Intercurrent clinical events are predictive of plasma C-reactive protein levels in hemodialysis patients

Tellingen, Anne van; Grooteman, Muriël P.C.; Schoorl, Margreet; Bartels, P. C. M.; Schoorl, Marianne; Ploeg, Tjeerd van der; Wee, Piet M. ter; Nubé, Menso J.

doi:10.1046/j.1523-1755.2002.00470.x

Cited by 58 publications

(50 citation statements)

References 24 publications

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“…Clinical use of the biomarkers to identify patients at risk or who have smoldering infections is not likely valid given that, for example, over one-third of subjects changed from one tertile of CRP to another in the course of just 3 months. This is consistent with the study of van Tellingen et al [17], who found patients frequently changed tertiles of CRP and concluded that clinical judgment was as predictive of infection as was a rise in CRP levels. The intrapatient variation will need to be taken into account if any of these biomarkers are used as a surrogate endpoint in research studies that employ specific interventions aimed at reducing inflammation.…”

Section: Discussionsupporting

confidence: 92%

Precision of Biomarkers to Define Chronic Inflammation in CKD

et al. 2008

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Background/Aims: Several inflammatory biomarkers have been found to be associated with cardiovascular disease or all-cause mortality in dialysis patients, but their usefulness in clinical practice or as surrogate endpoints is not certain. The purpose of the present study was to determine the intrapatient variation of C-reactive protein, IL-6, fetuin-A and albumin in a population of dialysis patients. Methods: Apparently healthy dialysis patients with either a tunneled dialysis catheter or fistula had monthly assessments of these biomarkers for a total of four determinations, and the intraclass correlation coefficients were calculated as measures of intersubject variance. Results: Our results showed large within-subject variation relative to the total variation in the measurements (31–46%). Having a tunneled catheter as opposed to a fistula was not significantly associated with mean levels, suggesting that chronic subclinical catheter infection does not explain the variation seen in the biomarkers. In contrast, there was a rapid change in these biomarkers with a clinically apparent acute infection. Conclusion: These results suggest that these biomarkers have limitations for use as surrogate endpoints in clinical trials due to wide fluctuations, even in apparently clinically healthy individuals.

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Section: Discussionsupporting

confidence: 92%

Precision of Biomarkers to Define Chronic Inflammation in CKD

et al. 2008

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“…This finding can be explained in several ways. First, inflammation occurs episodically in hemodialysis patients (43), and variation in CRP levels in prevalent HD patients was found as predicted partly by intercurrent events (44,45); therefore, the presence of chronic inflammation at a given time of observation, measured by serum IL-6 levels, may be overestimated. Second, the level of chronic inflammation in HD patients may vary over time, even during a period free of clinically apparent inflammatory events, as shown by Tsirpanlis et al (46).…”

Section: Discussionmentioning

confidence: 99%

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

Beberashvili

Sinuani

Azar

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients.Design, setting, participants, & measurements 85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 Ϯ 10.6 years, were studied after exclusion of patients with BMI Ͻ 20 kg/m 2 and/or serum albumin Ͻ35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years.Results IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 Ϯ 0.44 pg/ml per 2 yrs; P ϭ 0.001) and adjusted models (linear estimate: 2.35 Ϯ 0.57 pg/ml per 2 yrs; P ϭ 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P ϭ 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters. ConclusionsOur results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.

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“…A longitudinal study showed a significant variability in time of the inflammatory indices, but it did not examine the causes of this variability [4]. Other recent studies [8,9] have shown that common clinical events are significant inflammation-inducing factors in HD patients, but they have not distinguished persistent (in a period free of inflammatory clinical events) from the superimposed (induced by clinical events) inflammation.…”

Section: Introductionmentioning

confidence: 98%

Exploring Inflammation in Hemodialysis Patients: Persistent and Superimposed Inflammation

Tsirpanlis

Bagos²,

Ioannou³

et al. 2004

Kidney Blood Press Res

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Background: Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients. Methods: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis. Results: Fifty-one of 533 patient-weeks were positive for a clinical event. Mean ± SD (range) hs-CRP was 7.01 ± 16.06 (0.2–169) mg/l for all the weeks of the study, 38.25 ± 39.35 (2.1–169) mg/l for the weeks with clinical events and 3.70 ± 3.86 (0.2–26.1) mg/l for the weeks free of events. Variations for SAA and IL-6 were similar. ‘Clinical events’ strongly influenced acute-phase proteins and IL-6 levels. The effect of the factor ‘time’ (as assessed by inflammatory indices variation in weekly repeated measurements) was significant for all the 3 indices measured, independently of the factor ‘clinical events’. Conclusions: In periods free of clinical events, microinflammation characterizes HD patients and fluctuates in time. Inflammation due to common clinical events is added, periodically, to this microinflammation. The high level persistent microinflammation as well as the superimposed – due to clinical events – inflammation could be related to the CVD in these patients.

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Intercurrent clinical events are predictive of plasma C-reactive protein levels in hemodialysis patients

Abstract: Based on these results, both PS and CTA super-flux dialyzers appear safe for clinical use. Whether changes in CRP values, which are associated with intercurrent clinical events, influence the long-term prognosis of chronic HD patients remains to be established.

Cited by 58 publications

References 24 publications

Precision of Biomarkers to Define Chronic Inflammation in CKD

Precision of Biomarkers to Define Chronic Inflammation in CKD

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

Exploring Inflammation in Hemodialysis Patients: Persistent and Superimposed Inflammation

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