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Graft rejection remains an important cause of renal allograft failure, despite improvements in immunosuppression and HLA typing. Although HLA matching is beneficial, ensuring an exact match it is often impractical. Thus, a reliable in vitro method for quantitating and qualitating alloreactivity is an important goal. In this study, we measured in vitro the cytokine secretion profiles of mononuclear cells from patients prior to renal transplantation by stimulating with anti- CD3 monoclonal antibody and suppressing with cyclosporine. Mononuclear cells from patients who subsequently developed acute cellular rejection secreted higher mean levels of interleukin (IL)-2 and γ-interferon (IFN-γ) than those from patients who had no rejection episodes. IFN-γ secretion was significantly associated with rejection (P=0.002), whereas IL-2 secretion did not quite reach statistical significance. There was no significant correlation between IL-4 levels and rejection. Although cyclosporine suppressed the secretion of both IL-2 and IFN-γ, there was no difference in sensitivity to suppression between rejectors and nonrejectors. These results further emphasize the importance of the TH1 lymphocyte subset in renal allograft rejection. The IFN-γ secretory capacity of alloreactive T cells may influence the outcome of a renal allograft by (1) activating graft infiltrating macrophages and/or (2) up-regulating HLA molecules on the graft.
Objectives: To apply the RIFLE criteria “risk,” “injury,” and “failure” for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. Design: Retrospective analysis of the Riyadh Intensive Care Program database. Setting: Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. Patients: Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. Interventions: None. Measurements and Main Results: Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. Conclusions: The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.
Daily APACHE II assessments to reflect the dynamic pathophysiologic processes affecting ICU patients were carried out prospectively on 212 adult ICU admissions for the purpose of predicting hospital outcome. Trend analysis of daily APACHE II scores was used to develop the first set of criteria for predicting deaths among the ICU patients. The analysis took into account the absolute value of APACHE II score of each day and the rate of change relative to that of the previous day. One hundred consecutive adult ICU admissions were used to determine the criteria that were tested on the following 112 consecutive adult ICU admissions. Daily APACHE II scores identified correctly 16 of the 34 patients who died. A second set of criteria was next derived by raising the values of the original limits in order to build-in greater margins of safety without too great a loss of sensitivity. The predictive power of daily APACHE II scores using the second set of criteria was superior to that of a single APACHE II score by a factor of 4. Predictions were not used to influence clinical decision-making during this study.
To the Editor: In the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study (Oct. 22 issue),1 investigators compared low-intensity versus high-intensity renal-replacement therapy. One of the secondary outcomes was the development of new organ failure. However, the criteria for “nonrenal organ failure” were not provided. Second, in subgroup analyses, the RENAL study showed that there was no mortality benefit with high-intensity treatment in patients with sepsis, cardiovascular dysfunction, or failure of at least one nonrenal organ. In a study involving 1847 critically ill patients receiving renal-replacement therapy, we recently reported that the number of failed organ systems at the time of such therapy had a significant effect on the rate of death in the intensive care unit, ranging from 38% in patients with one organ failure to 85.6% in patients with more than three failed organ systems.2 The RENAL study was not designed to perform subgroup analyses in patients with three or more associated failed organ systems. The question remains whether renal-replacement therapy should be individualized in patients with acute kidney injury and multiorgan failure and whether there is a role for high-intensity renal-replacement therapy in this group.
This study used the Acute Physiological and Chronic Health Evaluation (APACHE II) system to select two groups of ICU patients with comparable risk of hospital death to evaluate the importance of GI dysfunction, defined as failure to tolerate enteral nutrition (EN), as a prognostic factor. In our ICU, patients who have not undergone recent bowel surgery are treated by EN. Those patients who cannot tolerate EN are treated by total parenteral nutrition (TPN). One hundred and eleven patients who tolerated EN (functioning gut) and 97 TPN patients who failed to tolerate EN (GI dysfunction) were studied. The mean APACHE II scores of the two groups were 17.7 ± 6.5 (sd) and 17.7 ± 5.1, respectively. The observed mortality of patients with GI dysfunction (51%) was significantly higher (p < .0005) than that of patients with a functioning gut (25%). This was associated with significantly poorer APACHE II mean BP, oxygenation, and creatinine scores among the GI dysfunction patients. Our results suggest that shock, ischemia, and hypoxemia, in addition to causing impairment of renal function, may bring about changes in the GI tract, evident clinically only as a failure to tolerate EN, which have an adverse effect on the prognosis of ICU patients so affected.
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