Plasma cytokine levels predict mortality in patients with acute renal failure

BACKGROUND: Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness. RESULTS: When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients. CONCLUSION: There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.     

Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis

BACKGROUND: Acute renal failure (ARF) is a life-threatening entity that frequently complicates advanced liver disease. This study documents a number of factors that may predispose to or precipitate ARF and influence outcomes in patients with advanced liver disease. Comparisons are also made between subgroups of patients with viral and alcohol-induced liver cirrhosis in those with ARF. PATIENTS AND METHODS: We conducted a retrospective chart review over one year of 127 consecutive hospital admissions in 82 patients who were diagnosed with advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A diagnosis of ARF was made in 29 admissions and another 98 admissions not complicated by ARF served as controls. This study evaluated different etiologies of ARF and developed a database which included clinical features, biochemical parameters, the etiology of cirrhosis, possible predisposing factors, and precipitating events. Version II of the Acute Physiology and Chronic Health Physiology Scoring system (APACHE II) was applied to predict short-term hospital mortality rates. RESULTS: ARF occurred in 29 admissions over the one-year study period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73% were men. The patients with ARF had significant hyponatremia and higher levels of serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white cell counts on admission than the controls. Patients who developed ARF were more likely to have had infection, especially septicemia, and gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients with viral cirrhosis and ARF were found to have higher leukocyte counts, serum bilirubin levels, and more frequent incidence of infection, septicemia and GI bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those with viral hepatitis were also significantly older and had more frequent incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and less frequent incidence of encephalopathy. CONCLUSIONS: The risk of ARF is significantly increased in patients with advanced liver cirrhosis presenting with marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and GI bleeding. The presence of ARF leads to higher mortality rates in both viral and alcohol-induced liver cirrhosis.     

Role of hypoalbuminemia and hypocholesterolemia as copredictors of mortality in acute renal failure.

Role of hypoalbuminemia and hypocholesterolemia as co-predictors of mortality in acute renal failure. BACKGROUND: Hypoalbuminemia (LA) and hypocholesterolemia (LC) have been reported to portend high mortality in both older patients and in patients with end-stage renal disease. Even though low levels have been reported in critically ill patients, they have not been clearly defined as predictors of mortality in acute renal failure (ARF). The impact of LA and LC on mortality in ARF is evaluated in this study. METHODS: We conducted a computer-assisted three-year retrospective review of all cases of de novo ARF seen at an inner city tertiary-care facility. One hundred cases met the criteria for inclusion in the study. We employed both univariate and multivariate logistic regression models to estimate the relative risks (RR) and 95% confidence intervals (CI) of mortality associated with several variables. RESULTS: Predictors associated with a high risk of death identified in this study include LC < or = 150 mg/dl (< or = 3.9 mmol/liter; RR, 7.4; CI, 2.7 to 20.3), LA < or =35 g/liter (RR, 5.0; CI, 1.9 to 13.2), sepsis (RR, 9.4; CI, 3.7 to 23.9), mechanical ventilation (RR, 10.8; CI, 2.8 to 41.0), oliguria (RR 17.0; CI, 6.2 to 46.6), and multisystem organ failure (RR 24.7; CI, 10.3 to 59.1). The overall gross mortality was 39%, but mortality among intensive care unit patients was 82%. Survival was 82% among patients with serum albumin >35 g/liter versus 48% among those with serum albumin < or =35 g/liter (chi2 = 11.9, P = 0.0006). Similarly, survival was higher among patients with cholesterol >150 mg/dl (>3.9 mmol/liter) than those whose levels were < or =150 mg/dl (< or =3.9 mmol/liter; 85 vs. 44%, ch 17.3, P<0.0001). Significant association between LA and LC was observed (R = 0.4, P<0.0001). Age, gender, level of plasma creatinine, and underlying chronic medical conditions were not predictive of mortality. CONCLUSION: Survival in ARF is significantly altered by the levels of albumin and cholesterol. Because both LC and LA can be cytokine mediated, their presence in ARF should be considered ominous.     

Acute renal failure in neonates: Incidence,etiology and outcome

Acute renal failure (ARF) occurs in as many as 8% of neonates admitted to neonatal intensive care units. Most often, ARF is recognized because of oliguria (urinary flow rate <1 ml/kg per hour) although nonoliguric neonatal ARF is being detected with increasing frequency. Among urinary indices utilized to differentiate oliguric neonatal ARF from prerenal oliguria, a fractional excretion of sodium greater than 3% or a renal failure index (RFI) greater than 3 are helpful in confirming ARF. Such indices must be viewed with caution in very premature infants who may have a physiologically high sodium excretion rate and in neonates with the nonoliguric form of ARF. The mortality of oliguric neonatal renal failure may be as high as 60% in medical ARF and even higher in neonates with congenital heart disease, or with anomalies of the genitourinary system. In contrast, nonoliguric renal failure in neonates has an excellent prognosis. Long-term abnormalities in glomerular filtration rate and in renal tubular function are common in survivors of neonatal ARF.Presented at the annual meeting of the American Society of Pediatric Nephrology, 5 May 1986, organized by Dr. R. N. Fine, Los Angeles.     

影响急性肾功能衰竭患者住院病死率与肾脏预后的危险因素分析

目的：探讨影响急性肾功能衰竭（ARF）住院患者病死率与肾脏预后的危险因素,以提高ARF的治疗水平。方法：通过对我院近10年422例ARF患者临床资料的回顾性研究,应用二值多元Logistic回归和线性回归分析对影响ARF患者病死率与肾脏预后的危险因素进行分析。结果：在32项观察因素中发现低血压、昏迷、消化道出血、呼吸衰竭、肝衰竭、心力衰竭、肿瘤、败血症是患者病死率相关的危险因素;肿瘤、呼吸衰竭、心力衰竭为影响肾功能恢复的危险因素。结论：上述危险因素是影响ARF患者病死率、导致肾功能难以恢复的原因,并与患者的近期预后密切相关。     

Acute renal failure due to HELLP syndrome and acute renal failure in mid gestation

A 34-year-old grand multipara (para 7, 4 alive) was managed at the National Hospital, Abuja, Nigeria for acute renal failure due to HELLP syndrome following referral from a peripheral hospital. She presented with a history of vomiting, headache, epigastric pain, loss of consciousness and tonic/clonic seizures. Though she was unsure of her exact dates, clinically the gestational age was estimated at 22 weeks. She was managed in the intensive care unit, following delivery of a macerated fetus within 15 h of hospital admission. The patient received mechanical ventilation and three sessions of haemodialysis as part of her successful management while in the intensive care unit. The uncommon presentation of eclampsia and HELLP syndrome before obvious preeclampsia is discussed, as well as the other signs and symptoms and patient management. The case also highlights the resource-poor environment of peripheral and tertiary hospitals in Nigeria.     

Declining mortality in patients with acute renal failure, 1988 to 2002

Despite improvements in intensive care and dialysis, some experts have concluded that outcomes associated with acute renal failure (ARF) have not improved significantly over time. ARF was studied in hospitalized patients between 1988 and 2002 using the Nationwide Inpatient Sample, a nationally representative sample of discharges from acute-care, nonfederal hospitals. During a 15-yr period, 5,563,381 discharges with ARF and 598,768 with ARF that required dialysis (ARF-D) were identified. Between 1988 and 2002, the incidence of ARF rose from 61 to 288 per 100,000 population; the incidence of ARF-D increased from 4 to 27 per 100,000 population. Between 1988 and 2002, in-hospital mortality declined steadily in patients with ARF (40.4 to 20.3%; P < 0.001) and in those with ARF-D (41.3 to 28.1%; P < 0.001). Compared with 1988 to 1992, the multivariable-adjusted odds ratio (OR) of death was lower in 1993 to 1997 (ARF: OR 0.62, 95% confidence interval [CI] 0.61 to 0.64; ARF-D: OR 0.63, 95% CI 0.59 to 0.66) and 1998 to 2002 (ARF: OR 0.40, 95% CI 0.39 to 0.41; ARF-D: OR 0.47, 95% CI 0.45 to 0.50). The percentage of patients who had ARF with a Deyo-Charlson comorbidity index of 3 or more increased from 16.4% in 1988 to 26.6% in 2002 (P < 0.001). This study provides evidence from an administrative database that the incidence of ARF and ARF-D is rising. Despite an increase in the degree of comorbidity, in-hospital mortality has declined.     

Race and mortality after acute renal failure

Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference.     

Incidence, risk factors, and prognosis of gastrointestinal hemorrhage complicating acute renal failure

BACKGROUND: Few prospective data are currently available on acute gastrointestinal hemorrhage (AGIH) as a complication of acute renal failure (ARF). The aim of the present study was to define incidence, sources, risk factors, and outcome of AGIH in patients with ARF. METHODS: We performed a prospective study on an inception cohort of 514 patients admitted for ARF to a nephrology intermediate care unit. Data on clinical risk factors for bleeding, frequency of occurrence of AGIH, length of hospital stay, and in-hospital mortality were collected. Independent predictors of AGIH were identified. The relative odds of death and the relative increase in length of hospital stay associated with AGIH were calculated after adjusting for baseline comorbidities. RESULTS: Sixty-nine patients out of 514 [13.4% (95% CI, 10.6 to 16.7)] had AGIH as a complication of ARF; 59 were upper AGIH. Forty patients had clinically important bleeding. Erosions and/or ulcers accounted for 71% of cases of upper AGIH. Independent baseline predictors of AGIH were represented by severity of illness [odds ratio 1.45 (95% CI, 1.05 to 2.01) for every 10 point increase in APACHE II score], low platelet count [<50,000 mm3; 3.71 (1.70 to 8.11)], noncirrhotic chronic hepatic disease [2.22 (1.09 to 4.55)], liver cirrhosis [3.38 (1.50 to 7.60)], de novo ARF [2.77 (1.30 to 5.90)], and severe ARF [2.07 (1.10 to 3.88)]. In-hospital mortality was 63.8% in patients with AGIH and 34.2% in the other patients; after adjusting for baseline confounders, AGIH remained significantly associated with an increase in both mortality [2.57 (1.30 to 5.09), P = 0.006] and length of hospital stay [37% (1 to 87%), P = 0.047]. CONCLUSIONS: AGIH and clinically important bleeding are frequent complications of ARF. In this clinical condition, AGIH is more often due to upper gastrointestinal bleeding and is associated with a significantly increased risk of death and length of hospital stay. Both renal and extrarenal risk factors are related to the occurrence of AGIH.     

Prediction of mortality in acute renal failure in the tropics

Despite significant improvements in medical care, acute renal failure (ARF) remains a high risk for mortality. It is important to be able to predict the outcome in these patients in view of the emotional and ethical needs of the patients and to address questions of efficiency and quality of care. We analyzed the risk factors predicting mortality prospectively in a group of 265 patients using univariate and multiple logistic regression analysis. A prognostic model was evolved that included 10 variables. The model showed good discrimination [(receiver operating characteristic (ROC) area=0.91) and correctly classified 88.30% of patients. The variables significantly associated with mortality were coma odds ratio (OR)=9.8], oliguria (OR=4.9), jaundice (OR=3.7), hypotension (OR=3.1), assisted ventilation (OR=2.3), hospital acquired ARF (OR=2.3), sepsis (OR=2.2), and hypoalbuminemia (OR=1.7). Age and male gender were included in the model as they are clinically important. The score was validated in the same sample by boot strapping. It was also validated in a prospective sample of 194 patients. The model was calibrated by the Hosmer-Lemeshow goodness-of-fit test. It was compared with two generic illness scores and one specific ARF score and was found to be superior to them. The model was verified in different subgroups of ARF like hospital acquired, community acquired, intensive care settings, nonintensive care settings, due to sepsis, due to nonsepsis etiologies, and showed good predictability and discrimination.     

Anesthesiologists are living longer: mortality experience 1992 to 2001

STUDY OBJECTIVE: To determine whether there has been any recent change in the mortality experience of American anesthesiologists. DESIGN: Retrospective analysis of obituary reports to the Physician Master File (PMF) of the American Medical Association. MEASUREMENTS: Data were collected from the PMF of anesthesiologists and obstetricians. All data were identified from the PMF. A total of 1525 obituaries of anesthesiologists and 2773 obituaries of obstetricians during the study period, 1992 to 2001, were reviewed. Mean age of living or mean age at death of anesthesiologists and obstetricians, as well as age-adjusted death rates was calculated. MAIN RESULTS: A gradual increase in age at death was noted from 1992 (65.30 +/- 15.61 years) to 2001 (78.13 +/- 12.89 years) for anesthesiologists (P < 0.005). There was a significant linear decrease from 4.3 deaths per thousand to 2.3 deaths per thousand for anesthesiologists in this same period. CONCLUSIONS: We observed a significant increase in the average age at death and a decreased risk of death among anesthesiologists who died in the years 1992 to 2001. Parallel changes were observed in the control population of obstetricians.     

Incidence and etiology of acute renal failure among ambulatory HIV-infected patients

BACKGROUND: Acute renal failure (ARF) is a cause of renal dysfunction in human immunodeficiency virus (HIV)-infected patients. Its incidence and causes have not been studied since the introduction of highly active antiretroviral therapy (HAART) in HIV ambulatory patients. METHODS: This is a prospective cohort study of 754 HIV patients, 18 years or older, seen at a university-based infectious disease clinic between 2000 and 2002. ARF was identified using proportional increases in serum creatinine from baseline and by chart review. Clinical conditions were assessed at the time of the ARF event. ARF incidence rates (IR) were calculated by dividing the number of events by person time at risk. To compare patients with and without ARF, t test or chi-square test were used. RESULTS: Patient's mean age was 40 years; 68% were male and 61% were black. One hundred-eleven ARF events occurred in 71 subjects (IR 5.9 per 100 person-years; 95% CI 4.9, 7.1). ARF was more common in men, in those with CD4 cell count <200 cells/mm(3), and HIV RNA levels >10,000 copies/mL. These patients more often had acquired immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), and have received HAART. ARF was mainly community-acquired, due to prerenal causes or acute tubular necrosis, and associated with opportunistic infections and drugs. Liver disease was a cause of ARF in HCV-infected patients. CONCLUSION: ARF is common in ambulatory HIV patients. Immunosuppression, infection, and HCV are important conditions associated with ARF in the post-HAART era.     

Clinical profile and factors affecting mortality in acute renal failure.

The records of 110 patients with acute renal failure (ARF) admitted to the Department of Medicine of the Philippine General Hospital during a 5-year period (1983-1988) were reviewed. The objectives were to evaluate the clinical profile of ARF patients and to determine what factors influenced mortality. Infection significantly influenced the causation and prognosis of ARF. Fifteen patients died, for an overall mortality rate of 14%. Forty-six clinical variables were analyzed in order to identify factors correlated with mortality. Four variables significantly increased the risk of death from ARF: older age, hyperkalemia, oliguria, and presence of sepsis on admission. These characteristics define a subset of patients for whom more aggressive treatment of ARF is warranted.