NDT Advance Access originally published online on October 25, 2005
Nephrology Dialysis Transplantation 2006 21(3):749-755; doi:10.1093/ndt/gfi204
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients
1 Division of General Internal Medicine and Nephrology, Department of Internal Medicine, Robert-Bosch Hospital, 2 Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, 3 Dialysis Center Stuttgart and 4 Dialysis Center Dürrlewang, Stuttgart, Germany, 5 Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital Zuerich, Zuerich, Switzerland, 6 Division of Psychosomatic Medicine, Department of Internal Medicine, Robert-Bosch-Hospital, Stuttgart, Germany and 7 Division of Nephrology, Department of Internal Medicine, Deutsche Klinik für Diagnostik, Wiesbaden, Germany
Correspondence and offprint requests to: Martin Kimmel, Robert-Bosch-Krankenhaus, Auerbachstr. 110, D-70376 Stuttgart, Germany. Email: vm.kimmel{at}t-online.de
Background. Uraemic pruritus (UP) is still one of the most vexing and disabling symptoms in chronic renal failure. The pathogenesis of UP is obscure and effective therapeutic strategies are elusive. Deduced from partial successful treatment modalities, there is evidence that an alteration of the immune system with a pro-inflammatory pattern along with a deranged T-helper-cell differentiation may be involved in the pathogenesis of UP. We, therefore, investigated whether UP is related to an augmented Th1-differentiation as measured by determination of intracytoplasmatic (i.c.) cytokines and expression of chemokine receptors. Additionally, pro-inflammatory cytokines were determined in serum.
Methods. In a multicentre study, 171 patients on haemodialysis (HD) were screened for UP. Finally, 13 HD patients with and 13 HD patients without UP, as well as 15 healthy controls were enrolled in the study. Peripheral blood mononuclear cells were isolated and the proportion of Th1- and Th2-cells was determined by flow cytometry. The expression of chemokine receptors on CD4 cells (CXCR3 preferentially on Th1 and CCR4 on Th2) and i.c. cytokines (IFN
for Th1 and IL4 for Th2) were measured after in vitro stimulation. Serum cytokine levels (IL6 and TNF
) and CRP were measured by ELISA.
Results. Compared to HD patients without UP, those complaining of UP showed a significantly enhanced proportion of Th1-cells as measured by both techniques. Additionally, serum CRP and IL6 levels were significantly higher in HD patients with UP, compared to HD patients without UP.
Conclusions. These results point to a central role of inflammation in the pathogenesis of UP in HD patients.
Keywords: CRP; cytokines; inflammation; Th1/Th2; uraemic pruritus
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