SummaryGenetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-a, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-a (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-a/IL-10 combinations, it was observed that low TNF-a plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-a producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-a plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.

BackgroundAcute kidney injury is a common complication of liver transplantation. In this single-centre retrospective observational study, we investigated the impact of acute kidney disease on liver recipient survival.MethodsThe study population consisted of patients who underwent a liver engraftment between January 2002 and November 2006, at a single transplantation centre in São Paulo, Brazil. Acute kidney injury diagnosis and staging were according to the recommendations of the Acute Kidney Injury Network and consisted of scanning the daily serum creatinine levels throughout the hospital stay. Patients requiring renal replacement therapy prior to transplantation, those who developed acute kidney injury before the procedure or those receiving their second liver graft were excluded from the study.ResultsA total of 444 liver transplantations were performed during the study period, and 129 procedures (29%) were excluded. The remaining 315 patients constituted the study population. In 207 procedures, the recipient was male (65%). The mean age of the population was 51 years. Cumulative incidence of acute kidney injury within 48 h, during the first week after transplantation, and throughout the hospital stay was 32, 81 and 93%, respectively. Renal replacement therapy was required within a week after the transplantation in 31 procedures (10%), and another 17 (5%) required replacement therapy after that period. Mean follow-up period was 2.3 years. Time in days from acute kidney injury diagnosis to initiation of replacement therapy or reaching serum creatinine peak was associated with lower overall survival even when adjusted for significant potential confounders (HR 1.03; 95% CI 1.01, 1.05; p=0.002). Overall, patients experiencing acute kidney injury lasting for a week or more before initiation of replacement therapy experienced a threefold increase in risk of death (HR 3.02; 95% CI 2.04, 4.46; p<0.001).ConclusionsAcute kidney injury after liver transplantation is remarkably frequent and has a substantial impact on patient survival. Delaying the initiation of renal replacement therapy in such population may increase mortality by more than 20% per day.

These findings emphasize low eGFR prior to LTx as a predictor for ESRD or death. The consideration for kidney after liver transplant as a treatment modality should be taken into account for those who develop chronic kidney failure after LTx.

Genetic variations in TGF-β and IFN-γ may interfere with proinflammatory cytokine production and, consequently, may be involved with inflammatory diseases, as acute kidney injury (AKI). We considered that genetic polymorphisms of these cytokines may have a crucial role in the outcome of critically ill patients. To investigate whether the genetic polymorphisms of rs1800470 (codon 10 T/C), rs1800471 (codon 25 C/G) from the TGF-β, and rs2430561 (+874 T/A) from IFN-γ may be a risk factor for ICU patients to the development of AKI and/or death. In a prospective nested case-control study, were included 139 ICU patients who developed AKI, 164 ICU patients without AKI, and 244 healthy individuals. We observed a higher frequency to T/A genotype for IFN-γ (intermediate producer phenotype) and higher frequency of TT GG and TC GG genotype (high producer) for TGF-β polymorphism in overall population. However, these polymorphisms have not been shown as a predictor of risk for AKI and death. We found an increased prevalence of high and intermediate producer phenotypes from TGF-β and IFN-γ, respectively, in patients in ICU setting. However, the studied genetic polymorphism of the TGF-β and IFN-γ was not associated as a risk factor for AKI or death in our population.

Objective: To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay. Methods: Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study. Results: Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m 2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease. Conclusion: Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.

Introduction. Cystatin C has been used in the critical care setting to evaluate renal function. Nevertheless, it has also been found to correlate with mortality, but it is not clear whether this association is due to acute kidney injury (AKI) or to other mechanism. Objective. To evaluate whether serum cystatin C at intensive care unit (ICU) entry predicts AKI and mortality in elderly patients. Materials and Methods. It was a prospective study of ICU elderly patients without AKI at admission. We evaluated 400 patients based on normality for serum cystatin C at ICU entry, of whom 234 (58%) were selected and 45 (19%) developed AKI. Results. We observed that higher serum levels of cystatin C did not predict AKI (1.05 ± 0.48 versus 0.94 ± 0.36 mg/L; P = 0.1). However, it was an independent predictor of mortality, H.R. = 6.16 (95% CI 1.46–26.00; P = 0.01), in contrast with AKI, which was not associated with death. In the ROC curves, cystatin C also provided a moderate and significant area (0.67; P = 0.03) compared to AKI (0.47; P = 0.6) to detect death. Conclusion. We demonstrated that higher cystatin C levels are an independent predictor of mortality in ICU elderly patients and may be used as a marker of poor prognosis.

Background Acute kidney injury is a common complication in solid organ transplants, notably liver transplantation. The MELD is a score validated to predict mortality of cirrhotic patients, which is also used for organ allocation, however the influence of this allocation criteria on AKI incidence and mortality after liver transplantation is still uncertain. Methods This is a retrospective single center study of a cohort of patients submitted to liver transplant in a tertiary Brazilian hospital: Jan/2002 to Dec/2013, divided in two groups, before and after MELD implementation (pre-MELD and post MELD). We evaluate the differences in AKI based on KDIGO stages and mortality rates between the two groups. Results Eight hundred seventy-four patients were included, 408 in pre-MELD and 466 in the post MELD era. The proportion of patients that developed AKI was lower in the post MELD era (p 0.04), although renal replacement therapy requirement was more frequent in this group (p < 0.01). Overall mortality rate at 28, 90 and 365 days was respectively 7%, 11% and 15%. The 1-year mortality rate was lower in the post MELD era (20% vs. 11%, p < 0.01). AKI incidence was 50% lower in the post MELD era even when adjusted for clinically relevant covariates (p < 0.01). Conclusion Liver transplants performed in the post MELD era had a lower incidence of AKI, although there were more cases requiring dialysis. 1-year mortality was lower in the post MELD era, suggesting that patient care was improved during this period.

Platelet transfusion is a common practice to prevent spontaneous bleeding or bleeding due to invasive procedures. Transfusion of allogeneic blood components is associated with increased mortality and a worse clinical outcome. The clot strength is assessed by thromboelastometry and determined by the interaction between platelets and fibrinogen. The compensatory effect of high levels of fibrinogen on clot strength in patients with thrombocytopenia has been demonstrated in different clinical settings including sepsis. We report the case of a patient with severe thrombocytopenia whose thromboelastometry showed clot strength that was compensated for by the increase in plasma fibrinogen levels as an acute phase reactant of septic patients. Here, we report a case of a 62-year-old female diagnosed with bone marrow aplasia admitted in the intensive care unit with septic shock and severe thrombocytopenia. During the first 24 hours in the intensive care unit, she presented acute respiratory insufficiency and circulatory shock. The use of invasive mechanical ventilation and norepinephrine was required. Her chest X-ray showed bilateral lung injury. Thus, bronchoscopy with bronchoalveolar lavage was requested. Thromboelastometry was performed and resulted in a normal coagulable profile. Despite severe thrombocytopenia (1,000/mm3), fibrinogen levels were increased (1,050mg/dL) due to septic shock. Bronchoscopy was performed without any active or further bleeding. Here, we report the use of thromboelastometry in the diagnosis of coagulation disorders, preventing unnecessary prophylactic platelet transfusion.