Confounding: What it is and how to deal with it

Jager, Kitty J.; Zoccali, Carmine; MacLeod, Alison Murray; Dekker, Friedo W.

doi:10.1038/sj.ki.5002650

Cited by 359 publications

(259 citation statements)

References 10 publications

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“…The independent relationship between eGFR, FGF-23, and ADMA in this cohort was investigated by introducing into the same linear regression model all variables that met criteria to be confounders, 47 46 The relationship between intact FGF-23 and the incidence rate of renal events was investigated by Kaplan-Meier survival analysis and by univariate and multiple Cox regression models. In the survival analysis, patients who died (n=42) were censored at the date of death.…”

Section: Southern Italy Cohortmentioning

confidence: 99%

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Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Tripepi

Kollerits

Leonardis

et al. 2015

Journal of the American Society of Nephrology

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Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are associated with progression of CKD. We tested the hypothesis that ADMA and FGF23 are interactive factors for CKD progression in a cohort of 758 patients with CKD in Southern Europe (mean eGFR6SD, 36613 ml/min per 1.73 m 2 ) and in a central European cohort of 173 patients with CKD (MMKD study, mean eGFR, 64639 ml/min per 1.73 m 2 ). In the first cohort, 214 patients had renal events (decrease in eGFR of .30%, dialysis, or kidney transplantation) during a 3-year follow-up. Both intact FGF-23 and ADMA predicted the incidence rate of renal events in unadjusted and adjusted analyses (P,0.001). There was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P,0.01 in adjusted analyses); the risk associated with raised ADMA levels was highest in patients with low FGF-23 levels. These results were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relationship between plasma ADMA level and renal events (doubling of baseline serum creatinine, dialysis, or kidney transplantation) in the adjusted analyses (P,0.01). Furthermore, in the MMKD cohort there was a parallel, independent competitive interaction between symmetric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001). These findings indicate that the association of ADMA level with the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregulation of the nitric oxide system is involved in CKD progression.

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Section: Southern Italy Cohortmentioning

confidence: 99%

“…In the multiple Cox regression model we included intact FGF-23, ADMA, and eGFR and all variables that met criteria to be confounders. 47 We also tested the full list of variables considered above in a saturated model. The Cox regression model did not violate the proportional hazards assumption.…”

Section: Southern Italy Cohortmentioning

confidence: 99%

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Tripepi

Kollerits

Leonardis

et al. 2015

Journal of the American Society of Nephrology

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“…We adjusted the models for factors fulfilling criteria for confounding, obtaining adjusted eGFRs. 10 Potential confounders were sex, age, country, and working in a for-profit center. A 2-sided P Ͻ 0.05 was considered statistically significant.…”

Section: Data Processing and Analysismentioning

confidence: 99%

Factors Influencing the Decision to Start Renal Replacement Therapy: Results of a Survey Among European Nephrologists

Luijtgaarden

Noordzij

Tomson

et al. 2012

American Journal of Kidney Diseases

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Background:Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT.Study Design: European web-based survey. Predictors: Patient presentations described as uncomplicated patients, patients with unfavorable clinical and unfavorable social conditions, or patients with specific clinical, social, and logistical factors.Setting & Participants: Nephrologists from 11 European countries. Outcomes & Measurements:We studied opinions of European nephrologists about the influence of clinical, social, and logistical factors on decision making regarding when to start RRT, reflecting practices in place in 2009. Questions included target levels of kidney function at the start of RRT and factors accelerating or postponing RRT initiation. Using linear regression, we studied determinants of target estimated glomerular filtration rate (eGFR) at the start of RRT.Results: We received 433 completed surveys. The median target eGFR selected to start RRT in uncomplicated patients was 10.0 (25th-75th percentile, 8.0-10.0) mL/min/1.73 m 2 . Level of excretory kidney function was considered the most important factor in decision making regarding uncomplicated patients (selected by 54% of respondents); in patients with unfavorable clinical versus social conditions, this factor was selected by 24% versus 32%, respectively. Acute clinical factors such as life-threatening hyperkalemia refractory to medical therapy (100%) and uremic pericarditis (98%) elicited a preference for an immediate start, whereas patient preference (69%) and vascular dementia (66%) postponed the start. Higher target eGFRs were reported by respondents from highversus low-RRT-incidence countries (10.4 [95% CI, 9.9-10.9] vs 9.1 mL/min/1.73 m 2 ) and from for-profit versus not-for-profit centers (10.1 [95% CI, 9.5-10.7] vs 9.5 mL/min/1.73 m 2 ).Limitations: We were unable to calculate the exact response rate and examined opinions rather than practice for 433 nephrologists.Conclusions: Only for uncomplicated patients did half the nephrologists consider excretory kidney function as the most important factor. Future studies should assess the weight of each factor affecting decision making. Am J Kidney Dis. 60 (6) P atients with end-stage renal disease (ESRD) receive renal replacement therapy (RRT) to improve their survival and quality of life. The decision of when to start RRT is likely to be guided by the level and rate of decrease in residual kidney function and the clinical condition of the patient. Whereas RRT might be life-saving in certain conditions, dialysis also is unphysiologic and may have life-threatening complications. It carries a significant burden for patients and consumes substantial health care resources. 1 Many studies evaluating associations between the timing of the start of RRT and survival were limited in that they considered only serum creatinine level, which is decreased in pa...

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“…Second, we investigated the predictive power of serum IL-6 in the prospective cohort study. In both logistic and survival analyses, we considered variables that met criteria to be confounders (i.e., variables related [P#0.10] to both the exposure under investigation [serum IL-6 levels below/above the median value] and history of CVD or incident fatal and nonfatal CV events, which are not an effect of the exposure and are not in the causal pathway between the exposure and outcome) (34). Tested covariates included traditional risk factors (age, sex, smoking, diabetes and glucose, cholesterol, and BP), factors specific to CKD (hemoglobin, albumin, eGFR, and urinary protein), antihypertensive treatment, body mass index, and CRP.…”

Section: Statistical Analysesmentioning

confidence: 99%

Association of IL-6 and a Functional Polymorphism in the IL-6 Gene with Cardiovascular Events in Patients with CKD

Spoto

Mattace-Raso

Sijbrands

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature.Design, setting, participants, & measurements In a cohort of 755 patients with stages 2-5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up6SD, 31610 months) and used the functional polymorphism (2174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal.Results In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P,0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the 2174 G/C polymorphism had higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95% CI, 1.15 to 4.00; P=0.02) as well as a 87% higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes. ConclusionsIn patients with stages 2-5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the 2174 G/C polymorphism in the IL-6 gene suggests that IL-6 may be causally involved in the high CV risk in this population.

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Confounding: What it is and how to deal with it

Cited by 359 publications

References 10 publications

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Factors Influencing the Decision to Start Renal Replacement Therapy: Results of a Survey Among European Nephrologists

Association of IL-6 and a Functional Polymorphism in the IL-6 Gene with Cardiovascular Events in Patients with CKD

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