Age may explain the association of an early dialysis initiation with poor survival.

BACKGROUND: Some studies postulate that early dialysis initiation may increase mortality. AIM: The aim of the present study was to assess to what extent this was due to confounding by age. DESIGN: Observational retrospective cohort study. METHODS: We studied all patients starting dialysis therapy between 1 January 1995 and 31 December 2009 in our center. The following variables at dialysis initiation in end-stage renal disease (ESRD) patients were analysed: estimated glomerular filtration rate (eGFR), age, gender, diabetes mellitus, serum albumin, hemoglobin, period of dialysis initiation, history of ischemic heart disease and stroke. Multivariate Cox model was used to calculate adjusted patient survival. RESULTS: Over the last 15 years, 428 patients initiated dialysis therapy in our reference area. Median eGFR at dialysis initiation was 8.16 ml/min. In the univariate analysis, increased eGFR, age, dialysis initiation 1995-1999/2000-2004, diabetes and history of ischemic heart disease were associated (P < 0.05) with increased mortality in ESRD. Patients that started dialysis program with eGFR > 8.16 were older than those who did it with eGFR < 8.16 (66 vs. 61 years, P < 0.001). The association between mortality and eGFR in the crude multivarite Cox model was lost when the model was adjusted by age. In the multivariate Cox model, dialysis initiation period, serum albumin and history of ischemic heart disease were associated with mortality. CONCLUSION: History of ischemic heart disease, serum albumin and dialysis start before 2005 were risk factors for mortality in ESRD patients. Older age is usually associated with early dialysis initiation, so age adjustment is needed to perform studies aimed to calculate the effect of eGFR at dialysis initiation on survival.

Correlación entre el cociente proteína/creatinina en orina esporádica y las proteínas en orina de 24 horas / Correlation between the protein/creatinine ratio in spot urine and 24-hour urine protein

Introducción: Las proteínas presentan una eliminación variable a lo largo del día; por ello clásicamente se ha considerado la proteinuria de 24 horas como el método de referencia para su cuantificación. Dada la dificultad de la recogida de la muestra, aparece el cociente proteína/creatinina (P/C) en orina esporádica como herramienta diagnóstica. Objetivo: El objetivo de este estudio es evaluar la correlación entre la medida de proteinuria de 24 horas y el P/C, comparando muestras recogidas de forma consecutiva en pacientes del Hospital del Mar durante el último año. Métodos: Estudio observacional transversal en una muestra de 159 determinaciones analíticas del Servicio de Nefrología. Valoración de la correlación entre proteinuria de 24 horas y P/C según diferentes grados de proteinuria mediante el coeficiente de correlación intraclases (CCI) y el coeficiente de correlación de Spearman (CCS). Resultados: Se observó una correlación directa y estadísticamente significativa entre proteinuria/24 horas y P/C en todo el grupo estudiado (CCS: r = 0,91, p < 0,001). Las correlaciones según diferentes grados de proteinuria/24 horas fueron: < 300 mg (CCS: r = 0,498, p < 0,001; CCI: 0,46), 300-3499 mg (CCS: r = 0,828, p < 0,001; CCI: 0,66) y ≥ 3500 mg (CCS: r = 0,181, p = NS; CCI: 0,18). Conclusión: El cociente P/C presenta una buena correlación con valores de proteinuria/24 horas entre 300-3499 mg. Dicha correlación se mantiene, pero con menor intensidad, en < 300 mg. En el grupo estudiado, el cociente P/C en orina esporádica no se correlaciona con la proteinuria/24 horas en rango nefrótico (AU)

Introduction: Measurement of the protein content in a 24-hour urine sample is the definitive method of establishing the presence of abnormal proteinuria. However, the urine collection is cumbersome. The spot urine protein to creatinine ratio seems to be a reliable diagnostic tool for urine protein measurement. Objective: Our aim was to evaluate the spot urine protein/creatinine ratio against 24-h urine total protein excretion in different proteinuria ranges by comparing samples collected simultaneously in patients of Hospital del Mar during the last year. Material and method: Observational, cross-sectional study of 159 consecutive paired determinations of 24-h urine total protein excretion and the spot urine protein/creatinine ratio (P/C) in renal patients. The strength of the correlation was determined by calculating the intraclass correlation coefficient (ICC) and the Spearman correlation coefficient (SCC). Results: Among all groups, there was a significant correlation between 24-hour proteinuria and the P/C ratio (SCC: r=0.91, P<0.001). The correlation in different levels of proteinuria were: <300mg (SCC: r=0.498, P<0.001; ICC: 0.46), 300-3499mg (SCC: r=0.828, P<0.001; ICC: 0.66) and ≥3500mg (SCC: r=0.181, P=NS; ICC: 0.18). Conclusions: In summary, a strong correlation was observed between spot urine protein/creatinine ratio and 24-h urine total protein excretion in proteinuria levels from 300mg/day to 3499mg/day. A lower correlation was also maintained in 24-h urine total protein <300mg. In our experience, there is no relevant correlation between spot urine protein/creatinine ratio and 24-h urine total protein excretion in nephrotic-range proteinuria (AU)

Correlation between the protein/creatinine ratio in spot urine and 24-hour urine protein.

INTRODUCTION: Measurement of the protein content in a 24-hour urine sample is the definitive method of establishing the presence of abnormal proteinuria. However, the urine collection is cumbersome. The spot urine protein to creatinine ratio seems to be a reliable diagnostic tool for urine protein measurement. OBJECTIVE: Our aim was to evaluate the spot urine protein/creatinine ratio against 24-h urine total protein excretion in different proteinuria ranges by comparing samples collected simultaneously in patients of Hospital del Mar during the last year. MATERIAL AND METHOD: Observational, cross-sectional study of 159 consecutive paired determinations of 24-h urine total protein excretion and the spot urine protein/creatinine ratio (P/C) in renal patients. The strength of the correlation was determined by calculating the intraclass correlation coefficient (ICC) and the Spearman correlation coefficient (SCC). RESULTS: Among all groups, there was a significant correlation between 24-hour proteinuria and the P/C ratio (SCC: r=0.91, P<0.001). The correlation in different levels of proteinuria were: <300 mg (SCC: r=0.498, P<0.001; ICC: 0.46), 300-3,499 mg (SCC: r=0.828, P<0.001; ICC: 0.66) and ≥3,500 mg (SCC: r=0.181, P=NS; ICC: 0.18). CONCLUSIONS: In summary, a strong correlation was observed between spot urine protein/creatinine ratio and 24-h urine total protein excretion in proteinuria levels from 300 mg/day to 3,499 mg/day. A lower correlation was also maintained in 24-h urine total protein <300 mg. In our experience, there is no relevant correlation between spot urine protein/creatinine ratio and 24-h urine total protein excretion in nephrotic-range proteinuria.

Stroke in renal transplant recipients: epidemiology, predictive risk factors and outcome.

BACKGROUND: Cerebrovascular and cardiovascular diseases are the most important causes of increased morbidity and mortality in patients with end-stage renal disease. Stroke has been widely reported in chronic dialysis patients, but there is scarce information about stroke in renal transplant recipients (RTR), although cerebrovascular events are the most common and potentially life-threatening neurological complications in them. Our aim is to analyze the prevalence, risk factors, etiopathogenia, clinical aspects and outcome of stroke in RTR. METHODS: We analyzed 403 patients who received one or more renal grafts between 1979 and 2000: group A = patients who had stroke (n = 19); group B = those who did not (n = 384). Medical records and pertinent data were compiled. The risk of stroke was studied using univariate and multivariate Cox regression models. RESULTS: prevalence of stroke in RTR was 7.97% at 10 yr. Time elapsed between renal transplantation (RT) and stroke: 49.3 months. Possible risk factors based on the univariate analyses were: diabetic nephropathy (DN) (p < 0.001) and autosomal-dominant-polycystic-kidney-disease (p = 0.049) as original nephropathies, peripheral vascular disease (PVD) (p < 0.001), diabetes mellitus prior to RT (p = 0.005), age older than 40 yr (p = 0.037) and hypertension (p = 0.049). Other analysed risk factors such as gender, renal function, cytomegalovirus infection, hyperlipidemia, hyperuricemia, erythrocytosis or hypertensive donor failed to show any significant predictive value for stroke in these patients. When multivariate analyses were carried out, we found that DN (OR = 4.8; p = 0.010), PVD (OR = 8.2; p < 0.001) and age > 40 yr (OR = 3.3; p = 0.019) were predictive risk factors for stroke. For group A, hypertension was present in all patients, 68.4% had hyperlipidemia and 42.1% reported previous stroke. Cerebral hemorrhage occurred in seven of 19 (36.84%) of the stroke patients, but no subarachnoid hemorrhage occurred in them. Seven of 12 ischemic strokes were atherotrombotic. Considering all strokes, basal ganglia was the predominant localization. The outcome was poor, as nearly half of the patients died in the 3 months following stroke. CONCLUSIONS: Prevalence of stroke in our RTR population was 7.97%. Cerebral hemorrhage appears to be more prevalent in RTR than in general population. More than that, the cerebral hemorrhage rate we found is higher than that reported elsewhere in RTR. The main predictors of stroke were DN, PVD and age. No patient with interstitial nephropathy suffered stroke. Mortality is high in RTR with stroke.

Effect of steroids and the estrous cycle on uterine neuromedin U receptor expression.

We investigated the role of estrogen and progesterone on rat uterine NmU receptor expression in both intact and ovariectomized animals and examined receptor expression through the estrous cycle. Chronic administration of beta-estradiol 3-benzoate (E2) or progesterone in intact animals was devoid of any effect. RU486 caused a 2-fold up-regulation in NmU receptor density. Ovariectomy caused a 60% decrease in receptor density, but chronic E2 administration to ovariectomized rats significantly increased NmU receptor density. The estrous cycle had no significant effect on NmU receptor density. These results suggest that NmU receptor expression is estrogen-dependent, whereas progesterone or a progestin-induced factor is involved in the modulation of this expression.

Characterization of the rat uterine neuromedin U receptor.

Neuromedin U (NmU) is a novel peptide that potently contracts smooth muscle, including rat uterus in vitro. No receptors have so far been demonstrated in any tissue. We have characterized the receptor for NmU in rat uterine membrane preparations. The binding of [125I] rat NmU was saturable, specific, reversible, and time, temperature, and pH dependent. The nonhydrolysable analog of GTP, GTP-gamma-S, reduced binding in a dose-dependent manner, suggesting that the binding site is coupled to a G-protein. Scatchard analysis of saturation binding studies showed a single class of binding site with a maximal binding capacity of 580 +/- 140 fmol/mg membrane protein and a dissociation constant of 0.35 +/- 0.09 nM (n = 3). Rat NmU and NmU-8 (the C-terminal region of the larger molecule) displaced [125I]rat NmU, displaying an IC50 of 1 x 10(-9) M and 6 x 10(-8) M, respectively. Chemical cross-linking studies demonstrated NmU binding sites on the rat uterus to have an M(r) of 48,500. This band was absent in the presence of 0.2 microM NmU. Thus the rat uterus contains specific NmU binding sites through their physiological role awaits identification.

Effects of peptide YY on the human cardiovascular system: reversal of responses to vasoactive intestinal peptide.

Peptide YY (PYY) reverses the increased intestinal secretion stimulated by vasoactive intestinal peptide (VIP) in humans. VIP also dilates blood vessels, so we investigated the effect of PYY on the cardiovascular system. Six volunteers received PYY, 0.4 and 1.2 pmol.kg-1 x min-1 i.v. for 2 h, reproducing plasma levels seen postprandially and during a diarrheal illness, respectively. Cardiac function was assessed by echocardiography. PYY infused at 0.4 pmol.kg-1 x min-1 had no effect on cardiovascular parameters. PYY infused at 1.2 pmol.kg-1 x min-1 caused a fall in both stroke volume from 128 +/- 8 to 110 +/- 8 ml/beat (mean +/- 95 confidence interval, P < 0.01) and cardiac output from 7.2 +/- 0.4 to 6.1 +/- 0.4 l/min (P < 0.01). Effects of infusion of PYY into the brachial artery at doses of 0-16 pmol/min were assessed using venous occlusion plethysmography in six subjects. PYY infusion caused a dose-dependent fall in forearm blood flow. Six subjects received VIP, 5 pmol.kg-1 x min-1 i.v., causing a rise in heart rate from 55 +/- 3 to 70 +/- 3 beats/min and increased cardiac output from 7.3 +/- 1.1 to 13.1 +/- 1.1 l/min. The addition of PYY, 0.4 pmol.kg-1 x min-1 i.v., did not affect the heart rate significantly but decreased the cardiac output to 10.4 +/- 1.1 l/min (P < 0.01). Infusions of PYY into the brachial artery at 5 pmol/min decreased local vasodilation induced by VIP infused at 2 pmol/min at the same site by 40% (P < 0.01), even though this dose of PYY had no significant effect on local blood flow when given alone.(ABSTRACT TRUNCATED AT 250 WORDS)

The purification and sequence analysis of an avian neuromedin U.

In this study we have purified an avian homologue of neuromedin U from the chicken. Each step of the purification process was followed by a specific radioimmunoassay developed using porcine neuromedin U. Microsequence analysis characterised the peptide to be 25 amino acid residues long with the following sequence: Y-K-V-D-E-D-L-Q-G-A-G-G-I-Q-S-R-G-Y-F-F-F-R-P-R-N. Chicken neuromedin U has marked sequence similarity with the porcine peptide at its bioactive C-terminal region. Our findings demonstrate that the amino acid sequence of neuromedin U is markedly conserved in species which have diverged millions of years ago in evolutionary terms.

Action of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide on the rat vascular system: effects on blood pressure and receptor binding.

The N-terminal fragment (PACAP 27) of the novel neuropeptide, pituitary adenylate cyclase-activating polypeptide 38 (PACAP 38), has 68% homology with vasoactive intestinal polypeptide (VIP). The administration of bolus doses of PACAP 38 and its 27 amino acid N-terminal fragment (PACAP 27) caused a rapid but transient dose-dependent hypotensive effect in the anaesthetized rat. The amplitude and duration of the response obtained by PACAP 38 was comparable with VIP whereas PACAP 27 was three times less potent than VIP. Furthermore, radioreceptor binding studies demonstrated that 125I-labelled PACAP 27 and 125I-labelled VIP bound to membranes prepared from blood vessels. Both PACAP 27 and VIP were capable of displacing the other from these binding sites. We propose that the hypotensive effect is via the same receptor type.

The motor effect of neuromedin U on rat stomach in vitro.

A series of neuromedin U (NmU)-like peptides were found to evoke concentration-response contraction of rat fundic circular muscle in vitro. Isometric contraction of this tissue was induced by rat NmU, porcine NmU-8 and NmU-25, and frog NmU. Rat NmU was significantly more potent than frog NmU. The contractile action of rat NmU upon rat fundic strips was not affected by either atropine or tetrodotoxin indicating a direct effect. Maximal NmU-induced contractions were 10% of the maximal contraction induced by carbachol and ranged between those of the bradykinin and angiotensin II. None of the NmU peptides were active on the circular smooth muscle of the frog stomach or on the small and large intestinal longitudinal smooth muscle of either rat or frog. The results of this study demonstrate that members of the NmU peptide family all induce in vitro contraction of rat gastric circular smooth muscle independent of cholinergic or other neuronal mechanisms. Their activity, however, appears to be both tissue and species specific.

Melanomas de infrecuente localizacion. / Melanoma with an unusual localization

Se presentan y comentan dos casos de melanoma de localizacion infrecuente. El primero de ellos corresponde a un hombre de 69 anos que consulto por epistaxis, diagnosticandose Melanoma Maligno de mucosa nasal. Fue tratado quirurgicamente sin presentar recidiva al ano de evolucion. El segundo caso se trata de una mujer de 64 anos que consulto por dolor y prurito vulvar y en quien se confirmo Melanoma Maligno. Tenia adenopatias regionales y comenzo tratamiento quimioterapico. Se describen las distintas formas clinicas e histologicas de melanoma y tambien se consignan datos estadisticos sobre la frecuencia de las distintas localizaciones

Melanomas de infrecuente localizacion. / Melanoma with an unusual localization

Se presentan y comentan dos casos de melanoma de localizacion infrecuente. El primero de ellos corresponde a un hombre de 69 anos que consulto por epistaxis, diagnosticandose Melanoma Maligno de mucosa nasal. Fue tratado quirurgicamente sin presentar recidiva al ano de evolucion. El segundo caso se trata de una mujer de 64 anos que consulto por dolor y prurito vulvar y en quien se confirmo Melanoma Maligno. Tenia adenopatias regionales y comenzo tratamiento quimioterapico. Se describen las distintas formas clinicas e histologicas de melanoma y tambien se consignan datos estadisticos sobre la frecuencia de las distintas localizaciones

Sequential intraperitoneal administration of nitroprusside in patients maintained on peritoneal dialysis.

Clinical studies were made in order to determine the effects of intraperitoneal nitroprusside on the peritoneal clearances according to different frequencies of drug administration. An important increase of urea and creatinine clearances with 3.75 mg of nitroprusside per liter of dialysis solution was observed. The maximum effects were observed after four consecutive exchanges with the drug; its effects were maintained all through the peritoneal dialysis session and in some cases increased when alternative series of four exchanges with and without drug were carried on. The significative higher increase of the big solutes clearances suggests a vasodilator action of nitroprusside which should be also reflected on an increase of the middle size molecules clearances. Clinical tolerance was excellent and the blood pressure variations were negligible.