1,143 research outputs found

    Defining and Estimating Intervention Effects for Groups that will Develop an Auxiliary Outcome

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    It has recently become popular to define treatment effects for subsets of the target population characterized by variables not observable at the time a treatment decision is made. Characterizing and estimating such treatment effects is tricky; the most popular but naive approach inappropriately adjusts for variables affected by treatment and so is biased. We consider several appropriate ways to formalize the effects: principal stratification, stratification on a single potential auxiliary variable, stratification on an observed auxiliary variable and stratification on expected levels of auxiliary variables. We then outline identifying assumptions for each type of estimand. We evaluate the utility of these estimands and estimation procedures for decision making and understanding causal processes, contrasting them with the concepts of direct and indirect effects. We motivate our development with examples from nephrology and cancer screening, and use simulated data and real data on cancer screening to illustrate the estimation methods.Comment: Published at http://dx.doi.org/10.1214/088342306000000655 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Acute kidney injury in the elderly: predisposition to chronic kidney disease and vice versa.

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    There have been considerable advances in the past few years in our understanding of how chronic kidney disease (CKD) predisposes to acute kidney injury (AKI) and vice versa. This review shows, however, that few studies have focused on the elderly or conducted stratified analysis by age. It does appear that elderly patients with estimated glomerular filtration rate (eGFR) 45-59 ml/min/1.73 m(2) are at higher risk for AKI compared with their counterparts with eGFR >60 ml/min/1.73 m(2). This is a similar relationship to that seen in younger patients, although effect size appears smaller. As the incidence of AKI has been increasing over the past several years, the proportion of elderly patients surviving after AKI has also been increasing. Since AKI heightens the risk for the development and acceleration of CKD, this implies significant public health concerns with regard to the absolute number of elderly persons developing incident CKD

    Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.

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    ObjectiveTo compare different blood pressure (BP) levels in their association with the risk of renal outcomes in type 1 diabetes and to determine whether an intensive glycemic control strategy modifies this association.Research design and methodsWe included 1,441 participants with type 1 diabetes between the ages of 13 and 39 years who had previously been randomized to receive intensive versus conventional glycemic control in the Diabetes Control and Complications Trial (DCCT). The exposures of interest were time-updated systolic BP (SBP) and diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h) or stage III chronic kidney disease (CKD) (sustained estimated glomerular filtration rate <60 mL/min/1.73 m2).ResultsDuring a median follow-up time of 24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria. In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg. DBP in the <70 mmHg range were associated with a 0.73 times higher risk of macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was noted between BP and prior DCCT-assigned glycemic control strategy (all P > 0.05).ConclusionsA lower BP (<120/70 mmHg) was associated with a substantially lower risk of adverse renal outcomes, regardless of the prior assigned glycemic control strategy. Interventional trials may be useful to help determine whether the currently recommended BP target of 140/90 mmHg may be too high for optimal renal protection in type 1 diabetes

    Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study

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    BACKGROUND: Creatinine secretion, as quantified by the ratio of creatinine clearance (CrCl) to glomerular filtration rate (GFR), may introduce another source of error when using serum creatinine concentration to estimate GFR. Few studies have examined determinants of the CrCl/GFR ratio. We sought to study whether higher levels of albuminuria would be associated with higher, and being non-Hispanic black with lower, CrCl/GFR ratio. METHODS: We did a cross-sectional analysis of 1342 patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR) and 24-hour urine collections. Our predictors included urine albumin as determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999 and ≥3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion. RESULTS: Mean iGFR was 48.0 ± 19.9 mL/min/1.73 m(2), median albuminuria was 84 mg per day, and 36.8% of the study participants were non-Hispanic black. Mean CrCl/iGFR ratio was 1.19 ± 0.48. There was no association between the CrCl/iGFR ratio and urine albumin (coefficient 0.11 [95% CI−0.01-0.22] for higest verus lowest levels of albuminuria, p = 0.07). Also, there was no association between race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was−0.03 [95% CI−0.09-0.03] compared with whites, p = 0.38). CONCLUSIONS: Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature

    Plasma levels in sepsis patients of annexin A1, lipoxin A4, macrophage inflammatory protein-3a, and neutrophil gelatinase-associated lipocalin

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    AbstractBackgroundThe relationship between the various cytokine responses that occur during sepsis remains controversial. Emerging evidence indicates that the proinflammatory and anti-inflammatory responses are regulated simultaneously from the beginning of sepsis. However, the roles of the novel anti-inflammatory mediators annexin (Anx)A1 and lipoxin (LX)A4 and the proinflammatory cytokines neutrophil gelatinase-associated lipocalin (NGAL) and macrophage inflammatory protein (MIP)-3a have been studied.MethodsIn this study, the plasma levels of AnxA1, LXA4, NGAL, MIP-3a, interleukin (IL)-8 and IL-6 in patients with sepsis were determined on admission to the intensive care unit. The patients were classified into survivors and non-survivors based on their outcome on day 28.ResultsAnxA1 and LXA4 levels were decreased in sepsis patients compared with control patients, whereas the levels of the proinflammatory cytokines MIP-3a, NGAL, IL-8, and IL-6 were elevated. Furthermore, a significantly higher level of MIP-3a was detected in nonsurviving patients compared with surviving patients (p < 0.05), whereas there were no significant differences between these two groups for the levels of the other mediators. Correlation analysis demonstrated that only NGAL level was closely correlated with the level of IL-6. Univariate analysis indicated that the levels of MIP-3a and IL-8 were independent factors associated with patient survival, but this was not confirmed by the multivariate analysis.ConclusionAnxA1 and LXA4 plasma levels were found to be decreased in sepsis patients, whereas the levels of MIP-3a and NGAL were found to be elevated. This warrants further study in order to determine the clinical implications of these changes
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