Araceli Gallego

Prognosis of Acute Tubular Necrosis: An Extended Prospectively Contrasted Study

The ability to predict the outcome in acute tubular necrosis (ATN) remains elusive despite considerable efforts. Accurate prediction is a crucial priority and has large economical and ethical implications, mainly to judge when treatment is futile and further efforts only prolong miserable agony. To analyze the influence of risk factors in the prognosis of ATN, we applied, in an initial phase, a prospective protocol of demographic data, cause of renal failure, diuresis, need of dialysis and clinical conditions in 228 patients using multiple linear and logistic regression models. In a control phase with 100 consecutive patients, we checked the accuracy of the results previously obtained, evaluating further the overall population of 328 patients in a synthetic phase. Finally, the validation of the equations obtained was verified in 25 patients from another hospital. As a complement of this 4-phase study, detailed statistical comparisons between both linear and logistic multiple regression models were undertaken. Correlation between probability of death obtained with equations from the initial phase applied to control patients and real evolution of these patients, survival or death, was excellent. The study of the synthetic phase revealed coma, assisted respiration, hypotension, oliguria and jaundice as having an independent positive influence on mortality and nephrotoxic etiology and normal consciousness on good prognosis. For the linear model, the same cut-off point of discriminant score (0.9) above which there were no chances for survival could be established in the 4 phases. With the logistic model, it only was found at later phases. The multiple linear was better than the logistic regression model in terms of better correlation with real mortality, better sensitivity and specificity intervals, easier use of discriminant cut-off point and better adjustment of distribution of standardized residuals to expected normal function. Early prognosis of ATN is possible and can be given using simple clinical features. A discriminant score allows to distinguish patients without chances for survival. The multiple linear is better than the logistic regression model in the prediction of the outcome in ATN.

Easy and Early Prognosis in Acute Tubular Necrosis: A Forward Analysis of 228 Cases

Multiple factors still influence the high rate of mortality in acute tubular necrosis. Trying to analyze the influence of each risk factor present in an individual patient and the possible interdependence between these factors, as well as to obtain an early prognosis, we have applied a forward analysis to demographic data, acute renal failure origin, need of dialysis, diuresis and clinical conditions in 228 patients, using a multiple linear regression model contained in a computer package. Based on this approach we have found that three variables: deep neurological coma, persistent blood hypotension and assisted respiration have significant influence on mortality. Also, a regression equation was obtained which could be applied as a discriminant score to patient prognosis. This score, calculated with the three aforementioned variables and oliguria when the nephrologist sees the patient for the first time, allows an easy and early prognosis in each patient with acute tubular necrosis.

Prognosis of Children with Acute Renal Failure: A Study of 138 Cases

Acute renal failure (ARF) in children has a poor prognosis in spite of modern therapeutic techniques. For this reason, it would be useful to have prognostic indicators early in the course of the disease, in order to identify those patients that could benefit most from aggressive treatment. In an attempt to establish valid prognostic factors, we prospectively studied 138 cases of ARF in children. We examined age, sex, etiology of ARF, previous surgery, prerenal origin, clinical situation of the patient when first seen by the nephrologist and complications. All these variables were statistically analyzed individually by univariate tests and, except for sex and complications, also by multiple regression analysis. Median age of the patients was 26 months. The etiology of ARF was nephropathy in 16, tumor in 14, cardiopathy in 85 and other causes in 23 cases. For analysis, patients were divided into patients with and without prerenal ARF. In the prerenal group, mortality-related factors were hypotension, need for ventilatory support, age less than 1 month and serum values of creatinine. In the nonprerenal ARF group, the need for assisted ventilation and the need for dialysis correlate positively with the mortality, while an exclusive nephrological etiology was associated with less probability of death.

Effects of adolescent nicotine and SR 147778 (Surinabant) administration on food intake, somatic growth and metabolic parameters in rats

Tobacco smoking and obesity are worldwide important health problems with a growing impact in adolescent and young adults. One of the consequences of nicotine withdrawal is an increase in body weight that can act as a risk factor to relapse. Experimental therapies with a cannabinoid receptor antagonist have been recently proposed for both cigarette smoking and complicated overweight. In the present study, we aimed to investigate metabolic and hormonal effects of chronic nicotine treatment (during treatment and in abstinence) in an animal model of adolescence as well as to address the pharmacological effects of the novel selective CB1 cannabinoid receptor antagonist, SR 147778 (Surinabant). Adolescence (postnatal days 37-44) and/or post-adolescence (postnatal days 45-59) administration of Surinabant reduced body weight gain, as well as plasma glucose levels and triglycerides. The drug also reduced insulin and leptin secretion, and increased adiponectin and corticosterone levels. The effects showed sexual dimorphisms and, in general, were more pronounced in females. Chronic exposure to nicotine (0.8 mg/kg), from postnatal days 30-44 did not result in overt effects on food intake or body weight gain. However, it altered certain responses to the administration of Surinabant, both when the two drugs were given simultaneously and when Surinabant was administered during the post-adolescence period, along nicotine withdrawal. The present results indicate that the endogenous cannabinoid system is active as a metabolic modulator during adolescence and that nicotine exposure can induce long-lasting effects on metabolic regulation, altering cannabinoid modulation of energy expenditure and metabolism.

Influence of Hypertension on Early Renal Insufficiency in Autosomal Dominant Polycystic Kidney Disease

To determine the potential effect of hypertension on early renal function deterioration, 30 patients (13 normotensive and 17 hypertensive) with autosomal dominant polycystic kidney disease and initially normal renal function were retrospectively analyzed. The decline in renal function was estimated by the slope of the linear regression of creatinine clearance versus time. Analysis was made in terms of standardized slope (slope divided by its standard deviation, i.e., measured in standard deviation units). In the hypertensive group the mean standardized slope was significantly higher than in the normotensive group (-10.89 and -4.98, respectively; p < 0.001). The average mean arterial pressure was significantly lower in the normotensive group with respect to the hypertensive one (95 and 109 mm Hg, respectively; p < 0.0001). There was a significant negative linear relationship between the average values of systolic, diastolic, and mean arterial pressures and standardized slopes. The best prediction equation for renal function deterioration was obtained using a multiple linear regression model in which independent variables were maximum and average diastolic pressures. Therefore, prior to renal insufficiency, a high arterial pressure had a significant contribution to renal function deterioration.

Shape of the Relationship between Hypertension and the Rate of Progression of Renal Failure in Autosomal Dominant Polycystic Kidney Disease

The effect of hypertension on the rate of progression of renal failure was analyzed in 26 patients with autosomal dominant polycystic kidney disease relating the slopes of progression (linear regression of the reciprocal serum creatinine on time) with the average mean arterial pressure, systolic and diastolic pressure, derived over the entire follow-up period for each patient. Hypertension was found in 19 of the 26 patients. Using simple linear regression, there was no significant correlation between the two variables in any case. Using polynomial regression (quadratic and cubic), this relationship fits a sigmoid (for diastolic pressure) or a negative parabolic curve (for mean arterial pressure and systolic pressure); i.e. the lowest and the highest values of mean arterial pressure and systolic pressure were associated with faster rates of progression. Thus, an appropriate model to study this relationship is not the linear but the polynomial regression.

Progression of renal failure in chronic primary glomerular diseases.

The rate of progression of renal failure was analyzed in 19 patients with biopsy-proven chronic primary glomerular diseases, by the slope (regression coefficient) of the linear regression of reciprocal serum creatinine on time. The relative importance of proteinuria, sex, underlying disease and components of arterial pressure (systolic, diastolic and mean) was tested using stepwise multiple linear regression, the dependent variable being the slope of progression. We found that the only variable significantly related with slopes of progression was arterial pressure. Hypertension was found in 14 of the 19 patients. There was a significant linear relationship (p < 0.05) between mean arterial pressure and slopes of progression. Notwithstanding, the best fit to the data follows a quadratic function (p < 0.001 for mean arterial pressure), which corresponds to a negative parabolic curve. Therefore, either low or high values of mean arterial pressure were associated with faster mean progression rates. Thus, an accurate approach of this relationship fits a nonlinear regression model.

Age at Renal Replacement Therapy in Autosomal Dominant Polycystic Kidney Disease

Ana Gonzalo, MD, Servicio de Nefrologia, Hospital Ramon y Cajal, Carretera de Colmenar Km 9,100, E-28034 Madrid (Spain) Dear Sir, In 1989 Gretz et al. [1] pointed out that end-stage renal failure appears earlier in men than in women in autosomal dominant polycystic kidney disease (ADPKD; median age 52 vs. 58 years). Data from the Australia and New Zealand Dialysis and Transplant Registry [2] and recently those from Gabow and Johnson [3] in ADPKDl patients supported Table 1. Age and sex distribution at the start of renal replacement therapy in 82 ADPKD patients

Proteinuria and hypertension in autosomal dominant polycystic kidney disease.

Ana Gonzalo, MD, Servicio de Nefrologia, Hospital Ramon y Cajal, Crta. Colmenar Km 9,100, E-28034 Madrid (Spain) Dear Sir, The prevalence of proteinuria in primary established hypertension was found to be between 10 and 20%. In autosomal dominant polycystic kidney disease (ADPKD) mild to moderate proteinuria has been observed in patients with advanced renal failure [1-3] or more infrequently as a consequence of superimposed glomerular disease. We studied retrospectively 31 young and middle-aged ADPKD patients (13 normo-tensive and 18 hypertensive) with normal renal function. The mean age was 32 years (range from 19 to 45 years). All hypertensive patients underwent treatment with angioten-sin-converting enzyme inhibitors. Before renal function deteriorated, 5 of the 18 treated hypertensive patients developed overt proteinuria (greater than 4 mg/kg/day), whereas it did not appear in the normotensive ones. The average proteinuria was 9.3 mg/kg/day (range from 5 to 12 mg/kg/day). Comparisons between arterial pressure values in the proteinuric and nonproteinuric groups were performed using a nonparametric test (the Wilcoxon two-sample test, i.e. U test), at 1 year and 2 years of follow-up. It was not possible to perform this test for basal data because there was only 1 case with proteinuria. However, this patient exhibited the highest Table 1. Average arterial pressure in proteinuric and nonproteinuric treated hypertensive ADPKD patients during follow-up Basal 1 year 2 years

Evolution de l'effectif génétique de lignées de Drosophila melanogaster soumises à une sélection artificielle

On considère l’évolution de l’effectif génétique de lignées de Drosophila melanogaster soumises à une sélection individuelle pour diminuer le nombre de soies sternopleurales. L’effectif génétique moyen, estimé à partir des généalogies (J AMES , 1962), correspond à celui attendu sous l’effet de la sélection (R OBERTSON , 1961 ; BuRROws, 1984) pendant les 2 premières générations de sélection seulement, période où l’héritabilité est significativement différente de zéro. L’analyse des pourcentages de gènes apportés par chaque famille dans les générations successives (J AMES & McBRIDE, 1958) confirme que les lignées atteignent la fixation du caractère sélectionné dès la 2e génération. On conclut que la variabilité génétique du nombre de soies sternopleurales dans la population initiale est contrôlée par un petit nombre de gènes à effet important et à fréquence intermédiaire (GALLEGO & LÔ PEZ-F ANJ UL, 1983).