RESUMEN
AIM: The disturbed circadian rhythm in haemodialysis patients results in perturbed sleep. Short term melatonin supplementation has alleviated these sleep problems. Our aim was to investigate the effects of long-term melatonin supplementation on quality of life and sleep. METHODS: In this randomized double-blind placebo-controlled trial haemodialysis patients suffering from subjective sleep problems received melatonin 3 mg day(-1) vs. placebo during 12 months. The primary endpoint quality of life parameter 'vitality' was measured with Medical Outcomes Study Short Form-36. Secondary outcomes were improvement of three sleep parameters measured by actigraphy and nighttime salivary melatonin concentrations. RESULTS: Sixty-seven patients were randomized. Forty-two patients completed the trial. With melatonin, no beneficial effect on vitality was seen. Other quality of life parameters showed both advantageous and disadvantageous effects of melatonin. Considering sleep, at 3 months sleep efficiency and actual sleep time had improved with melatonin compared with placebo on haemodialysis days (difference 7.6%, 95% CI 0.77, 14.4 and 49 min, 95% CI 2.1, 95.9, respectively). At 12 months none of the sleep parameters differed significantly from placebo. Melatonin salivary concentrations at 6 months had significantly increased in the melatonin group compared with the placebo group. CONCLUSIONS: The high drop-out rate limits the strength of our conclusions. However, although a previous study reported beneficial short term effects of melatonin on sleep in haemodialysis patients, in this long-term study the positive effects disappeared during follow up (6-12 months). Also the quality of life parameter, vitality, did not improve. Efforts should be made to elucidate the mechanism responsible for the loss of effect with chronic use.
Asunto(s)
Melatonina/uso terapéutico , Calidad de Vida , Diálisis Renal , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Actigrafía , Anciano , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Suplementos Dietéticos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melatonina/administración & dosificación , Persona de Mediana Edad , Saliva/química , Sueño/efectos de los fármacos , Trastornos del Sueño del Ritmo Circadiano/etiología , Factores de TiempoRESUMEN
AIM: The aim of this study was to investigate the effects of exogenous melatonin on sleep-wake rhythm in haemodialysis patients. METHODS: The study design is a randomized, double-blind, placebo-controlled, cross-over study of 3 x 6 weeks melatonin 3 mg at 22.00 h every night. Haemodialysis patients were asked to fill out a sleep questionnaire and to wear an actometer to record their sleep problems objectively. Furthermore, melatonin concentrations in saliva were sampled the night after daytime haemodialysis and the consecutive night. Actometers, the sleep questionnaire and melatonin concentrations were repeated during the study. RESULTS: In total, 20 patients (six female, median age 71 years) completed the investigation. On nights after daytime dialysis, objective sleep onset latency decreased significantly from a median of 44.5 (placebo) to a median of 15.5 min with melatonin (P < 0.01). Sleep efficiency increased from 67.3 to 73.1% with melatonin (P < 0.05). Actual sleep time increased from 376 min (placebo) to 388 min with melatonin (P < 0.01), and sleep fragmentation decreased from 4.5 to 3.1 (P < 0.01). Furthermore, subjective sleep parameters improved also. Patients reported less time needed to fall asleep (P < 0.05) and fewer wake periods (P < 0.05) on the nights with and without daytime dialysis and an increase in sleep time on the night of daytime dialysis (P < 0.05). Furthermore, the nocturnal melatonin rise was recovered. CONCLUSION: Treatment with melatonin resulted in an improvement of subjective and objective sleep parameters, as well as a recovered nocturnal melatonin rhythm.
Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Melatonina/farmacología , Diálisis Renal , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Sueño/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/tratamiento farmacológico , Masculino , Melatonina/análisis , Melatonina/uso terapéutico , Persona de Mediana Edad , Saliva/química , Encuestas y CuestionariosRESUMEN
Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in Wegener granulomatosis, microscopic polyangiitis and its renal-limited variant (pauci-immune crescentic glomerulonephritis), and Churg-Strauss syndrome. The International Consensus Statement on testing and reporting of ANCA states that ANCA are demonstrated most readily in these conditions by using a combination of indirect immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 or myeloperoxidase. The group that produced the International Consensus Statement has developed guidelines for the corresponding quality control activities, examples of comments for various IIF patterns and ELISA results, and recommendations for ANCA testing when inflammatory bowel disease and other nonvasculitic ANCA-associated autoimmune diseases are suspected.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedades Autoinmunes/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Humanos , Control de CalidadRESUMEN
Molecular biologic techniques are currently considered as new diagnostic and prognostic parameters with a sensitivity and specificity exceeding those of histologic and functional data currently used in clinical practice. The results in various clinical settings have been of limited value up to now. This study is an investigation of the use of tissue levels of RNA determined in routine clinical kidney biopsies as prognostic tools. The focus was on RNA encoding for molecules known to be involved in the pathogenesis of renal disorders. Fresh kidney biopsy tissue was obtained from 52 patients with various renal diseases. The GFR was followed for 12 mo. The extent of glomerulosclerosis and interstitial fibrosis in the biopsies was determined with quantitative digital image analysis. Glomerular and tubulointerstitial compartments from each biopsy specimen were separated, and mRNA levels of TGF-beta, collagen I, collagen IV, and fibronectin were quantitated by real-time PCR. Correlations, along with 95% confidence intervals (CI), between all variables tested at time biopsy were determined. To assess their prognostic value, these variables were correlated with the slope of GFR within several time intervals after biopsy. In addition, to evaluate the predictive value of the variables for outcome in individual patients, differences for each variable were tested between patients showing progressive decline in renal function (slope GFR < 0) and patients showing stable or improving renal function over time (slope GFR >or= 0). In chronic renal diseases, the extent of histologic damage correlated with the GFR at the time of biopsy (r = -0.44; CI -0.68 to -0.11), but it did not correlate with the slope expressing a change in GFR after the biopsy. Tubulointerstitial TGF-beta mRNA levels correlated with the rate of change in GFR between time of biopsy and 1 mo later (r = 0.41; CI, 0.07 to 0.67). The GFR at the time of biopsy correlated with the slope of change in GFR between time of biopsy and 12 mo later (r = -0.50; CI, -0.73 to -0.18). In chronic renal diseases, glomerular fibronectin mRNA levels, in comparison with the GFR at time of biopsy, correlated relatively strongly with the slope of change in GFR between 3 and 12 mo (r = 0.50; CI, 0.16 to 0.74). Patients with favorable renal outcome after 12 mo showed significantly higher TGF-beta mRNA levels and lower proteinuria levels at time of biopsy (P < 0.05) than patients with a progressive decline in renal function. This study shows that mRNA levels measured in kidney biopsies can function as prognostic tools in human renal diseases. In particular, relatively high levels of tubulointerstitial TGF-beta mRNA and glomerular fibronectin mRNA are associated with less deterioration in renal function.