Background: Several studies have provided convincing evidence that in apparently healthy subjects elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death. It has been claimed that, in dialytic patients, the hepatic synthesis of this ‘acute phase response’ plasma protein is primarily induced by the macrophage-derived interleukin 6 (IL-6). Little information is available, however, regarding CRP and IL-6 plasma levels in pre-dialytic renal failure. Methods: Plasma CRP by a modification of the laser nephelometry technique, IL-6 and serum albumin were determined in 103 chronic pre-dialytic patients (mean age 50 ± 6.3 years; creatinine clearance (Cr.cl.) 36.3 ± 23.1 ml/min). Results: CRP was >5 mg/l (normal upper range) in 42% of the global population. CRP and IL-6 were significantly related (r = 0.35, p < 0.0004). CRP and IL-6 were related to renal function (CRP vs. Cr.cl., r = –0.56, p < 0.0001; IL-6 vs. Cr.cl., r = –0.55, p < 0.0001, Spearman correlation coefficient). When patients were divided in tertiles according to renal function, CRP median value resulted 7.9 mg/l (interquartile interval: 5–12) in the first tertile (Cr.cl. <18.5 ml/min), 4.0 mg/l (3–6) in the second tertile (Cr.cl. 18.5–45 ml/min) and 3.2 mg/l (2.7–4.0) in the last tertile (Cr.cl. >45 ml/min) (p < 0.0001). A negative correlation between CRP and S-albumin was also found (r = –0.52, p < 0.0001, Spearman correlation coefficient). Conclusions: IL-6 and CRP were increased and were inversely related to creatinine clearance in our population of 103 chronic predialytic patients. The possibility of a decreased renal clearance of CRP and/or cytokines as a cause of an activated acute-phase response is discussed. A negative correlation between CRP and S-albumin was found confirming the link between chronic inflammation and malnutrition in chronic renal patients.

Keywords:
Chronic inflammation, C-reactive protein, Interleukin-6, Pre-dialytic chronic renal failure
1.
Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899–1911.
2.
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healty men. N Engl J Med 1997;336(14):973–979.
3.
Kushner I: The phenomenon of the acute phase response. Ann N Y Acad Sci 1982;389:39–48.
4.
Ganapathi MK, May LT, Schultz D, et al: Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun 1988;157:271–277.
5.
Lindhal B, Toss H, Siegbahn A, Venge P, Wallentin L: Markers of myocardial damage and inflammation in relation to long term mortality in unstable coronary artery disease. FRISC Study Group. Fragmnin during instability in Coronary Artery Disease. N Engl J Med 2000;343(16):1139–47.
6.
Lagrand WK, Cees A, Visser CA, Hermens WT, Niessen JWM, Freek WA, Verheug FWA, Wolbink GJ, Hack CE: C-reactive protein as a cardiovascular risk. More than an epiphenomenon? Circulation 1999;100:96–102.
7.
Kaysen G, Rathore V, Shearer GC, Depner TA: Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int 1995;48:510–516.
8.
Barany P, Divino Fiho JC, Bergstrom J: High C-reactive protein is a strong predictor to erythropoietin in hemodialysis patients. Am J Kidney Dis 1997;29(4):565–568.
9.
Haubitz M, Brunkhorst R, Wrenger E, Foese P, Shughltze M, Koch KM: Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal dialysis therapy. Perit Dial Int 1996;16(2):158–162.
10.
Iseki K, Tozawa M, Yoshi S, Fukiyama K: Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999;14:1965–1960.
11.
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C: Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648–658.
12.
Noh H, Lee SW, Kang SW, Shin SK, Chol KH, Lee HY, Han DS: Serum C-reactive protein: A predictor of mortality in continous ambulatory peritoneal dialysis patients. Perit Dial Int 1998;18:387–394.
13.
Ikizler TA, Wingard RL, Harvell J, Shyr Y, Hakim RM: Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: A prospective study. Kidney Int 1999;55:1945–1951.
14.
Stenvinkel P, Heimburger O, Wang T, Lindholm B, Bergstrom J, Elinder C: High serum hyaluronan indicates poor survival in renal replacement therapy. Am J Kidney Dis 1999;34:1083–1088.
15.
Maseri A: Inflammation, atherosclerosis and ischemic events – Exploring the hidden side of the moon. N Engl J Med 1997;336(14):1014–1016.
16.
Kushner I, Broder ML, Karp D: Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest 1978;61:235–242.
17.
Lagrand WK, Niessen JWM, Wolbink GJ, Jaspar EH, Visser CA, Verheug FWA, Mejer CJLM, Hack CE: C-reactive protein sites colocalized with complement in human hearts during acute myocardial infarction. Circulation 1997;95:97–103.
18.
Bemelmans MH, Gouma DJ, Bourman WA: Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J Immunol 1993;150:2007–2017.
19.
Descamps-Latscha B, Herbelin A, Nguyen AT, Rox-Lombard P, Zingraff J, Moynot A, Verger C, Dahmane D, de Groote D, Jungers P, et al: Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationship with activation markers of T cells, B cells and monocytes. J Immunol 1995;154:882–892.
20.
Poole S, Bird TA, Selkirk S, Gaines-Das RE, Choudry Y, Stephenson SL, Kenny AJ, Saklatvaa J: Fate of injected interleukin 1 in rats; sequestration and degradation in the kidney. Cytokine 1990;6:416–422.
21.
Miyata T, Wada Y, Cai Z, Iida Y, Horie K, Yasuda Y, Maeda K, Kurokawa K, van Ypersele de Strihou C: Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure. Kidney Int 1997;51:1170–1181.
22.
Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen AN, Zingraff J, Jungers P, Descamps-Latscha B: Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996;49:1304–1313.
23.
Hofmann M, Drury S, Fu C, Wu Q, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM: RAGE mediates a novel proinflammatory axis: A central cell surface receptor for S100/calgranulin polypeptides. Cell 1999;97:889–901.
24.
Schwedler S, Schinzel R, Vaith P, Wanner C: Inflammation and advanced glycation end products inuremia: simple coexistence, potentiation or causal relationship? Kidney Int 2001;59:S78, 32–36.
25.
Steiman TI: Serum albumin: Its significance in patients with ESRD. Semin Dial 2000;13:404–408.
26.
Kaizu Y, Kimura M, Yoneyama T, Miyajl K, Hibi I, Kumagai H. Interleukin-6 may mediate malnutrition in chronic hemodialysis patients. Am J Kidney Dis 1998;31(1):93–100.
27.
Bologa RM, Levine DM, Parker TS, Cheig JS, Serur D, Stenkel KH, Rubin AL: Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis 1998;32(1):107–114.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.