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Controlled Clinical Trial
. 2008 Sep;74(6):782-90.
doi: 10.1038/ki.2008.245. Epub 2008 Jun 11.

Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease

Sai Ram Keithi-Reddy  1 , Francesco Addabbo, Tejas V Patel, Bharati V Mittal, Michael S Goligorsky, Ajay K Singh
Affiliations
Controlled Clinical Trial

Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease

Sai Ram Keithi-Reddy et al. Kidney Int. 2008 Sep.

Abstract

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.

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Conflict of interest statement

DISCLOSURE

Dr Singh reports receiving consulting fees from Ortho Biotech Clinical Affairs/Johnson and Johnson, Amgen, Roche, Merck, Abbott, Watson and lecture fees from Ortho Biotech Clinical Affairs/Johnson and Johnson, Roche, Amgen, and Watson; serving on advisory boards for Ortho Biotech Clinical Affairs, Roche, Watson, AMAG, and Amgen; and receiving grant support from Ortho Biotech Clinical Affairs, Roche, Johnson & Johnson, Amgen, Watson. Dr Singh is the Medical Director of Dialysis Clinics Inc. Dr Goligorsky, Dr Patel, Dr Mittal, Dr Addabbo, and Dr Keithi-Reddy report no conflicts of interests.

Figures

Figure 1
Figure 1. Number of anemic patients and patients on ESAs by tertiles of CRP in CKD cohort
Among anemic subjects, 35.9% were in the third tertile whereas 33% were in the first tertile for CRP (Mantel–Haenszel test for linear association; P=0.58) (a). Fifty percentage of the anemic subjects on ESAs were in the third tertile whereas 33% of epo-naive patients were in the third tertile for CRP (Mantel–Haenszel test for linear association; P=0.013). Patients in the first and third tertiles were compared for P-value (b). CKD, chronic kidney disease; CRP, C-reactive protein; ESAs, erythropoiesis-stimulating agents.
Figure 2
Figure 2. Odds ratios for upper two quartiles for patients treated with ESAs
In all, 71.4% of the patients on ESAs were in upper two quartiles for IL-6 compared to 51.9% of ESA-naive anemic and 40.4% of non-anemic patients with unadjusted odds of 3.6 (a). In all, 76.2% of the patients on ESAs were in upper two quartiles for IL-8 compared to 59.3% of ESA-naive anemic and 34.6% of non-anemic patients with unadjusted odds of 6.0 (b). In total, 71.4% of the patients on ESAs were in upper two quartiles for TNF-α compared to 55.6% of ESA-naive anemic and 38.5% of non-anemic patients with unadjusted odds of 4.0 (c). Sixty percentage of the patients on ESAs were in the upper two quartiles for Ferritin compared to 44% of ESA-naive anemic and 48.9% of non-anemic patients with unadjusted odds of 1.5 (d). A total of 61.9% of the patients on ESAs were in the lower two quartiles for albumin compared to 77.8% of ESA-naive anemic and 34.6% of non-anemic patients with unadjusted odds of 6.0 (e). Odds ratios are for the use of ESAs. *Lower two and upper two quartiles are represented in reverse order for the convenience of readers. ESAs, erythropoiesis-stimulating agents; IL, interleukin; TNF-α, tumor necrosis factor-α.
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Comment in

References

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