration rate (GFR), and reduced Na+ excretion, but little change in urine flow. Pretreatment of the dogs with either ibuprofen (20 mg/kg orally) or aspirin (30 mg/kg p.o.) did not significantly alter the effects of endothelin (5 pmol/kg/min) on RBF, GFR, or Na+ excretion. However, endothelin caused antidiuresis in these cyclooxygenase-inhibited dogs, indicating that the effects of endothelin on water reabsorption were prostanoid mediated. Treatment with captopril (1.5 mg/kg + 0.5 mg/kg/h) did not significantly alter any of the responses to endothelin. The local effects of endothelin in the kidneys of conscious dogs were vasoconstriction and reduced Na+ excretion which were not mediated or modified by either angiotensin II or prostanoids.

[Pruritus in chronic kidney insufficiency]. / Prurito en la insuficiencia renal crónica.

Itching is the dermatologic symptom more often found in patients with chronic renal failure. We have studied 80 patients with end-stage renal disease; itching was present in 56.3% of the cases. We didn't detected in this study any correlation between itching, long term hemodialysis, high calcium, phosphorus, alkaline phosphatase or phosphocalcic product levels. We have seen: 1. Those patients with itching were older than the rest. 2. Itching was important in those patients with residual diuresis less than 500 ml/day (p greater than 0.01). 3. Those men without itching had higher hematocrit levels (p greater than 0.01). 4. Histologic findings on optic and electronic microscopy were more frequent in patients who presented this symptom.