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  • Review Article
  • Published:

Monitoring of inflammation in patients on dialysis: forewarned is forearmed

Nature Reviews Nephrology volume 7, pages 166–176 (2011)Cite this article

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Abstract

Current evidence about the effects of inflammation on the outcomes of patients with advanced chronic kidney disease (CKD) generally originates from single measurements of inflammatory biomarkers. Patients with CKD, however, are exposed to persistent low-grade inflammation and levels of serum inflammatory markers are subjected to a substantial variability over time, being influenced by multiple processes, such as transient infections, comorbidities, and the intermittent stimulus of dialysis. Understanding and evaluating inflammation in the context of its time-dependent oscillations in renal disease fluctuation is, therefore, important. Nevertheless, the relationship between longitudinal inflammatory variation and risk prediction has so far been addressed in only a few studies, not all of which have been sufficiently powered. Consequently, uncertainty exists about how to interpret the findings of these studies in the clinical setting. The purpose of this Review is to explore the reasons and implications of variability in levels of inflammatory biomarkers in patients with uremia, specifically focusing on C-reactive protein (CRP) measurements. We also discuss the value of repeated versus single measurements of inflammation in the clinical setting and provide solutions to reduce both sample size and intraindividual variability in hypothetical, randomized controlled trials aimed at reducing CRP levels in patients undergoing hemodialysis.

Key Points

  • In patients with end-stage renal disease, inflammatory markers are subject to substantial variability over time, and are influenced by transient infections, comorbidities, and the intermittent stimulus of dialysis

  • Insufficient evidence exists about the implications of regular C-reactive protein (CRP) screening in patients undergoing dialysis; multiple measures of CRP seem to offer predictive advantages with single determinations

  • Regular CRP screening could identify short-term variation in levels of inflammatory markers associated with mortality, which could facilitate risk stratification of patients with chronic kidney disease

  • Regular CRP screening for individual patients could enable extensive exploration of underlying causes of inflammation and the assignment of appropriate treatment

  • When designing a randomized controlled trial to lower CRP level in patients on hemodialysis, sample size and intrapatient variability can be reduced by estimating inflammation at each time point with averaged measurements for each individual

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Figure 1: Intraindividual CRP variability could, in part, be genetically determined.
Figure 2: Weekly CRP variability in three selected hemodialysis patients at Karolinska University Hospital, Stockholm, Sweden.
Figure 3: Prediction of all-cause mortality with single and averaged measurements in prevalent patients undergoing hemodialysis.
Figure 4: Kaplan–Meier survival curves according to trimestral variation patterns.

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Acknowledgements

The authors wish to express their gratitude to Dr. C. A. M. van der Hoorn–van Velthoven from the library at Leiden University Medical Centre for their assistance in the literature study. C. Meuwese's research stay at Karolinska Institutet was carried out under the Erasmus agreement between Leiden University Medical Center and Karolinska Institutet. Support for that stay was obtained from the Dutch Kidney Foundation and the Jo Keur foundation of the Leiden University Medical Centre. The authors and some of the studies hereby presented were partially supported by the Westman's and Loo and Hans Ostermans' foundations, The Heart and Lung Foundation, the Swedish Medical Research Council (Vetenskapsrådet) and Centre for Gender Medicine at Karolinska Institutet.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333, AZ Leiden, The Netherlands

    Christiaan L. Meuwese & Friedo W. Dekker

  2. Division of Renal Medicine, CLINTEC, Karolinska Institutet, K56, Karolinska Hospital, Huddinge, Stockholm, Sweden

    Peter Stenvinkel

  3. Centers for Molecular and Gender Medicine, Karolinska Institutet, K56, Karolinska Hospital, Huddinge, Stockholm, Sweden

    Juan J. Carrero

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  1. Christiaan L. Meuwese
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  2. Peter Stenvinkel
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  3. Friedo W. Dekker
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  4. Juan J. Carrero
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Contributions

All authors made substantial contributions to the discussion of content, and reviewed/edited the manuscript before submission. C. L. Meuwese and J. J. Carrero wrote the article, and F. W. Dekker and P. Stenvinkel revised and developed the draft to its final form.

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Correspondence to Juan J. Carrero.

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Meuwese, C., Stenvinkel, P., Dekker, F. et al. Monitoring of inflammation in patients on dialysis: forewarned is forearmed. Nat Rev Nephrol 7, 166–176 (2011). https://doi.org/10.1038/nrneph.2011.2

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