Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor-α are similarly associated with survival in haemodialysis patients.
BACKGROUND
The impact of intra-individual changes of inflammatory markers [other than C-reactive protein (CRP)] on mortality in haemodialysis (HD) patients is unknown. We therefore studied survival in relation to trimestral variations of CRP, interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α).


METHODS
In 201 prevalent HD patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease cohort, serum CRP, IL-6 and TNF-α were measured 3 months apart and survival was assessed during follow-up. Based on fluctuations along tertiles of distribution, four patterns were defined for each inflammatory marker: stable low, decrease, increase and stable high. Hazard ratios were calculated by the Cox proportional hazard model, and Pearson's test was used to correlate changes. CRP analyses were replicated in 472 incident HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis.


RESULTS
Patients with persistently elevated CRP values had the worst mortality in crude [HR 2.98 (95% CI 1.71-5.20)] and adjusted [2.79 (1.58-4.94)] Cox models, together with those who increased in their CRP levels [crude 3.27 (1.91-5.60); adjusted 3.13 (1.79-5.45)]. Similar survival patterns were observed for IL-6 and TNF-α variation categories. Correlations among these changes were, however, not strong. In the replication cohort, individuals with persistently elevated CRP values also showed the highest mortality risk [crude 3.38 (2.31-4.94); adjusted 2.33 (1.58-3.45)].


CONCLUSIONS
Trimestral variations of TNF-α, IL-6, and CRP are similarly associated with survival in HD patients. The agreement between changes of these biomarkers was low, suggesting that different pathways may trigger each of these markers.
Meuwese
Christiaan L
CL
Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
Snaedal
Sunna
S
Halbesma
Nynke
N
Stenvinkel
Peter
P
Dekker
Friedo W
FW
Qureshi
Abdul R
AR
Barany
Peter
P
Heimburger
Olof
O
Lindholm
Bengt
B
Krediet
Raymond T
RT
Boeschoten
Els W
EW
Carrero
Juan J
JJ
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein