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      Clinical Significance of C-Reactive Protein in Patients on Hemodialysis: A Longitudinal Study

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          Background/Aim: The levels of C-reactive protein (CRP) have been related to hypoalbuminemia and the necessity of erythropoietin in patients on maintenance hemodialysis. However, in several studies, the patients’ clinical situation is not taken into account. The aim of the present work was to analyze the relationship between CRP and serum albumin and hemoglobin and the erythropoietin resistance index (ERI) in a population of patients on chronic hemodialysis classified according to their clinical situation. Methods: In a cohort of 53 patients followed for 12 months, we analyzed the CRP level and its association with albumin and hemoglobin levels and the ERI (ratio of total weekly erythropoietin dose in units/weight to hemoglobin concentration in g/dl) at the start of the study and at 6 and 12 months thereafter. The patients were divided into three groups based on the presence of inflammatory/infectious disorders during the 4 weeks prior to CRP determination (group A) or the use of a jugular catheter (group B) or an arteriovenous fistula (group C) as vascular access for hemodialysis. Results: At baseline, the CRP levels (47.1 mg/l in group A, 30.7 mg/l in group B, and 9.4 mg/l in group C) and the ERI (23.9 in group A, 24.6 in group B, and 10.7 in group C) were higher in groups A and B than in group C (p < 0.001 for both parameters). Serum albumin (3.9 g/dl in group A, 4.1 g/dl in group B, and 4.4 g/dl in group C) and hemoglobin (10.4 g/dl in group A, 11.3 g/dl in group B, and 12 g/dl in group C) were lower in groups A and B than in group C (p < 0.05 for serum albumin and p < 0.01 for hemoglobin). In all patients, the baseline CRP level correlated with the albumin level (r = –0.3853, p < 0.01), with the hemoglobin level (r = –0.2950, p < 0.05), and with the ERI (r = 0.4378, p < 0.01). However, if we only considered the group C patients, there was no correlation between baseline CRP and albumin, hemoglobin, and ERI. Similar results were observed at 6 and 12 months. Conclusions: The CRP, albumin, and hemoglobin levels and the ERI mostly depend on the existence of ongoing inflammatory/infectious disorders and the use of a catheter as vascular access. In the absence of these clinical conditions, we could not correlate the CRP level with the other parameters. The relationship between CRP, albumin, and anemia may be an epiphenomenon

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          Most cited references 13

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          Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

          Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.
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            Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients.

            Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.
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              Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study.

              Studies in the general population suggest that low-grade inflammation, endothelial dysfunction, and platelet activation are associated with an increased risk of cardiovascular events. Markers of inflammation, endothelial dysfunction, and platelet activation were measured in 334 patients with chronic kidney disease (serum creatinine >1.47 mg/dL [>130 micromol/L] at screening) and compared with 2 age- and sex-matched control groups, 1 comprising 92 patients with coronary artery disease and the other comprising 96 apparently healthy individuals with no history of cardiovascular or kidney disease. There was evidence of low-grade inflammation in the chronic renal impairment group compared with healthy controls, with higher concentrations of C-reactive protein (3.70 versus 2.18 mg/L, P < 0.01) and fibrinogen (3.48 versus 2.67 g/L, P < 0.001) and lower serum albumin concentration (41.8 versus 44.0 g/dL [418 versus 440 g/L], P < 0.001). More severe renal impairment was associated with a trend towards higher fibrinogen and lower albumin concentrations (both P < 0.001), although there was no association with higher C-reactive protein level. As compared to healthy controls, plasma von Willebrand factor (142 versus 108 IU/dL, P < 0.001) and soluble P-selectin concentrations (57.0 versus 43.3 ng/mL, P < 0.001) were also higher in the chronic renal impairment group. More severe renal impairment was associated with a trend towards higher levels of von Willebrand factor (P < 0.001) and of soluble P selectin (P < 0.05). This cross-sectional analysis demonstrates that chronic kidney disease is associated with low-grade inflammation, endothelial dysfunction, and platelet activation, even among patients with moderate renal impairment.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                August 2005
                27 April 2005
                : 100
                : 4
                : c140-c145
                Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain
                85443 Nephron Clin Pract 2005;100:c140–c145
                © 2005 S. Karger AG, Basel

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                Page count
                Tables: 4, References: 24, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/85443
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