The hallmark of the Cardiff contribution to our understanding of peritoneal dialysis over the past quarter century has been their translational approach to research, combining strong basic science with intelligent clinical questions. Their themes have included describing the biology of the dialyzed membrane; elucidation of several overlapping mechanisms of bioincompatibility, resulting in the development and testing of more biocompatible solutions; and describing the morphological changes with time on treatment and the membrane's response to infection. This has extended to investigation of the mechanisms controlling initiation and resolution by the innate immune system, relevant to both long-term membrane injury and a wider understanding of immunobiology. More than any other group, they have held the torch for basic science in peritoneal dialysis research.
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BeavisM.J., WilliamsJ.D., HoppeJ., TopleyN.Human peritoneal fibroblast proliferation in 3-dimensional culture: modulation by cytokines, growth factors and peritoneal dialysis effluent.Kidney Int1997; 51: 205–15.
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LiF.K., DavenportA., RobsonR.L., LoetscherP., RothleinR., WilliamsJ.D.Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression.Kidney Int1998; 54: 2170–83.
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LiberekT., Lichodziejewska-NiemierkoM., Knopinska-PoslusznyW., SchaubT.P., KirchgessnerJ., Passlick-DeetjenJ.Generation of TNFalpha and interleukin-6 by peritoneal macrophages after over night dwells with bicarbonate- or lactate-buffered dialysis fluid.Perit Dial Int2002; 22: 663–9.
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WongT.Y., PhillipsA.O., WitowskiJ., TopleyN.Glucose-mediated induction of TGF-beta 1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent.Kidney Int2003; 63: 1404–16.
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MackenzieR., HolmesC.J., JonesS., WilliamsJ.D., TopleyN.Clinical indices of in vivo biocompatibility: the role of ex vivo cell function studies and effluent markers in peritoneal dialysis patients.Kidney Int Suppl2003 (88): S84–93.
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WilliamsJ.D., CraigK.J., TopleyN., Von RuhlandC., FallonM., NewmanG.R.Morphologic changes in the peritoneal membrane of patients with renal disease.J Am Soc Nephrol2002; 13: 470–9.
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WilliamsJ.D., CraigK.J., TopleyN., WilliamsG.T.Peritoneal dialysis: changes to the structure of the peritoneal membrane and potential for biocompatible solutions.Kidney Int2003; 63: 158–61.
21.
ColesG.A., GokalR., OggC., JaniF., O'DonoghueD.T., CancariniG.C.A randomized controlled trial of a bicarbonate-and a bicarbonate/lactate-containing dialysis solution in CAPD.Perit Dial Int1997; 17: 48–51.
WilliamsJ.D., TopleyN., CraigK.J., MackenzieR.K., PischetsriederM., LageC.The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane.Kidney Int2004; 66: 408–18.
MacKenzieR.K., HolmesC.J., MoseleyA., JenkinsJ.P., WilliamsJ.D., ColesG.A.Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.J Am Soc Nephrol1998; 9: 1499–506.
26.
MackenzieR.K., ColesG.A., WilliamsJ.D.The response of human peritoneal macrophages to stimulation with bacteria isolated from episodes of continuous ambulatory peritoneal dialysis-related peritonitis.J Infect Dis1991; 163: 837–42.
27.
WitowskiJ., JorresA., ColesG.A., WilliamsJ.D., TopleyN.Superinduction of IL-6 synthesis in human peritoneal mesothelial cells is related to the induction and stabilization of IL-6 mRNA.Kidney Int1996; 50: 1212–23.
28.
HurstS.M., WilkinsonT.S., McLoughlinR.M., JonesS., HoriuchiS., YamamotoN.Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation.Immunity2001; 14: 705–14.
29.
HurstS.M., McLoughlinR.M., MonslowJ., OwensS., MorganL., FullerG.M.Secretion of oncostatin M by infiltrating neutrophils: regulation of IL-6 and chemokine expression in human mesothelial cells.J Immunol2002; 169: 5244–51.
30.
EberlM., RobertsG.W., MeuterS., WilliamsJ.D., TopleyN., MoserB.A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections.PLoS Pathog2009; 5: e1000308.
31.
RobertsG.W., BairdD., GallagherK., JonesR.E., PepperC.J., WilliamsJ.D.Functional effector memory T cells enrich the peritoneal cavity of patients treated with peritoneal dialysis.J Am Soc Nephrol2009; 20: 1895–900.
32.
JonesG.W., McLoughlinR.M., HammondV.J., ParkerC.R., WilliamsJ.D., MalhotraR.Loss of CD4+ T cell IL-6R expression during inflammation underlines a role for IL-6 trans signalling in the local maintenance of Th17 cells.J Immunology2010; 184: 2130–9.
