Nephrol Dial Transplant (2003) 18: 221
© 2003 European Renal Association-European Dialysis and Transplant Association
Letters
C-reactive protein levels in dialysis patients are highly variable and strongly related to co-morbidity
Department of Internal Medicine University Hospital Maastricht The Netherlands Email: jkoo{at}sint.azm.nl
Sir,
In recent literature, a strong emphasis has been placed on elevated C-reactive protein (CRP) levels as an important risk factor for morbidity and mortality [1,2]. Moreover, a relationship has been observed between elevated CRP levels, atherosclerotic plaques and malnutrition (the MIA syndrome) [3]. Nevertheless, by clinical impressions in our dialysis unit, we first noted a large variability in CRP levels and, furthermore, had the feeling that changes in CRP levels were highly related to intermittent or chronic (co-)morbidity. In the literature, data on the relationship between changes in CRP levels and intermittent morbidity are scarce [4], as are data on the variability of CRP levels per se in haemodialysis patients. The aim of the present study was to observe the variability of CRP levels and also to make an attempt to link elevated CRP levels to intermittent clinical events.
CRP levels [non-sensitive assay (Syncron LX 20; Beckham Coulter, CA); cut-off point 2 mg/l] were assessed at monthly intervals in all haemodialysis patients in our unit (n=60; mean age 68±10 years; 28 males, 32 females) over a 3 month period. Moreover, all patients were seen weekly on clinical rounds, during which special emphasis was placed on intermittent clinical events during the weekly period. If necessary, clinical rounds were followed by additional laboratory, bacteriological and radiological examinations, based on the complaints of the patients. The correlation between the CRP levels at the three time periods was assessed by Kendall's 
.
Median CRP levels at months 0, 1 and 2 were 11 mg/l (2–394), 9 mg/l (2–176) and 9 mg/l (2–565), respectively. The non-parametric correlation coefficient between CRP levels at the start of the study and 1 month later was r=0.55 (P<0.01), and 0.40 (P<0.01) for the correlation between CRP levels at the start of the study and those 2 months later. In 92% of the patients, CRP levels were >2 mg/l on at least one occasion, whereas in 68% of patients, CRP levels were >10 mg/l on at least one measurement.
In 96% of the patients with CRP levels >10 mg/l, significant clinical events and/or chronic co-morbidity were observed [acute or chronic inflammatory events (61%), malignancies (7.3%), recent surgery (4.9%), fractures (7.3%), symptomatic coronary artery disease (4.9%), active vasculitis (2.4%), gastrointestinal bleeding (2.4%)]. In contrast, in the 14 patients with CRP levels varying between 2 and 10 mg/l during the three occasions, only in one patient (7.1%) did a clinical event become apparent.
Three patients died during the study period (5%) (one myocardial infarction, one postoperative after aortic valve replacement and one terminal multiple myeloma), whereas 11 patients (18.3%) were admitted to the hospital ward.
The present data are in line with a recent observational study performed by the HEMO group, which showed a large variation in CRP levels in dialysis patients [4]. Nevertheless, in this study, variations in CRP levels were not related to clinical events.
A question that remains regards the cause of borderline elevated CRP levels. Although it cannot be proven from the present data, earlier studies showed that subclinical infections with Chlamydia pneumoniae or Helicobacter pylori were associated with mildly elevated CRP levels in dialysis patients [5,6]. Moreover, a recent study showed a relationship between elevated CRP levels and silent ischaemic heart disease in dialysis patients [7].
In conclusion, this preliminary clinical survey showed, in addition to a very high incidence of acute and chronic co-morbid events in dialysis patients, a large variation in CRP levels during a 3 month follow-up period. In nearly all patients, CRP levels >10 mg/l were associated with intermittent clinical events or severe co-morbidity, which could easily be detected with physical examination and simple additional tests. In patients with CRP levels between 2 and 10 mg/l, the association with clinical events was not clear. CRP levels >10 mg/l in dialysis patients warrant a thorough clinical examination.
References
- Yeun JY, Levine RA, Mantadilok V et al. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis2000; 35:469–476[Web of Science][Medline]
- Qureshi AR, Alvestrand A, Divino-Filho JC et al. Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol2002; 13[Suppl 1]:S28–S36[Medline]
- Stenvinkel P, Heimburger O, Paultre F et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int1999; 55:1899–1911[CrossRef][Web of Science][Medline]
- Kaysen GA, Dubin JA, Muller HG et al. The acute phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO study group. Kidney Int2000; 58:346–352[CrossRef][Web of Science][Medline]
- Aguilera A, Codoceo R, Bajo MA et al. Helicobacter pylori infections: a new cause of anorexia in peritoneal dialysis patients. Perit Dial Int2001; 21[Suppl 3]:S152–S156[Medline]
- Haubitz M, Brunkhorst R. C-reactive protein and chronic Chlamydia pneumoniae infection-long term predictors for cardiovascular disease and survival in patients on peritoneal dialysis. Nephrol Dial Transpl2001; 16:809–815
[Abstract/Free Full Text] - Kim SB, Min WK, Lee SK et al. Persistent elevation of C-reactive protein and ischemic heart disease in patients with continuous ambulatory peritoneal dialysis. Am J Kidney Dis2002; 39:342–346[Web of Science][Medline]
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