Isac de Castro

Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.

Objectives: Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. Design and Setting: Observational, retrospective study in a 23‐bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. Patients: The inclusion criterion was invasive mechanical ventilation for ≥48 hrs. AKI was defined as at least one measurement of serum creatinine of ≥1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non‐AKI patients (control group). The criterion for weaning was the combination of positive end‐expiratory pressure of ≤8 cm H2O, pressure support of ≤10 cm H2O, and Fio2 of ≤0.4, with spontaneous breathing. The primary end point was duration of weaning and the secondary end points were rate of weaning failure, total length of mechanical ventilation, length of stay in the ICU, and ICU mortality. Results: A total of 140 patients were studied: 93 with AKI and 47 controls. The groups were similar in regard to age, sex, and type of tumor. Diagnosis of acute lung injury/acute respiratory distress syndrome as cause of respiratory failure and Simplified Acute Physiology Score II at admission did not differ between groups. During ICU stay, AKI patients had markers of more severe disease: increased occurrence of severe sepsis or septic shock, higher number of antibiotics, and longer use of vasoactive drugs. The median (interquartile range) duration of mechanical ventilation (10 [6–17] vs. 7 [2–12] days, p = .017) and duration of weaning from mechanical ventilation (41 [16–97] vs. 21 [7–33.5] hrs, p = .018) were longer in AKI patients compared with control patients. Cox regression analysis demonstrated that a ≥85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30–4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24–5.08), and the number of antibiotics (hazard rate, 2.64; 95% confidence interval, 1.51–4.63) predicted longer duration of weaning. The length of ICU stay and ICU mortality rate were significantly greater in the AKI patients. After adjusting for Simplified Acute Physiology Score II, oliguria (odds ratio, 30.8; 95% confidence interval, 7.7–123.0) remained as a strong risk factor for mortality. Conclusion: This study shows that renal dysfunction has serious consequences in the duration of mechanical ventilation, weaning from mechanical ventilation, and mortality in critically ill cancer patients.

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

BACKGROUND Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. STUDY DESIGN Retrospective case series. SETTING & PARTICIPANTS Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the São Paulo University Medical School (São Paulo, Brazil). OUTCOMES & MEASUREMENTS We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. RESULTS 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P < 0.001), lower gestational age (P < 0.001), and birth weight (P < 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P < 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. LIMITATIONS Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. CONCLUSIONS Outcomes of pregnancy in women undergoing hemodialysis often are good. Pre-eclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight.

Mycophenolate Mofetil Attenuates Renal Ischemia/Reperfusion Injury

Immunosuppressive agents may have an impact on ischemia/reperfusion (I/R) injury. The immunosuppressant mycophenolate mofetil (MMF) presents properties that can attenuate such injury. This study investigated the effects of MMF on renal I/R injury. Male Wistar rats received MMF (20 mg/kg per d) or vehicle by gavage beginning 2 d before ischemia and maintained during the entire study. Ischemic injury was induced by bilateral renal arteries occlusion for 60 min. Control rats received MMF and underwent sham operation. At days 1, 2, and 14, post-ischemia renal function was assessed and kidneys were removed for histologic and immunohistochemical studies. MMF given to nonischemic rats did not alter renal function. There was no functional protection at 24 h post-ischemia with MMF. At 2 d, post-ischemia rats pretreated with MMF presented higher inulin clearance compared with untreated rats (0.42 +/- 0.04 versus 0.15 +/- 0.02 ml/min per 100 g; P < 0.001) and attenuated renal blood flow decrease (5.23 +/- 0.28 versus 3.24 +/- 0.37 ml/min; P < 0.01). The immunostaining for intercellular adhesion molecule-1 (ICAM-1) was less intense in rats pretreated with MMF. These rats also presented an earlier decreased infiltrating macrophages/lymphocytes and cell proliferation at day 1 post-ischemia. The functional and immunohistochemical analyses performed at day 14 post-ischemia returned to values similar to controls in both groups of rats. To determine whether mycophenolic acid (MPA) could induce cytoprotection, the effects of MPA on normoxic and hypoxic/reoxygenated (H/R) isolated tubule suspensions were also investigated. MPA was not deleterious to normoxic tubules and it was not protective against H/R tubules. In conclusion, pretreatment with MMF attenuates I/R injury in rats and does not limit the recovery from ischemia. The protective effect of MMF by reducing inflammation precedes the hemodynamic changes and tubular injury.

Mortality Risk Factors and Validation of Severity Scoring Systems in Critically Ill Patients with Acute Renal Failure

Background. Risk stratification and prediction of outcome in acute renal failure patients in the intensive care unit are important determinants for improvement of patient care and design of clinical trials. Methods. In order to identify mortality risks factors and validate general and specific predictive models for acute renal failure (ARF) patients in the intensive care unit (ICU), 324 patients were prospectively evaluated. Multivariate analysis by logistic regression was utilized for identification of mortality risk factors. Discrimination and calibration were used to evaluate the performance of the following models at referral to nephrologist and at initiation of renal replacement therapy: APACHE II, SAPS II, LODS, and ATN-ISI. Organ failure was assessed by SOFA and OSF. Results. The hospital mortality rate was 85%. The identified mortality risk factors were: age ≥ 65 yr, BUN ≥ 70 mg/dL, ARF of septic origin, and previous hypertension. Serum creatinine ≥ 3.5 mg/dL, systolic blood pressure ≥ 100 mm Hg, and normal consciousness were associated with mortality risk reduction. Performance of all prognostic models was disappointing with unsatisfactory calibration and underestimation of mortality on the day of referral to the nephrologist and at initiation of renal replacement therapy. Conclusions. Cross-validation of prognostic models for ARF resulted in poor performance of all studied scores. Therefore, a specific model is still warranted for the design of clinical trials, comparison of studies, and for prediction of outcome in ARF patients, especially in the ICU.

Differences in Sepsis Treatment and Outcomes between Public and Private Hospitals in Brazil: A Multicenter Observational Study

Background Previous studies showed higher sepsis mortality rates in Brazil compared to other developed or developing countries. Moreover, another trial demonstrated an increased mortality rate in public hospitals compared to private hospitals in Brazil. The reasons for these findings may include delayed recognition and inadequate treatment of sepsis in public facilities. We designed this study to evaluate the factors associated with mortality in septic patients admitted to intensive care units in a network of public and private institutions. Materials and Methods This study is a retrospective analysis of a prospective cohort of sepsis patients in 19 private and public institutions in Brazil. We analyzed data from the original database and collected additional data to assess compliance to the treatment guidelines and to determine the time from the onset of organ dysfunction and the sepsis diagnosis by the healthcare team. Results A total of 396 patients were analyzed. Patients in public hospitals were younger, had a greater number of dysfunctional organs at baseline and a lower chance to have sepsis diagnosed within two hours of the onset of organ dysfunction. Private hospitals had a better compliance to lactate and blood culture sampling and maintenance of glycemic control. The multivariate analysis showed that age, disease severity at baseline and being treated at a public hospital were independent risk factors for mortality. A delay in the sepsis diagnosis of longer than two hours was associated with mortality only in the public setting. Conclusions We confirmed a lower sepsis mortality rate in the private hospitals of this network. Being treated in a public hospital was an independent factor for mortality. Delayed recognition of sepsis was more frequent in public institutions and this might have been associated with a higher mortality. Improving sepsis recognition and early diagnosis may be important targets in public institutions.

Performance of the third generation models of severity scoring systems (APACHE IV, SAPS 3 and MPM-III) in acute kidney injury critically ill patients

BACKGROUND Severity scores are useful to guarantee similar disease severity among groups in clinical trials and to enable comparison between different studies. The aim of this study was to assess the performance of the third generation models of severity scoring systems [simplified acute physiology score (SAPS) 3, acute physiology and chronic health evaluation (APACHE) IV and mortality probability model (MPM)-III] in acute kidney injury (AKI) patients in the intensive care unit (ICU). METHODS Three hundred and sixty-six consecutive AKI critically ill patients were prospectively assessed in six ICUs of an academic tertiary care center. Scores were applied on AKI diagnosis day (DD) and on the day of nephrology consultation (NCD). Discrimination was assessed by area under the receiver operating characteristic curve (AUCROC) and calibration by Hosmer-Lemeshow (HL) goodness-of-fit test. RESULTS Hospital mortality rate was 67.8%. SAPS 3 general and Central and South America (CSA) customized equations presented identical good discrimination (AUCROC curve: 0.80 on NCD) and satisfactory HL tests on both analyzed days (P > 0.100). CSA SAPS 3 equation predicted mortality more accurately [standardized mortality ratio (SMR) on NCD = 1.00 (95% confidence interval (CI) 0.84-1.34)]. APACHE IV and MPM-III scores presented similar discrimination compared to SAPS 3 on both analyzed days (P > 0.05). APACHE IV presented satisfactory HL tests over time (P > 0.100) but underestimated mortality [SMR on DD = 1.92 (95% CI 1.61-2.23); SMR on NCD = 1.46 (95% CI 1.48-1.96)]. MPM-III showed unsatisfactory HL test results (P = 0.027 on DD; P = 0.045 on NCD) and underestimated mortality [SMR on NCD = 2.09 (95% CI 1.48-1.96)]. CONCLUSIONS SAPS 3, especially the geographical customized equation, presented good discrimination and calibration performances, accurately predicting mortality in this group of AKI critically ill patients.

Impact of mild acute kidney injury (AKI) on outcome after open repair of aortic aneurysms.

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI (defined as

Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

25% or

Inhalation of fine particulate matter during pregnancy increased IL-4 cytokine levels in the fetal portion of the placenta.

50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied (mean age 68 ± 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were supra-renal aortic cross-clamping (odds ratio 5.51, 95% CI 1.05–36.12, p = 0.04) and duration of operation for AKI 25% (OR 6.67, 95% CI 2.23–19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor (OR 6.13, 95% CI 1.64–22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping (OR 9.6, 95% CI 1.37–67.88, p = 0.02), development of AKI 50% (OR 8.84, 95% CI 1.31–59.39, p = 0.02), baseline GFR lower than 49 mL/min (OR 17.07, 95% CI 2.00–145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period (OR 19.99, 95% CI 2.32–172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Sequential evaluation of prognostic models in the early diagnosis of acute kidney injury in the intensive care unit

Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.