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Changes in leukocyte subsets: clinical implications for children with chronic renal failure

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Abstract

Increased systemic inflammation and an impaired immune response are features of adult chronic renal failure (CRF). These patients have increased rates of infection, cardiovascular disease, anemia, and malnutrition. We measured inflammatory and immunological markers in a group of children with pre-dialytic CRF. No prior studies have explored these markers even though children with non-dialysed CRF exhibit similar complications to those seen in adults with CRF. Blood was collected from children with mild, moderate, or severe CRF and an age-matched control group. Functional leukocyte subsets were determined using flow cytometry. Circulating levels of interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-10, and tumor necrosis factor-α were measured using a flow cytometric bead assay. Children with severe CRF showed significantly reduced total white cell count and absolute neutrophil and lymphocyte counts. Absolute numbers of CD3+/CD45RO+ memory T cells and CD3+/CD45RO+/CD62L+ memory Th2 cells were significantly reduced in all CRF groups versus controls. Children with severe CRF showed increased CD11b expression on neutrophils and monocytes. Some patients showed increases in pro-inflammatory cytokines that were not related to their level of residual renal function. As CD11b expression mediates leukocyte adhesion to vascular endothelium, upregulation may contribute to the increased endothelial dysfunction observed in children with CRF. L-selectin mediates extravasation of leukocytes into tissue and homing of peripheral blood lymphocytes to lymph nodes. The reduction in L-selectin may inhibit these actions and predispose patients to increased infection later in life. This is the first study to comprehensively investigate leukocyte functional molecules and inflammatory cytokine profiles in children with pre-dialytic CRF and provides new immunological evidence for the clinical manifestations associated with the disease.

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References

  1. Girndt M, Sester U, Sester M, Kaul H, Kohler H (1999) Impaired cellular immune function in patients with end-stage renal failure. Nephrol Dial Transplant 14:2807–2810

    Article  Google Scholar 

  2. Pereira BJ, Shapiro L, King AJ, Falagas ME, Strom JA, Dinarello CA (1994) Plasma levels of IL-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. Kidney Int 45:890–896

    Google Scholar 

  3. Ishizuka T, Nitta K, Yokoyama T, Hayashi T, Futatsuyama K, Kimata N, Miwa N, Nishida E, Kawashima A, Akiba T, Nihei H (2002) Increased serum levels of interleukin-12 may be associated with Th1 differentiation in hemodialysis patients. Nephron 90:503–504

    Article  Google Scholar 

  4. Flynn JT, Frisch K, Kershaw DB, Sedman AB, Bunchman TE (1999) Response to early measles-mumps-rubella vaccination in infants with chronic renal failure and/or receiving peritoneal dialysis. Adv Perit Dial 15:269–272

    CAS  PubMed  Google Scholar 

  5. Kaysen GA, Eiserich JP (2003) Characteristics and effects of inflammation in end-stage renal disease. Semin Dial 16:438–446

    Article  Google Scholar 

  6. Kaysen GA, Kumar V (2003) Inflammation in ESRD: causes and potential consequences. J Ren Nutr 13:158–160

    Google Scholar 

  7. Girndt M, Sester M, Sester U, Kaul H, Kohler H (2001) Molecular aspects of T- and B-cell function in uremia. Kidney Int [Suppl] 78:S206–S211

    Google Scholar 

  8. Szczepanska M, Szprynger K, Mazur, B, Szczepanski T (2002) Alphabeta and gammadelta T cell subsets in chronic renal failure in children on dialysis treatment. Pediatr Int 44:32–36

    Article  Google Scholar 

  9. Zwolinska D, Medynska A, Szprynger K, Szczepanska M (2000) Serum concentration of IL-2, IL-6, TNF-alpha and their soluble receptors in children on maintenance hemodialysis. Nephron 86:441–446

    Article  PubMed  Google Scholar 

  10. Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15:74–80

    Article  CAS  PubMed  Google Scholar 

  11. Kari JA, Donald AE, Vallance DT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L (1997) Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int 52:468–472

    CAS  PubMed  Google Scholar 

  12. Ikizler TA (2002) Epidemiology of vascular disease in renal failure. Blood Purif 20:6–10

    Article  Google Scholar 

  13. Bouts AH, Out TA, Schroder CH, Monnens LA, Nauta J, Krediet RT, Davin JC (2000) Characteristics of peripheral and peritoneal white blood cells in children with chronic renal failure, dialyzed or not. Perit Dial Int 20:748–756

    Google Scholar 

  14. Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590

    CAS  PubMed  Google Scholar 

  15. Jureidini KF, Hogg RJ, Renen MJ van, Southwood TR, Henning PH, Cobiac L, Daniels L, Harris S (1990) Evaluation of long-term aggressive dietary management of chronic renal failure in children. Pediatr Nephrol 4:1–10

    Article  Google Scholar 

  16. Moser B, Roth G, Brunner M, Lilaj T, Deicher R, Wolner E, Kovarik J, Boltz-Nitulescu G, Vychytil A, Ankersmit HJ (2003) Aberrant T cell activation and heightened apoptotic turnover in end-stage renal failure patients: a comparative evaluation between non-dialysis, haemodialysis, and peritoneal dialysis. Biochem Biophys Res Commun 308:581–585

    Google Scholar 

  17. Majewska E, Baj Z, Sulowska Z, Rysz J, Luciak M (2003) Effects of uraemia and haemodialysis on neutrophil apoptosis and expression of apoptosis-related proteins. Nephrol Dial Transplant 18:2582–2588

    Article  Google Scholar 

  18. Sester U, Sester M, Hauk M, Kaul H, Kohler H, Girndt M (2000) T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients. Nephrol Dial Transplant 15:1217–1223

    Article  Google Scholar 

  19. Tang ML, Steeber DA, Zhang XQ, Tedder TF (1998) Intrinsic differences in L-selectin expression levels affect T and B lymphocyte subset-specific recirculation pathways. J Immunol 160:5113–5121

    Google Scholar 

  20. Matsumoto Y, Shinzato T, Amano I, Takai I, Kimura Y, Morita H, Miwa M, Nakane K, Yoshikai Y, Maeda K (1995) Relationship between susceptibility to apoptosis and Fas expression in peripheral blood T cells from uremic patients: a possible mechanism for lymphopenia in chronic renal failure. Biochem Biophys Res Commun 215:98–105

    Google Scholar 

  21. Kanegane H, Kasahara Y, Niida Y, Yachie A, Sughii S, Takatsu K, Taniguchi N, Miyawaki T (1996) Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells. Immunology 87:186–190

    Article  Google Scholar 

  22. Lui VW, He Y, Falo L, Huang L (2002) Systemic administration of naked DNA encoding interleukin 12 for the treatment of human papillomavirus DNA-positive tumor. Hum Gene Ther 13:177–185

    Google Scholar 

  23. Kirii H, Niwa T, Yamada Y, Wada H, Saito K, Iwakura Y, Asano M, Moriwaki H, Seishima M (2003) Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 23:656–660

    Article  Google Scholar 

  24. Bouts AH, Krediet RT, Davin JC, Monnens LA, Nauta J, Schroder CH, Van De Winkel, JG, Out TA (2004) IGG and complement receptor expression on peripheral white blood cells in uraemic children. Nephrol Dial Transplant 19:2296–2301

    Article  Google Scholar 

  25. Prasad A, Koh KK, Schenke WH, Mincemoyer R, Csako G, Fleischer TA, Brown M, Selvaggi TA, Quyyumi AA (2001) Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. Am Heart J 142:248–253

    Article  Google Scholar 

  26. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    Article  CAS  PubMed  Google Scholar 

  27. Zoccali C (2002) Cardiorenal risk as a new frontier of nephrology: research needs and areas for intervention. Nephrol Dial Transplant 17 [Suppl] 11:50–54

    Google Scholar 

  28. Sarnak MJ, Coronado BE, Greene T, Wang SR, Kusek JW, Beck GJ, Levey AS (2002) Cardiovascular disease risk factors in chronic renal insufficiency. Clin Nephrol 57:327–335

    Google Scholar 

  29. Serrano CV Jr, Yoshida VM, Venturinelli ML, D’Amico E, Monteiro HP, Ramires JA, Luz PL da (2001) Effect of simvastatin on monocyte adhesion molecule expression in patients with hypercholesterolemia. Atherosclerosis 157:505–512

    Article  Google Scholar 

  30. Klinkhardt U, Bauersachs R, Adams J, Graff J, Lindhoff-Last E, Harder S (2003) Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther 73:232–241

    Google Scholar 

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Correspondence to Judi Nairn.

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Nairn, J., Hodge, G. & Henning, P. Changes in leukocyte subsets: clinical implications for children with chronic renal failure. Pediatr Nephrol 20, 190–196 (2005). https://doi.org/10.1007/s00467-004-1727-2

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  • DOI: https://doi.org/10.1007/s00467-004-1727-2

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