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Vol. 30, No. 1, 2009
Issue release date: July 2009

25-Hydroxyvitamin D Deficiency and Inflammation and Their Association with Hemoglobin Levels in Chronic Kidney Disease

Kendrick J. · Targher G. · Smits G. · Chonchol M.
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Abstract

Background/Aims: There is limited information about the association of anemia with 25-hydroxyvitamin D [25(OH)D] deficiency and inflammation in the setting of decreased kidney function in the general population. Methods: We examined the association that anemia has with 25(OH)D deficiency and inflammation among 16,301 participants in the Third National Health and Nutrition Examination Survey (NHANES III). Measures of kidney function were estimated glomerular filtration rate (GFR) by using the Modification of Diet in Renal Disease equation. Results: The age-adjusted prevalence of anemia (hemoglobin <12 g/dl) at an estimated GFR of 59–30 ml/min/1.73 m2 was 17% increasing to 56% for those participants with an estimated GFR <30 ml/min/1.73 m2, while the age-adjusted prevalence of elevated C-reactive protein (CRP >0.21 mg/dl) and reduced 25(OH)D (<20 ng/ml) was 50 and 30%, respectively. After adjusting for demographics, comorbidities and laboratory results, 25(OH)D <20 ng/ml (OR: 1.17; 95% CI: 1.03–1.32; p = 0.014) and log CRP (OR: 3.63; 95% CI: 2.4–5.48 per unit increase of log CRP; p < 0.0001) were associated with hemoglobin levels <12 g/dl. Conclusion: This study provides evidence that lower 25(OH)D and higher CRP levels are independently associated with lower hemoglobin concentrations in kidney disease subjects not requiring dialysis.



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References

  1. McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, Tse TF, Wasserman B, Leiserowitz M: The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin 2004;20:1501–1510.
  2. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J: Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med 2002;162:1401–1408.
  3. Kazmi WH, Kausz AT, Khan S, Abichandani R, Ruthazer R, Obrador GT, Pereira BJ: Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis 2001;38:803–812.
  4. El-Achkar TM, Ohmit SE, McCullough PA, Crook ED, Brown WW, Grimm R, Bakris GL, Keane WF, Flack JM; Kidney Early Evaluation Program: Higher prevalence of anemia with diabetes mellitus in moderate kidney insufficiency: The Kidney Early Evaluation Program. Kidney Int 2005;67:1483–1488.
  5. McGonigle RJ, Wallin JD, Shadduck RK, Fisher JW: Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int 1984;25:437–444.
  6. Radtke HW, Claussner A, Erbes PM, Scheuermann EH, Schoeppe W, Koch KM: Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function. Blood 1979;54:877–884.
  7. Erslev AJ, Besarab A: The rate and control of baseline red cell production in hematologically stable patients with uremia. J Lab Clin Med 1995;126:283–286.
  8. Fisher JW: Mechanism of the anemia of chronic renal failure. Nephron 1980;25:106–111.
  9. 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;2:416–422.
  10. Panichi V, Migliori M, De Pietro S, Taccola D, Bianchi AM, Norpoth M, Metelli MR, Giovannini L, Tetta C, Palla R: C reactive protein in patients with chronic renal diseases. Ren Fail 2001;23:551–562.
  11. Stenvinkel P, Heimburger O, Wang T, Lindholm B, Bergstrom J, Elinder CG: High serum hyaluronan indicates poor survival in renal replacement therapy. Am J Kidney Dis 1999;34:1083–1088.
  12. Teruel JL, Marcen R, Ocaña J, Fernández-Lucas M, Rivera M, Tabernero G, Ortuño J: Clinical significance of C-reactive protein in patients on hemodialysis: a longitudinal study. Nephron Clin Pract 2005;100:c140–c145.
  13. Gunnell J, Yeun JY, Depner TA, Kaysen GA: Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 1999;33:63–72.
  14. Levin A: The treatment of anemia in chronic kidney disease: understandings in 2006. Curr Opin Nephrol Hypertens 2007;16:267–271.
  15. Chonchol M, Lippi G, Montagnana M, Muggeo M, Targher G: Association of inflammation with anaemia in patients with chronic kidney disease not requiring chronic dialysis. Nephrol Dial Transplant 2008;23:2879–2883.
  16. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R: Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006;83:754–759.
  17. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL: Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71:31–38.
  18. Chonchol M, Scragg R: 25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey. Kidney Int 2007;71:134–139.
  19. The Third National Health and Nutrition Examination Survey (NHANES III 1988–94) Reference Manual and Reports [book on CD-ROM]. Bethesda, National Center for Health Statistics, 2002.
  20. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(suppl 1):S1–S266.
  21. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS: Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41:1–12.
  22. Holick MF: Vitamin D deficiency. N Engl J Med 2007;357:266–281.
  23. Eustace JA, Astor B, Muntner PM, Ikizler TA, Coresh J: Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney Int 2004;65:1031–1040.
  24. National Center for Health Statistics: Plan and Operation of the Third National Health and Nutrition Examination Survey, 1988–94. Hyattsville, National Center for Health Statistics, 1995.
  25. Shah BV BB, Bieler GS: SUDAAN User’s Manual, version 7.5. Research Triangle Park, Research Triangle Institute, 1997.
  26. Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM, Toto R; RENAAL Study Investigators: The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int 2003;63:1499–1507.
  27. Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, Sarnak MJ: Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001;38:955–962.
  28. Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W: Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int 2003;64:610–615.
  29. Astor BC, Coresh J, Heiss G, Pettitt D, Sarnak MJ: Kidney function and anemia as risk factors for coronary heart disease and mortality: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 2006;151:492–500.
  30. Weiner DE, Tighiouart H, Vlagopoulos PT, Griffith JL, Salem DN, Levey AS, Sarnak MJ: Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 2005;16:1803–1810.
  31. Amin MG, Tighiouart H, Weiner DE, Stark PC, Griffith JL, MacLeod B, Salem DN, Sarnak MJ: Hematocrit and left ventricular mass: the Framingham Heart study. J Am Coll Cardiol 2004;43:1276–1282.
  32. Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A; CREATE Investigators: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355:2071–2084.
  33. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006;355:2085–2098.
  34. Fishbane S, Besarab A: Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets. Clin J Am Soc Nephrol 2007;2:1274–1282.
  35. Yilmaz MI, Carrero JJ, Axelsson J, Lindholm B, Stenvinkel P: Low-grade inflammation in chronic kidney disease patients before the start of renal replacement therapy: sources and consequences. Clin Nephrol 2007;68: 1–9.
  36. Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M: IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia – the good, the bad, and the ugly. Kidney Int 2005;67:1216–1233.
  37. Suliman ME, Heimbürger O, Bárány P, Anderstam B, Pecoits-Filho R, Rodríguez Ayala E, Qureshi AR, Fehrman-Ekholm I, Lindholm B, Stenvinkel P: Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy. J Am Soc Nephrol 2003;14:1614–1622.
  38. Stenvinkel P, Pecoits-Filho R, Lindholm B: Coronary artery disease in end-stage renal disease: no longer a simple plumbing problem. J Am Soc Nephrol 2003;14:1927–1939.
  39. Barany P, Divino Filho JC, Bergstrom J: High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients. Am J Kidney Dis 1997;29:565–568.
  40. Tonelli M, Blake PG, Muirhead N: Predictors of erythropoietin responsiveness in chronic hemodialysis patients. ASAIO J 2001;47:82–85.
  41. Kwack C, Balakrishnan VS: Managing erythropoietin hyporesponsiveness. Semin Dial 2006;19:146–151.
  42. Holick MF: Vitamin D for health and in chronic kidney disease. Semin Dial 2005;18:266–275.
  43. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ: Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders. QJM 2002;95:787–796.
  44. Balkwill FR, Burke F: The cytokine network. Immunol Today 1989;10:299–304.
  45. Johnson CS, Cook CA, Furmanski P: In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): reversal with exogenous erythropoietin (EPO). Exp Hematol 1990;18:109–113.
  46. Goicoechea M, Martin J, de Sequera P, Quiroga JA, Ortiz A, Carreño V, Caramelo C: Role of cytokines in the response to erythropoietin in hemodialysis patients. Kidney Int 1998;54:1337–1343.


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