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.

Few studies have assessed the prevalence and outcome of acute renal failure (ARF) in the elderly. Among 437 ARF cases prospectively studied during a nine-year period in a nephrology department, 152 (35%) occurred in patients over 70 years of age (Group 1). Patients over 70 account for only 10.5% of all hospital admissions in our country, and prevalence of ARF was 3.5 times higher in these patients than in younger people. Acute tubular necrosis (ATN) was diagnosed in 40% of Group 1 and 52% of the younger patients (Group 2) (P less than .05), whereas prerenal ARF was found in 47% and 32%, respectively (P less than .001). Dehydration was the most frequent cause of prerenal ARF in the elderly (51%). The etiological distribution of ATN was similar in both groups, being of multifactorial origin in most cases. Oliguria was present in 49% of ATN in Group 1 and in 66% of Group 2 (P less than .05). There were no significant differences in dialysis needs. Mortality was higher in the elderly in all types of ARF, although differences did not reach statistical significance. Need for dialysis, mechanical respiration, decreased level of consciousness, and hypotension were associated with poor prognosis in both groups. Total recovery from ARF in older persons was less frequent and slower than in younger patients. It may be concluded that patients over 70 years of age are at high risk for developing ARF; nevertheless, age should not be used as a discriminating factor in therapeutic decisions concerning ARF.

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.

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Nitric Oxide (NO) is involved in the development and progression of abdominal aortic aneurysms (AAA).We found that inhibition of inducible NO synthase (iNOS) protects mice in an elastase-induced AAA model, significantly inhibiting the production of matrix metalloproteinase-13 (MMP-13). The extracellular MMP inducer (EMMPRIN; CD147) was increased in human AAA biopsies and in wild-type murine AAA but not in AAA from iNOS null mice. In cells overexpressing ectopic EMMPRIN, MMP-13 secretion was stimulated, whereas silencing of EMMPRIN by RNA interference led to significant inhibition of MMP-13 expression. In addition, elastase infusion of MMP-13 null mouse aortas induced a significant increase of EMMPRIN but reduced aortic dilatation when compared with wildtype mice, suggesting that NO-mediated AAA may be mediated through EMMPRIN induction of MMP-13. These findings were further verified in elastase-infused iNOS null mice, in which daily administration of NO caused a significant aortic dilatation and the expression of EMMPRIN and MMP-13. By contrast, in iNOS wild-type mice, pharmacological inhibition of iNOS by administration of 1400 W induced a reduction of aortic diameter and inhibition of MMP-13 and EMMPRIN expression when compared with control mice. Our results suggest that NO may regulate the development of AAA in part by inducing the expression of EMMPRIN and modulating the activity of MMP-13 in murine and human aneurysms. Abdominal aortic aneurysm (AAA) is an age-related multifactorial cardiovascular disease and is usually asymptomatic until rupture or diameter size requires medical intervention. 1,2AAA is characterized by local chronic inflammation, degradation of the medial elastin, and components of the extracellular matrix. Resistance to rupture depends on tensile strength by interstitial collagens, and therefore, collagen-degrading enzymes may play a pivotal effect. 3Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes involved in the development and progression of AAA in humans and mice. The effect of collagenases MMP-8 3 and MMP-13, 4 gelatinases A and B, 5 and membrane type MMPs 6 have been extensively analyzed. In particular, collagenases are responsible of cleavage of type I and III collagens, which are involved in keeping the vessel tensile strength, and therefore, increased production of collagen-degrading enzymes may be determinant for the progression of AAA. However, the molecular mechanisms leading to MMP expression and activation are not fully understood.The expression of MMPs have been recently associated to cardiovascular disease through the activation of the extracellular MMP inducer (EMMPRIN; Basigin and CD147).7 EMMPRIN is an immunoglobulin, which induces the expression of MMP-2, MMP-9, and MT1-MMP. 8 -13 Acute and chronic inflammation induces the expression of EMMPRIN by immune cells and vascular endothelial cells, and its role on MMP expression was related to atherosclerosis. 14,15Here we show the association of EMMPRIN and MMP-13 in human AAA and during the NO-me...