[Study of oxidative stress in advanced kidney disease]. / Estudio del estrés oxidativo en enfermedad renal avanzada.

INTRODUCTION: Introduction Patients with Chronic renal Disease (CRD) often have cardiovascular disease that is the main cause of morbidity and mortality. Oxidative stress and a subclinical inflammation are crucial factors in its development. The aim of this study was to asses the oxidation of the main molecular lines in patients with advanced renal disease without dialysis and to determinate the best biomarker to asses this stress. PATIENTS AND METHODS: We performed an observational study to measure the most important oxidative biomarkers in 32 patients with stage 4 CRD (MDRD = 22.1 +/- 1.08 ml/min) compared with the values obtained in a control group. In peripheral lymphocytes we measured, the lipid peroxidation by Malondialdehyde (MDA) and F2 Isoprostanes in plasma; protein oxidation by glutathione oxidized/reduced ratio (GSSG/GSH) in peripheral lymphocytes and protein carbonyls in plasma and the oxidative damage in genetic material by modified nucleotide base 8-deoxiguanosina oxo -(8-oxo-dG), after isolating nuclear and mitochondrial DNA. We also studied the antioxidant defenses with superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR) and catalase (CAT) in peripheral lymphocytes. We studied the correlation between oxidative stress and the renal function and oxidative stress and co-morbidity factors. RESULTS: All biomarkers showed important differences in comparison with the control subjects. 821.89 +/- 300.47 ng/ml vs. 270 (95.66) * ng/ml (p < 0.000), MDA 0.11 (0.11) * vs. 0.7 +/- 0.31 nmol/mg prot (p <0.000). GSSG / GSH: 6.89 +/- 1.91 vs. 1.39 +/- 0.75 (p <0.000), protein carbonyls: 7.41 +/- 0.84 vs. 3.63 (1.12) *. Nuclear 8-oxo-dG 7.88 (2.32) vs. 2.96 (1.78) * mitochondrial 8-oxo-dG: 15.73 +/- 2.28 vs. 13.85 +/- 1.44 (p <0.05). The Antioxidant enzymes also showed differences. Nuclear 8-oxo-dG demonstrated an important relationship with the rest of biomarkers, homocysteine (r = 0.305, p <0.05), lipoprotein (a) (r = 0.375, p <0.01), mitochondrial 8-oxo-dG (r = 0.411, p <0.05), GSSH/GSH (r = 0.595, p <0.001) and protein carbonyls (r = 0.489, p <0.05). There was an inverse correlation with total protein (r = -0.247, p <0.01), GSH (r = -0.648, p <0.000), GSR (r = -0.563, p <0.001) and SOD (r = -0.497, p <0.000). We did not find any correlation between these parameters and renal function. The presence of diabetes or the treatment with statins did not showed significant differences. * Median (Interquartile range). CONCLUSION: There is an important oxidative stress in patients with advanced renal disease, probably established during early stages of disease. Of the studied parameters, the nuclear 8-oxo-dG is the best marker for oxidative stress in CRD.

[Effect of oxidative stress in patients with chronic renal failure]. / Efecto del tratamiento con hemodiálisis sobre el estrés oxidativo en pacientes con insuficiencia renal crónica.

BACKGROUND: Cardiovascular disease remains the single most common cause of excess morbidity and mortality in end-stage renal disease (ESRD) patients and the traditional risk factors can't explain the high incidence of these events. New "non-traditional" risk factors are analysed in uremic patients and the increased oxidative stress is postulated to be an important contributor to uremic cardiovascular risk. METHODS: In order to evaluate the effects of the hemodialysis treatment, a complete oxidative stress study was performed in fifteen uremic patients. Representative antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stress status in normal control volunteers and in uremic patients treated with hemodialysis (HD). In the latter group blood samples were taken prior and after HD to evaluate the effect of the session of HD over the oxidative markers. RESULTS: Low levels of antioxidant enzyme activities were observed in the uremic patients as compared with normal control subjects. HD treatment results in a significant recovery of these enzyme activities but remain lower as compared with control values. Levels of GSSG and GSH concentrations were increased and reduced respectively in uremic patients. These differences were even higher before the HD and were reduced upon treatment to levels closer to those observed in controls. MDA levels and 8-oxo-dG levels were also increased in uremic patients with the highest values observed in the pre-treated HD group. Even though HD treatment decreases the levels of oxidation products in mononuclear cells of uremic patients the values of the control group are not reached. CONCLUSIONS: Our results suggest that hemodialysis by itself could correct the oxidative status in these patients. The possible mechanisms involved in the oxidative stress changes with the hemodialysis treatment will be discussed below.

Efecto del tratamiento con hemodiálisis sobre el estrés oxidativo en pacientes con insuficiencia renal crónica / Effect of oxidative stress in patients with chronic renal failure

La enfermedad cardiovascular sigue siendo la principal causa de morbi-mortalidadde los pacientes con enfermedad renal crónica en tratamiento dialítico. Losllamados factores de riesgo tradicionales no son capaces de explicar la alta incidenciade estos sucesos por lo que cada vez más se está buscando nuevos factoresde riesgo. Entre ellos el estrés oxidativo aumentado en estos pacientes podríaser un contribuyente importante en el riesgo cardiovascular.Métodos: Para evaluar los efectos del tratamiento con hemodiálisis hemos realizadoun estudio completo del estrés oxidativo en 15 pacientes urémicos. Hemosanalizado enzimas antioxidantes representativas como la superoxidodismutasa, catalasay glutation peroxidasa, junto con el cociente entre glutation oxidado y reducidoy otros indicadores de oxidación como el malonildialdehído y la 8-oxo-2´-deoxiguanosina. El análisis se ha realizado en pacientes hemodializados antes ydespués del tratamiento dialítico y se ha comparado con un grupo control de 16voluntarios sanos.Resultados: Encontramos un aumento de todos los parámetros de oxidación respectoa los del grupo control antes de la hemodiálisis con un descenso significativotras la misma. Los parámetros antioxidantes son significativamente menoresrespecto a los de los controles con mejoría tras la hemodiálisis.Conclusiones: Nuestros resultados sugieren que la hemodiálisis por sí misma podríacorregir el estado pro-oxidante de nuestros pacientes. En el trabajo se analizanlos posibles mecanismos implicados en los cambios en el estrés oxidativo conla hemodiálisis

Background: Cardiovascular disease remains the single most common cause ofexcess morbidity and mortality in end-stage renal disease (ESRD) patients and thetraditional risk factors can’t explain the high incidence of these events. New «non-traditional» risk factors are analysed in uremic patients and the increasedoxidative stress is postulated to be an important contributor to uremic cardiovascularrisk.Methods: In order to evaluate the effects of the hemodialysis treatment, a completeoxidative stress study was performed in fifteen uremic patients. Representativeantioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio(GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA)and 8-oxo-2´-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stressstatus in normal control volunteers and in uremic patients treated with hemodialysis(HD). In the latter group blood samples were taken prior and after HDto evaluate the effect of the session of HD over the oxidative markers.Results: Low levels of antioxidant enzyme activities were observed in the uremicpatients as compared with normal control subjects. HD treatment results ina significant recovery of these enzyme activities but remain lower as comparedwith control values. Levels of GSSG and GSH concentrations were increased andreduced respectively in uremic patients. These differences were even higher beforethe HD and were reduced upon treatment to levels closer to those observedin controls. MDA levels and 8-oxo-dG levels were also increased in uremic patientswith the highest values observed in the pre-treated HD group. EventhoughHD treatment decreases the levels of oxidation products in mononuclear cells ofuremic patients the values of the control group are not reached.Conclusions: Our results suggest that hemodialysis by itself could correct theoxidative status in these patients. The possible mechanisms involved in the oxidativestress changes with the hemodialysis treatment will be discussed below

Efecto del tratamiento con hemodiálisis sobre el estrés oxidativo en pacientes con insuficiencia renal crónica / Effect of hemodialysis therapy on oxidative stress in patients with chronic renal failure

La enfermedad cardiovascular sigue siendo la principal causa de morbi-mortalidadde los pacientes con enfermedad renal crónica en tratamiento dialítico. Losllamados factores de riesgo tradicionales no son capaces de explicar la alta incidenciade estos sucesos por lo que cada vez más se está buscando nuevos factoresde riesgo. Entre ellos el estrés oxidativo aumentado en estos pacientes podríaser un contribuyente importante en el riesgo cardiovascular.Métodos: Para evaluar los efectos del tratamiento con hemodiálisis hemos realizadoun estudio completo del estrés oxidativo en 15 pacientes urémicos. Hemosanalizado enzimas antioxidantes representativas como la superoxidodismutasa, catalasay glutation peroxidasa, junto con el cociente entre glutation oxidado y reducidoy otros indicadores de oxidación como el malonildialdehído y la 8-oxo-2´-deoxiguanosina. El análisis se ha realizado en pacientes hemodializados antes ydespués del tratamiento dialítico y se ha comparado con un grupo control de 16voluntarios sanos.Resultados: Encontramos un aumento de todos los parámetros de oxidación respectoa los del grupo control antes de la hemodiálisis con un descenso significativotras la misma. Los parámetros antioxidantes son significativamente menoresrespecto a los de los controles con mejoría tras la hemodiálisis.Conclusiones: Nuestros resultados sugieren que la hemodiálisis por sí misma podríacorregir el estado pro-oxidante de nuestros pacientes. En el trabajo se analizanlos posibles mecanismos implicados en los cambios en el estrés oxidativo conla hemodiálisis

Background: Cardiovascular disease remains the single most common cause ofexcess morbidity and mortality in end-stage renal disease (ESRD) patients and thetraditional risk factors can’t explain the high incidence of these events New «non-traditional» risk factors are analysed in uremic patients and the increasedoxidative stress is postulated to be an important contributor to uremic cardiovascularrisk.Methods: In order to evaluate the effects of the hemodialysis treatment, a completeoxidative stress study was performed in fifteen uremic patients. Representativeantioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio(GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA)and 8-oxo-2´-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stressstatus in normal control volunteers and in uremic patients treated with hemodialysis(HD). In the latter group blood samples were taken prior and after HDto evaluate the effect of the session of HD over the oxidative markers.Results: Low levels of antioxidant enzyme activities were observed in the uremicpatients as compared with normal control subjects. HD treatment results ina significant recovery of these enzyme activities but remain lower as comparedwith control values. Levels of GSSG and GSH concentrations were increased andreduced respectively in uremic patients. These differences were even higher beforethe HD and were reduced upon treatment to levels closer to those observedin controls. MDA levels and 8-oxo-dG levels were also increased in uremic patientswith the highest values observed in the pre-treated HD group. EventhoughHD treatment decreases the levels of oxidation products in mononuclear cells ofuremic patients the values of the control group are not reached.Conclusions: Our results suggest that hemodialysis by itself could correct theoxidative status in these patients. The possible mechanisms involved in the oxidativestress changes with the hemodialysis treatment will be discussed below

[Hypokalemic metabolic alkalosis: apropos of a case of Gitelman's syndrome]. / Alcalosis metabólica hipopotasémica: a propósito de un síndrome de Gitelman.

We present a case of Gitelman's Syndrome in a 20 year-old woman who came to our service with weakness, asthenia, leg cramps and tetany. Laboratory studies revealed metabolic alkalosis with hypokalemia, hypomagnesemia and low calcium in a 24-hour urine test. The diagnosis of this syndrome is made in some cases during adult life because this syndrome is asymptomatic over several years. Gitelman's Syndrome is autosomal recessive as is Bartter's Syndrome. The gene is located in chromosome 16q, which encodes the cotransporter Na/Cl sensitive to thiazide in the distal convoluted tubule. The defect of cotransporter produces an alteration of sodium reabsorption that causes electrolytic disorders typical of this Syndrome and different from Bartter's Syndrome. The typical electrolytic alterations are hypocalciuria and hypomagnesemia secondary to high urinary magnesium excretion. The prognosis of this syndrome is excellent and treatment consists in correction of serum electrolytes with oral administration of magnesium and potassium. In spite of this treatment, in some cases it is very difficult to reach normal serum levels of magnesium because of the high doses of oral magnesium, which produce common crises of diarrhea that increase magnesium gastrointestinal losses.

Acidosis correction with a new 25 mmol/l bicarbonate/15 mmol/l lactate peritoneal dialysis solution.

OBJECTIVE: The aim of this study was to evaluate the effects of a combined 25 mmol/L bicarbonate/15 mmol/L lactate-based solution (Bic/Lac), compared to a 35 mmol/L lactate solution (Lac)--the most commonly used solution for patients in southern Europe--on the venous plasma bicarbonate level in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This was a randomized, parallel, controlled, open-label study, with patients studied for a period of 3 months preceded by a 1-month baseline and followed by a 1-month follow-up. Patients used the 35 mmol/L lactate solution during baseline and follow-up periods. SETTING: Four Spanish nephrology centers. PATIENTS: Thirty-one (20 Bic/Lac, 11 Lac) well-dialyzed (creatinine clearance > 55 L/week/1.73 m2 body surface area) CAPD patients. INTERVENTIONS: Blood samples were taken for biochemistry tests at all visits. A physical examination was completed at baseline and month 3, and a medical update was completed after 1, 2, and 3 months, and at the follow-up visit. Adverse-event monitoring and notation of prescription changes were carried out continuously. MAIN OUTCOME MEASURE: Effect on venous plasma bicarbonate level. RESULTS: Venous plasma bicarbonate rose by 3.1 mmol/L (confidence intervals 1.6-4.8),from a baseline level of 23.0 mmol/L during the treatment period in those patients treated with Bic/Lac (p < 0.05 vs Lac). The number of acidotic patients (venous plasma bicarbonate < 24 mmol/L) was statistically significantly reduced at every treatment period visit in the Bic/Lac group (p < 0.05). There were no adverse findings with respect to vital signs, physical examination, or clinical symptoms, apart from one death in the control group. CONCLUSIONS: The new Bic/Lac solution allowed better correction of acid-base status than the lactate solution.

[Prevalence of Down's syndrome in Asturias, 1987-1993. Members of the Work Group of the RCDA]. / Prevalencia del síndrome de Down en Asturias, 1987-1993. Miembros del grupo de Trabajo del RDCA.

OBJECTIVE: To determine the frequency of Down Syndrome (DS) in Asturias and the prenatal diagnosis impact on the birth prevalence of this chromosomal anomaly. METHODS: The analysed data came from the Registry of Congenital Defects of Asturias (1990-1993) and from a retrospective study conducted by the same working group (1987-1989). The total prevalence rates and the prevalence at birth were calculated. RESULTS: Out of 55,601 births, DS was recorded in 83 cases: 69 livebirths, two fetal deaths and 12 induced abortions following prenatal diagnosis, giving a total prevalence rate of 14.9 per 10,000 and a birth prevalence of 12.8. The proportion of induced abortions was 15 per cent in this period; the proportion of cases in the high risk maternal age group (35 years and over) was around 50% of the total. The proportion of induced abortions was 15 per cent in this period. CONCLUSIONS: The frequency of DS in Asturias is comparable to the other populations. Prenatal diagnosis had little impact on the birth prevalence figures. These results may help us draw up prevention and prenatal diagnosis policies for these defects in Asturias when giving the frequency of this health problem.

[The quality of the registry of perinatal deaths. Asturias, 1986-90]. / Calidad del registro de muertes perinatales. Asturias, 1986-90.

The quality of official perinatal mortality statistics in a geographical and administratively well defined region (Asturias, Spain) is studied in a five years period (1986-90). The official figures were compared with those collected, retrospectively, from multiple hospital sources. Under-registration of perinatal death was 35% (45.5% of fetal death and 22.5% of early neonatal death, these occurred in the first 24 hours). Validity of mentioned statistics is discussed.