%0 Journal Article
%~ PubMed
%A Tian, Xinrui
%A Zhang, Jianlin
%A Tan, Thian Kui
%A Lyons, J Guy
%A Zhao, Hong
%A Niu, Bo
%A Lee, So Ra
%A Tsatralis, Tania
%A Zhao, Ye
%A Wang, Ya
%A Cao, Qi
%A Wang, Changqi
%A Wang, Yiping
%A Lee, Vincent W S
%A Kahn, Michael
%A Zheng, Guoping
%A Harris, David C H
%T Association of β-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1.
%B Journal of Cell Science
%D 2013
%C United Kingdom
%I The Company of Biologists Ltd.
%V 126
%N Pt 1
%P 67-76
%@ 1477-9137
%X 
%Z FOR Codes: 601


%0 Journal Article
%~ PubMed
%A Wang, Ya
%A Wang, Yuan Min
%A Wang, Yiping
%A Zheng, Guoping
%A Zhang, Geoff Yu
%A Zhou, Jimmy Jianheng
%A Tan, Thian Kui
%A Cao, Qi
%A Hu, Min
%A Watson, Debbie
%A Wu, Huiling
%A Zheng, Dong
%A Wang, Changqi
%A Lahoud, Mireille H
%A Caminschi, Irina
%A Harris, David C
%A Alexander, Stephen I
%T DNA vaccine encoding CD40 targeted to dendritic cells in situ prevents the development of Heymann nephritis in rats.
%B Kidney International
%D 2013
%C United Kingdom, United States
%I Nature Publishing Group
%V 83
%N 2
%P 223-232
%@ 0085-2538
%X 
%Z FOR Codes: 110703


%0 Journal Article
%~ PubMed
%A Wang, Yuan Min
%A Zhang, Geoff Yu
%A Hu, Min
%A Polhill, Tania
%A Sawyer, Andrew
%A Zhou, Jimmy Jianheng
%A Saito, Mitsuru
%A Watson, Debbie
%A Wu, Huiling
%A Wang, Ya
%A Wang, Xin Maggie
%A Wang, Yiping
%A Harris, David C H
%A Alexander, Stephen I
%T CD8+ Regulatory T Cells Induced by T Cell Vaccination Protect Against Autoimmune Nephritis.
%B Journal of the American Society of Nephrology
%D 2012
%C United States
%I Ovid
%V 23
%N 6
%P 1058-1067
%@ 1533-3450
%X Autoreactive T cells play a pivotal role in the pathogenesis of autoimmune kidney disease. T cell vaccination (TCV) may limit autoimmune disease and induce CD8+ regulatory T cells (Tregs). We used Heymann nephritis (HN), a rat model of human membranous nephritis, to study the effects of TCV on autoimmune kidney disease. We harvested CD4+ T cells from renal tubular antigen (Fx1A) -immunized rats and activated these cells in vitro to express the MHC Class Ib molecule Qa-1. Vaccination of Lewis rats with these autoreactive Fx1A-induced T cells protected against HN, whereas control-primed T cells did not. Rats that underwent TCV had lower levels of proteinuria and serum creatinine and significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates. Furthermore, these rats expressed less IFN-?? and IL-6 in splenocytes, whereas the numbers of Tregs and the expression of Foxp3 were unchanged. In vitro cytotoxicity assays showed CD8+ T cell-mediated elimination of Qa-1-expressing CD4+ T cells. In vivo, TCV abrogated the increase in Qa-1-expressing CXCR5+ TFH cells observed in HN compared with controls. Taken together, these results suggest that TCV protects against autoimmune kidney disease by targeting Qa-1-expressing autoreactive CD4+ cells.
%Z FOR Codes: 110703


%0 Journal Article
%~ PubMed
%A Zhou, Jimmy Jianheng
%A Wang, Yuan Min
%A Lee, Vincent Ws
%A Phoon, Richard Ks
%A Zhang, Geoff Yu
%A Wang, Ya
%A Tan, Thian Kui
%A Hu, Min
%A Wang, Lucy Dongwei
%A Saito, Mitsuru
%A Sawyer, Andrew
%A Harris, David C H
%A Alexander, Stephen I
%A Durkan, Anne M
%T DEC205-DC targeted DNA vaccines to CX3CR1 and CCL2 are potent and limit macrophage migration.
%B International Journal of Clinical and Experimental Medicine
%D 2012
%C United States
%I E-Century Publishing Corporation
%V 5
%N 1
%P 24-33
%@ 1940-5901
%X Monocytes utilise a variety of chemokines to traffic to atherosclerotic plaques. CX3C chemokine ligand 1 (CX3CL1 & Fractalkine) and its receptor CX3CR1 and monocyte chemoattractant protein 1 (CCL2) have been identified as chemokines/receptors that have an important role in the migration and recruitment of monocytes during the pathogenesis of several inflammatory diseases including atherosclerosis. DNA vectors containing single chain variable region fragment (scFv) for DC-targeted receptor DEC205 were cloned with mouse CX3CR1 and CCL2 genes respectively, and vaccinated into C57/BL6 mice weekly for 3 weeks. Induced anti-CX3CR1 and anti-CCL2 in vaccinated mice was examined by ELISA and Western Blot analysis, while the cellular response was examined by ELISPOT. The inhibition of chemotaxis of J774 macrophages to Py-4-1 endothelial cells was examined by in vitro transwell migration assay using serum collected from vaccinated mice. All vaccinated mice generated anti-CX3CR1 and anti-CCL2 Ab and cellular response by 8 weeks after DNA vaccination. Macrophage migration towards TNF-? activated endothelial cells was significantly inhibited by serum containing both anti-CX3CR1 or anti-CCL2 Ab from vaccinated mice. These results demonstrate that DC-targeting of DNA vaccines to self-antigens generates functional immune responses which can inhibit specific key chemotactic targets. This suggests a potential therapeutic role for chemokine/receptor DNA vaccination in atherosclerosis, where chemotaxis has a pivotal role in the inflammatory process.
%Z FOR Codes: 110704 111601 110705


%0 Journal Article
%~ PubMed
%A Johnson, David W
%A Wong, Muh Geot
%A Cooper, Bruce A
%A Branley, Pauline
%A Bulfone, Liliana
%A Collins, John F
%A Craig, Jonathan C
%A Fraenkel, Margaret B
%A Harris, Anthony
%A Kesselhut, Joan
%A Li, Jing Jing
%A Luxton, Grant
%A Pilmore, Andrew
%A Tiller, David J
%A Harris, David C
%A Pollock, Carol A
%T Effect of timing of dialysis commencement on clinical outcomes of patients with planned initiation of peritoneal dialysis in the ideal trial.
%B Peritoneal Dialysis International
%D 2012
%C Canada
%I Multimed, Inc.
%V 32
%N 6
%P 595-604
%@ 1718-4304
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Polhill, Tania
%A Zhang, Geoff Yu
%A Hu, Min
%A Sawyer, Andrew
%A Zhou, Jimmy Jianheng
%A Saito, Mitsuru
%A Webster, Kylie E
%A Wang, Ya
%A Wang, Yiping
%A Grey, Shane T
%A Sprent, Jonathan
%A Harris, David C H
%A Alexander, Stephen I
%A Wang, Yuan Min
%T IL-2/IL-2Ab Complexes Induce Regulatory T Cell Expansion and Protect against Proteinuric CKD.
%B Journal of the American Society of Nephrology
%D 2012
%C United States
%I Ovid
%V 23
%N 8
%P 1303-1308
%@ 1533-3450
%X Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease.
%Z FOR Codes: 110703


%0 Journal Article
%~ PubMed
%A Zheng, Dong
%A Cao, Qi
%A Lee, Vincent W S
%A Wang, Ya
%A Zheng, Guoping
%A Wang, Yuanmin
%A Tan, Thian Kui
%A Wang, Changqi
%A Alexander, Stephen I
%A Harris, David C H
%A Wang, Yiping
%T Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease.
%B Kidney International
%D 2012
%C United Kingdom, United States
%I Nature Publishing Group
%V 81
%N 9
%P 892-902
%@ 0085-2538
%X Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.Kidney International advance online publication, 8 February 2012; doi:10.1038/ki.2011.471.
%Z FOR Codes: 110704 111601 110707


%0 Book Section
%A Zheng, Guoping
%A Zhang, Jianlin
%A Tan, Thian Kui
%A Hsu, Tzu-Ting
%A Tian, Xinrui
%A Niu, Bo
%A Harris, David
%T Matrix Metalloproteinases (MMPs) in Renal Fibrosis
%B Matrix Metalloproteinases: Biology, Functions and Clinical Implications
%D 2012
%C United States
%I Nova Science Publishers
%V 
%N 
%P 171-188
%@ 9781621007890
%X 
%Z FOR Codes: 110106


%0 Journal Article
%~ PubMed
%A Wang, Yuan Min
%A McRae, Jennifer L
%A Robson, Simon C
%A Cowan, Peter J
%A Zhang, Geoff Yu
%A Hu, Min
%A Polhill, Tania
%A Wang, Yiping
%A Zheng, Guoping
%A Wang, Ya
%A Lee, Vincent W S
%A Unwin, Robert J
%A Harris, David C H
%A Dwyer, Karen M
%A Alexander, Stephen I
%T Regulatory T cells participate in CD39-mediated protection from renal injury.
%B European Journal of Immunology
%D 2012
%C Germany
%I Wiley - VCH Verlag GmbH & Co. KGaA
%V 42
%N 9
%P 2441-2451
%@ 0014-2980
%X CD39 is an ecto-enzyme that degrades extracellular nucleotides, such as ATP, and is highly expressed on by the vasculature and circulating cells including Foxp3+ regulatory T (Treg) cells. To study the role of purinergic regulation in renal disease, we used the adriamycin nephropathy (AN) mouse model of chronic renal injury, using human CD39-transgenic (hCD39Tg) and wild-type (WT) BALB/c mice. Effects of CD39 expression by Treg cells were assessed in AN by adoptive transfer of CD4+CD25+ and CD4+CD25- T cells isolated from hCD39Tg and WT. hCD39Tg mice were protected from renal injury in AN with decreased urinary protein and serum creatinine, and significantly less renal injury compared with WT. While WT CD25+ and hCD39Tg CD25- T cells conferred some protection against AN, hCD39Tg CD25+ Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, hCD39 expressed by circulating leukocytes and intrinsic renal cells limits innate AN injury. Specifically CD39 expression by Treg cells contributes to its protective role in renal injury. These findings suggest that extracellular nucleotides mediate AN kidney injury and that CD39, expressed by Treg cells and other cells, is protective in this model.
%Z FOR Codes: 110703


%0 Journal Article
%~ PubMed
%A Myint, Thida M M
%A Cooper, Bruce A
%A Pollock, Carol A
%A Harris, David C H
%T Starting Dialysis Early: No Survival, Quality of Life, or Cost Advantages.
%B Seminars in Dialysis
%D 2012
%C United States
%I Wiley-Blackwell Publishing, Inc.
%V 25
%N 5
%P 522-523
%@ 1525-139X
%X 
%Z FOR Codes: 110312


%0 Journal Article
%A Harris, David
%A Dupuis, Sophie
%A Couser, William G
%A Feehally, John
%T Training nephrologists from developing countries: does it have a positive impact?
%B Kidney International Supplements
%D 2012
%C United States
%I Nature Publishing Group
%V 2
%N 
%P 275-278
%@ 2157-1724
%X 
%Z FOR Codes: 130209 110312


%0 Journal Article
%~ PubMed
%A Pollock, Carol A
%A Cooper, Bruce A
%A Harris, David C
%T When should we commence dialysis? The story of a lingering problem and today's scene after the IDEAL study.
%B Nephrology, Dialysis, Transplantation
%D 2012
%C United Kingdom
%I Oxford University Press
%V 27
%N 6
%P 2162-2166
%@ 1460-2385
%X Over the last 15-20 years, there has been an increasing trend for dialysis to be commenced earlier in the development of chronic kidney disease (CKD). The drivers for initiation of dialysis at higher levels of renal function are complex but were primarily based on the assumption that by improving solute and water clearances with earlier dialysis, morbidity, mortality and quality of life would be improved. The Initiating Dialysis Early and Late (IDEAL) trial definitively demonstrated that elective earlier initiation of dialysis was not associated with improved clinical outcomes or quality of life. Indeed, no subset of patients was found to benefit from earlier dialysis. Observational data suggests that patients who commence dialysis with higher levels of renal function are more likely to have significant comorbidity that results in higher mortality rates compared to patients who remain clinically well and biochemically stable and are able to defer the initiation of dialysis till later in the course of CKD. However, patients who are able to defer dialysis should have appropriate access created so as to avoid the use of temporary catheters and to facilitate initiation using the preferred dialysis modality. Estimates of glomerular filtration rates in Stage 5 CKD have been poorly validated and should not be used as the key determinant influencing the commencement of dialysis. The results of the IDEAL trial have influenced guidelines internationally and provide clinicians, patients and health care providers with important information to drive clinical decision making and rational service planning.
%Z FOR Codes: 110312 111717


%0 Journal Article
%~ PubMed
%A Harris, David
%T A new admiral for the flagship.
%B Kidney International
%D 2011
%C United Kingdom, United States
%I Nature Publishing Group
%V 80
%N 9
%P 899
%@ 0085-2538
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Lee, Vincent Ws
%A Harris, David Ch
%T Adriamycin nephropathy: A model of focal segmental glomerulosclerosis.
%B Nephrology
%D 2011
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 16
%N 1
%P 30-38
%@ 1440-1797
%X Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of chronic proteinuric renal disease. AN is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a number of loci that alter both risk and severity of renal injury induced by Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to be modulated by both non-immune and immune factors, and has facilitated further study of mechanisms of tubulointerstitial injury. This review will outline the pharmacological behaviour of Adriamycin, and describe in detail the model of AN, including its key structural characteristics, genetic susceptibility and pathogenesis.
%Z FOR Codes: 111699 110704


%0 Journal Article
%~ PubMed
%A Li, Philip Kam-Tao
%A Chow, Kai Ming
%A Matsuo, Seiichi
%A Yang, Chih Wei
%A Jha, Vivekanand
%A Becker, Gavin
%A Chen, Nan
%A Sharma, Sanjib Kumar
%A Chittinandana, Anutra
%A Chowdhury, Shafiqul
%A Harris, David Ch
%A Hooi, Lai Seong
%A Imai, Enyu
%A Kim, Suhnggwon
%A Kim, Sung Gyun
%A Langham, Robyn
%A Padilla, Benita S
%A Teo, Boon Wee
%A Togtokh, Ariunaa
%A Walker, Rowan G
%A Wang, Hai Yan
%A Tsukamoto, Yusuke
%T Asian Chronic Kidney Disease (CKD) Best Practice Recommendations - Positional Statements for Early Detection of CKD from Asian Forum for CKD Initiatives (AFCKDI).
%B Nephrology (Carlton, Vic.)
%D 2011
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 16
%N 7
%P 633-41
%@ 1440-1797
%X 
%Z FOR Codes: 1103


%0 Journal Article
%~ PubMed
%A Gopinath, Bamini
%A Harris, David C
%A Flood, Victoria M
%A Burlutsky, George
%A Brand-Miller, Jennie
%A Mitchell, Paul
%T Carbohydrate nutrition is associated with the 5-year incidence of chronic kidney disease.
%B Journal of Nutrition
%D 2011
%C United States
%I American Society for Nutrition
%V 141
%N 3
%P 433-439
%@ 1541-6100
%X It has been shown that dietary glycemic index (GI) and fiber could have a role in the development of chronic diseases; however, the link between carbohydrate nutrition and development of chronic kidney disease (CKD) is unclear. We aimed to determine whether cross-sectional and longitudinal associations exist between carbohydrate nutrition (mean dietary GI, dietary intakes of carbohydrate, sugar, starch, and fiber) and CKD. Data included 2600 Blue Mountains Eye Study (1997-1999) participants aged ???50 y. Baseline biochemistry including serum creatinine was measured. Moderate CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL??min(-1)??1.73 m(-2). Dietary data were collected in a semiquantitative FFQ. Cross-sectionally, participants in the 4th quartile of mean dietary GI intake compared with those in the first quartile (reference) had a 55% increased likelihood of having eGFR < 60 mL??min(-1)??1.73 m(-2) [multivariable-adjusted OR = 1.55 (95% CI = 1.07-2.26); P-trend = 0.01]. After multivariable adjustment, participants in the 4th quartile of dietary cereal fiber intake compared with those in the first quartile (reference) had a 50% reduced risk of incident moderate CKD (P-trend = 0.03). Higher baseline consumption of energy-dense, nutrient-poor sources of carbohydrate (e.g. cookies) yielded a 3-fold higher risk of incident CKD (P-trend = 0.01). In summary, we observed a novel link between high cereal fiber intake and reduced incidence of moderate CKD and this was supported by the cross-sectional association with dietary GI. Conversely, our data suggest that higher intake of energy-dense, nutrient-poor sources of carbohydrate, potentially through acute hyperglycemia, could impair renal function.
%Z FOR Codes: 111101 110312


%0 Journal Article
%~ PubMed
%A Gopinath, Bamini
%A Harris, David C
%A Flood, Victoria M
%A Burlutsky, George
%A Mitchell, Paul
%T Consumption of long-chain n-3 PUFA, &#945;-linolenic acid and fish is associated with the prevalence of chronic kidney disease.
%B British Journal of Nutrition
%D 2011
%C United Kingdom
%I Cambridge University Press
%V 105
%N 9
%P 1361-1368
%@ 0007-1145
%X Due to the anti-inflammatory properties of PUFA, it has been suggested that they may protect against kidney damage in adults. However, relatively few epidemiological studies have examined this hypothesis in human subjects. We investigated the association between dietary intakes of PUFA (n-3, n-6 and ??-linolenic acid), fish and the prevalence of chronic kidney disease (CKD). A total of 2600 Blue Mountains Eye Study (1997-9) participants aged ?????50 years were analysed. Dietary data were collected using a semi-quantitative FFQ, and PUFA and fish intakes were calculated. Baseline biochemistry including serum creatinine was measured. Moderate CKD was defined as an estimated glomerular filtration rate of <??60??ml/min per 1??73??m2. Participants in the highest quartile of long-chain n-3 PUFA intake had a significantly reduced likelihood of having CKD compared with those in the lowest quartile of intake (multivariable-adjusted OR 0??69, 95??% CI 0??49, 0??99). ??-Linolenic acid intake was positively associated with CKD (OR, per standard deviation increase in ??-linolenic acid, 1??18, 95??% CI 1??05, 1??32). Total n-3 PUFA or total n-6 PUFA were not significantly associated with CKD. The highest compared with the lowest quartile of fish consumption was associated with a reduced likelihood of CKD (OR 0??68, 95??% CI 0??48, 0??97; P for trend??=??0??02). The present study shows that an increased dietary intake of long-chain n-3 PUFA and fish reduces the prevalence of CKD. Hence, a diet rich in n-3 PUFA and fish could have a role in maintaining healthy kidney function, in addition to roles of these nutrients in the prevention and modulation of other diseases.
%Z FOR Codes: 111101 110312


%0 Journal Article
%~ PubMed
%A Harris, Anthony
%A Cooper, Bruce A
%A Li, Jing Jing
%A Bulfone, Liliana
%A Branley, Pauline
%A Collins, John F
%A Craig, Jonathan C
%A Fraenkel, Margaret B
%A Johnson, David W
%A Kesselhut, Joan
%A Luxton, Grant
%A Pilmore, Andrew
%A Rosevear, Martin
%A Tiller, David J
%A Pollock, Carol A
%A Harris, David C
%T Cost-effectiveness of initiating dialysis early: a randomized controlled trial.
%B American Journal of Kidney Diseases
%D 2011
%C United States
%I W.B. Saunders Co.
%V 57
%N 5
%P 707-715
%@ 1523-6838
%X Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Tian, Xinrui
%A Liu, Zhuola
%A Niu, Bo
%A Zhang, Jianlin
%A Tan, Thian Kui
%A Lee, So Ra
%A Zhao, Ye
%A Harris, David C H
%A Zheng, Guoping
%T E-cadherin/&#946;-catenin complex and the epithelial barrier.
%B Journal of Biomedicine and Biotechnology
%D 2011
%C United States
%I Hindawi Publishing Corporation
%V 2011
%N 
%P 567305
%@ 1110-7251
%X E-Cadherin/?-catenin complex plays an important role in maintaining epithelial integrity and disrupting this complex affect not only the adhesive repertoire of a cell, but also the Wnt-signaling pathway. Aberrant expression of the complex is associated with a wide variety of human malignancies and disorders of fibrosis resulting from epithelial-mesenchymal transition. These associations provide insights into the complexity that is likely responsible for the fibrosis/tumor suppressive action of E-cadherin/?-catenin.
%Z FOR Codes: 601 110312


%0 Journal Article
%~ PubMed
%A Schwensen, Kristina G
%A Burgess, Jane S
%A Graf, Nicole S
%A Alexander, Stephen I
%A Harris, David C
%A Phillips, Jacqueline K
%A Rangan, Gopala K
%T Early Cyst Growth Is Associated with the Increased Nuclear Expression of Cyclin D1/Rb Protein in an Autosomal-Recessive Polycystic Kidney Disease Rat Model.
%B Nephron. Experimental nephrology
%D 2011
%C Switzerland, United
%I S. Karger AG
%V 117
%N 4
%P e93-103
%@ 1660-2129
%X In this study we hypothesised that proliferation, and the increased expression of G(1)-phase cyclins (D1, E) and phosphorylated retinoblastoma protein (p-Rb) is restricted to the early period of synchronized cyst growth in autosomal-recessive polycystic kidney disease (ARPKD).
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Cao, Qi
%A Wang, Changqi
%A Zheng, Dong
%A Wang, Ya
%A Lee, Vincent W S
%A Wang, Yuan Min
%A Zheng, Guoping
%A Tan, Thian Kui
%A Yu, Di
%A Alexander, Stephen I
%A Harris, David C H
%A Wang, Yiping
%T IL-25 Induces M2 Macrophages and Reduces Renal Injury in Proteinuric Kidney Disease.
%B Journal of the American Society of Nephrology : JASN
%D 2011
%C United States
%I Ovid
%V 22
%N 7
%P 1229-39
%@ 1533-3450
%X The kidney contains receptors for the cytokine IL-25, but the effects of IL-25 in CKD are unknown. Here, we induced adriamycin nephropathy in both BALB/c mice and severe combined immunodeficient (SCID) mice, and we injected IL-25 for 7 consecutive days starting at day 5 after adriamycin administration. BALB/c mice treated with IL-25 had less glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than control mice at day 28. IL-25 increased the levels of IL-4 and IL-13 in serum, kidney, renal draining lymph nodes, and CD4+ lymphocytes. IL-25 also directly suppressed effector macrophages in vitro and in vivo and induced alternatively activated (M2) macrophages in vivo. However, in SCID mice and in BALB/c mice treated with IL-4/13-neutralizing antibody, IL-25 failed to protect against renal injury and did not induce M2. In conclusion, IL-25 protects against renal injury in adriamycin nephropathy in mice by, at least in part, inducing Th2 immune responses.
%Z FOR Codes: 110704 110312


%0 Journal Article
%A Harris, David
%A Gopinath, Bamini
%A Mitchell, Paul
%T Is the link between chronic kidney disease and hearing loss in older patients likely to be causal?
%B Aging Health
%D 2011
%C United Kingdom
%I Future Medicine Ltd.
%V 7
%N 1
%P 5-7
%@ 1745-509X
%X 
%Z FOR Codes: 110315 110312 110308


%0 Journal Article
%~ PubMed
%A Cao, Q
%A Zheng, D
%A Wang, Y P
%A Harris, D C H
%T Macrophages and Dendritic Cells for Treating Kidney Disease.
%B Nephron Experimental Nephrology
%D 2011
%C Switzerland
%I S. Karger AG
%V 117
%N 3
%P e47-e52
%@ 1660-2129
%X Based on new understanding of the diverse biological functions of macrophages and dendritic cells (DC), the focus of studies on these cells has been expanded from their pathogenic role in renal diseases to include their potential to regulate inflammation and restore renal architecture and function. By exploiting their regulatory function, macrophages or DC have been used to treat experimental renal disease following their adoptive transfer. This review summarizes current progress in the therapeutic use of macrophages and DC in renal diseases. Key issues for ongoing research are discussed.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Wang, Yiping
%A Harris, David C H
%T Macrophages in renal disease.
%B Journal of the American Society of Nephrology
%D 2011
%C United States
%I Ovid
%V 22
%N 1
%P 21-27
%@ 1533-3450
%X Macrophages have heterogeneous phenotypes as they exercise their twofold role in the development and recovery of renal diseases. Some subpopulations of macrophages (M1) have a pathogenic function in renal inflammation, making them a logical target for elimination. Alternatively, M2 macrophage subpopulations resolve inflammation and repair injury, making them a potential therapeutic tool against renal injury. Here, we summarize recent findings regarding macrophage plasticity, and the various strategies for targeting or utilizing macrophages to treat renal disease. We highlight, in particular, the potential of renoprotective M2 macrophages to resolve inflammation and repair the kidney.
%Z FOR Codes: 110312


%0 Book Section
%A Lee, Vincent
%A Cao, Qi
%A Wang, Yiping
%A Harris, David
%T Role of Macrophages in Renal Injury,
Repair and Regeneration
%B Regenerative Nephrology
%D 2011
%C United Kingdom, Unit
%I Elsevier Inc.
%V 
%N 
%P 125-140
%@ 9780123809285
%E Goligorsky, Michael S.
%X 
%Z FOR Codes: 110312


%0 Book Section
%A Succar, Lena
%A Harris, David
%A Rangan, Gopala
%T Role of the Mammalian Target of Rapamycin (mTOR) Signalling Pathway in Podocytes in Glomerular Disease
%B An Update on Glomerulopathies – Etiology and Pathogenesis
%D 2011
%C Croatia
%I InTech
%V 
%N 
%P 183-202
%@ 9789533073880
%E Prabhakar, Sharma S.
%X 
%Z FOR Codes: 60111


%0 Journal Article
%~ PubMed
%A Sun, Yan
%A Yu, Hong
%A Zheng, Dong
%A Cao, Qi
%A Wang, Ya
%A Harris, David
%A Wang, Yiping
%T Sudan black B reduces autofluorescence in murine renal tissue.
%B Archives of Pathology & Laboratory Medicine
%D 2011
%C United States
%I College of American Pathologists
%V 135
%N 10
%P 1335-1342
%@ 1543-2165
%X Renal tissue emits intense autofluorescence, making it difficult to differentiate specific immunofluorescence signals and thus limiting its application to clinical biopsy material.
%Z FOR Codes: 110104


%0 Journal Article
%~ PubMed
%A Zheng, Dong
%A Wang, Yiping
%A Cao, Qi
%A Lee, Vincent W S
%A Zheng, Guoping
%A Sun, Yan
%A Tan, Thian K
%A Wang, Ya
%A Alexander, Stephen I
%A Harris, David C H
%T Transfused Macrophages Ameliorate Pancreatic and Renal Injury in Murine Diabetes Mellitus.
%B Nephron. Experimental nephrology
%D 2011
%C Switzerland
%I S. Karger AG
%V 118
%N 4
%P e87-99
%@ 1660-2129
%X Alternatively activated macrophages (M2 macrophages) are able to reduce renal injury in murine adriamycin nephropathy. However, the effect of M2 macrophages in other renal diseases such as diabetic nephropathy remains unknown.
%Z FOR Codes: 110704 110299


%0 Journal Article
%~ PubMed
%A Cooper, Bruce A
%A Branley, Pauline
%A Bulfone, Liliana
%A Collins, John F
%A Craig, Jonathan C
%A Fraenkel, Margaret B
%A Harris, Anthony
%A Johnson, David W
%A Kesselhut, Joan
%A Li, Jing Jing
%A Luxton, Grant
%A Pilmore, Andrew
%A Tiller, David J
%A Harris, David C
%A Pollock, Carol A
%A , the IDEAL Study
%T A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis.
%B The New England journal of medicine
%D 2010
%C United States
%I Massachusetts Medical Society
%V 363
%N 7
%P 609-19
%@ 1533-4406
%X In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease.
%Z FOR Codes: 110312


%0 Journal Article
%A Cooper, Bruce
%A Harris, David
%A Pollock, Carol
%T Author's Reply: Early versus Late Initiation of Dialysis
%B New England Journal Of Medicine
%D 2010
%C United States
%I Massachusetts Medical Society
%V 363:24
%N 
%P 2368-2370
%@ 0028-4793
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Cao, Qi
%A Wang, Yiping
%A Zheng, Dong
%A Sun, Yan
%A Wang, Ya
%A Lee, Vincent W S
%A Zheng, Guoping
%A Tan, Thian Kui
%A Ince, Jon
%A Alexander, Stephen I
%A Harris, David C H
%T IL-10/TGF-{beta}-Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis.
%B Journal of the American Society of Nephrology : JASN
%D 2010
%C United States
%I American Society of Nephrology
%V 21
%N 6
%P 933-42
%@ 1533-3450
%X IL-10/TGF-beta-modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF-beta (IL-10/TGF-beta Mu2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4+ T cell proliferation. IL-10/TGF-beta Mu2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4+CD25- T cells in vitro, and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-beta Mu2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-beta-modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease.
%Z FOR Codes: 110704


%0 Journal Article
%~ PubMed
%A Tan, Thian Kui
%A Zheng, Guoping
%A Hsu, Tzu-Ting
%A Wang, Ying
%A Lee, Vincent W S
%A Tian, Xinrui
%A Wang, Yiping
%A Cao, Qi
%A Wang, Ya
%A Harris, David C H
%T Macrophage Matrix Metalloproteinase-9 Mediates Epithelial-Mesenchymal Transition in Vitro in Murine Renal Tubular Cells.
%B The American journal of pathology
%D 2010
%C United States
%I American Society for Investigative Pathology
%V 176
%N 3
%P 1256-70
%@ 0002-9440
%X As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis.
%Z FOR Codes: 111699


%0 Journal Article
%~ PubMed
%A Phipps, Lisa M
%A Harris, David Ch
%T Review: Modelling the dialysate.
%B Nephrology
%D 2010
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 15
%N 4
%P 393-398
%@ 1440-1797
%X Dialysate prescription is evolving as new technology allows greater opportunity to alter dialysate constituents throughout dialysis, providing scope for tailored prescription for an individual patient. The intention of modelling or profiling is to improve the tolerability of dialysis and long-term patient outcomes. This approach can be applied to both electrolytes and water. Despite these advances in technology, benefits of modelling have not been demonstrated consistently. This review examines the use of individual prescription and modelling of dialysate sodium, ultrafiltrate, potassium, calcium, magnesium, bicarbonate and phosphate.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Vilayur, Eswari
%A Gopinath, Bamini
%A Harris, David C
%A Burlutsky, George
%A McMahon, Catherine M
%A Mitchell, Paul
%T The Association Between Reduced GFR and Hearing Loss: A Cross-sectional Population-Based Study.
%B American journal of kidney diseases : the official journal of the National Kidney Foundation
%D 2010
%C United States
%I WB Saunders Co.
%V 56
%N 4
%P 661-9
%@ 1523-6838
%X Chronic kidney disease (CKD) has long been associated with hearing loss in certain syndromes. Reported evidence to date has come from only small observational studies. We present the first community-based study to show an association between nonsyndromal CKD and hearing loss.
%Z FOR Codes: 110312 111706 110315


%0 Journal Article
%~ PubMed
%A Lee, Vincent W S
%A Qin, Xiaohong
%A Wang, Yiping
%A Zheng, Guoping
%A Wang, Ya
%A Wang, Ying
%A Ince, Jon
%A Tan, Thian K
%A Kairaitis, Lukas K
%A Alexander, Stephen I
%A Harris, David C H
%T The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis.
%B Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
%D 2010
%C United Kingdom, Belg
%I Oxford University Press
%V 25
%N 3
%P 717-30
%@ 1460-2385
%X Blockade of CD40-CD40 ligand (CD154) interactions protects against renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To investigate whether this protection relied on adaptive or cognate immunity, we tested the effect of CD40-CD154 blockade in severe combined immunodeficient (SCID) mice.
%Z FOR Codes: 110701 110707


%0 Journal Article
%~ PubMed
%A Harris, David C H
%A Chen, Yung-Ming
%A Saito, Akira
%A Yu, Alex W Y
%T Timely initiation of dialysis for chronic kidney disease: perspective from four Asian countries.
%B Nephrology
%D 2010
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 15 Suppl 2
%N 
%P 61-65
%@ 1440-1797
%X Recommendations about when to initiate dialysis for end-stage kidney failure have been made by a number of expert groups. These recommendations have led to changes in clinical practice, yet they are not based on high level evidence. In fact, most reported studies argue that dialysis should be started early rather than late, many are confounded and a number have reached the opposite conclusion. Probably more important than a prescribed level of renal function at which dialysis is initiated is the widespread adoption of a structured approach to pre-dialysis care and the recognition of the importance of pre-dialysis patient education. One of the main determinants of optimal initiation of dialysis is the time of referral of the patient to a nephrologist or a renal unit. In particular, early referral of patients with chronic kidney disease allows a planned initiation of dialysis, using from the start permanent vascular or peritoneal dialysis access.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Watson, Debbie
%A Zheng, Guoping
%A Wu, Huiling
%A Wang, Yuan Min
%A Wang, Yiping
%A Harris, David C H
%A Alexander, S I
%T CCL2 DNA vaccine to treat renal disease.
%B The international journal of biochemistry & cell biology
%D 2009
%C United Kingdom
%I Pergamon
%V 41
%N 0
%P 729-32
%@ 1357-2725
%X CCL2 DNA vaccines are directed against the host chemoattractant molecule CCL2 (MCP-1), a key chemokine in recruiting macrophages to sites of inflammation. Macrophages recruited by CCL2 lead to progressive renal injury. In rat models of disease unmodified CCL2 DNA vaccine in combination with a CCL5 (RANTES) DNA vaccine can protect against chronic renal disease. The mechanism of protection involves the induction of auto-antibodies to the CCL2. Introduction of the adjuvant p-tet into the DNA structure of the CCL2 vaccine leads to enhanced potency with the induction of specific Th1 cellular immunity. The strategies outlined here demonstrate a model for developing potent vaccines against highly restricted self targets.
%Z FOR Codes: 110101


%0 Journal Article
%~ PubMed
%A Prodjosudjadi, Wiguno
%A Suhardjono, Z
%A Suwitra, Ketut
%A Pranawa, Z
%A Widiana, I Gde Raka
%A Loekman, Jodi Sidharta
%A Nainggolan, Ginova
%A Prasanto, Heru
%A Wijayanti, Yanri
%A Dharmeizar, Z
%A Sja'bani, Mochammad
%A Nasution, M Yusuf
%A Basuki, Widodo
%A Aditiawardana, Z
%A Harris, David C H
%A Pugsley, David J
%A , Working Group of the Indonesian Society of Nephrology
%T Detection and prevention of chronic kidney disease in Indonesia: initial community screening.
%B Nephrology
%D 2009
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 14
%N 7
%P 669-674
%@ 1440-1797
%X AIM: This survey evaluated the prevalence of chronic kidney disease (CKD if estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m(2)) and its risk factors amongst subjects from urban and semi-urban areas. METHODS: History of hypertension, diabetes mellitus, kidney disease, cardio- and cerebrovascular diseases of subjects and their families was recorded. Blood pressure was determined as the mean of three readings in the sitting position and hypertension classified according to the Joint National Committee VII. Urinalysis was assessed using Combi 10R dipstick test. Random blood glucose and serum creatinine were measured in subjects with either hypertension, proteinuria, glycosuria and/or a history of diabetes. eGFR was calculated according Cockcroft-Gault (CG) adjusted by body surface area (BSA), Modification of Diet in Renal Disease (MDRD) and Chinese MDRD equations. RESULTS: Of 9412 subjects recruited, 64.1% were female. Persistent proteinuria was found in almost 3%. Systolic and diastolic hypertension was found in 10%, isolated systolic hypertension in 4.8% and isolated diastolic hypertension in 4.6%. CKD was found in 12.5% (CG), 8.6% (MDRD) or 7.5% (Chinese MDRD) of subjects with either hypertension, proteinuria and/or diabetes. Proteinuria, systolic blood pressure and a history of diabetes mellitus were independent predictors of impaired eGFR. Obesity and smoking history were found in 32.5% and 19.8%, respectively. CONCLUSION: The present study showed a high prevalence of CKD in representative urban and semi-urban areas and argues for screening and treatment of all Indonesians, particularly those at an increased risk of CKD.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Zheng, Guoping
%A Lyons, James Guy
%A Tan, Thian Kui
%A Wang, Yiping
%A Hsu, Tzu-Ting
%A Min, Danqing
%A Succar, Lena
%A Rangan, Gopala K
%A Hu, Min
%A Henderson, Beric R
%A Alexander, Stephen I
%A Harris, David C H
%T Disruption of E-Cadherin by Matrix Metalloproteinase Directly Mediates Epithelial-Mesenchymal Transition Downstream of Transforming Growth Factor-{beta}1 in Renal Tubular Epithelial Cells.
%B The American journal of pathology
%D 2009
%C United States
%I American Society for Investigative Pathology
%V 175
%N 2
%P 580-91
%@ 1525-2191
%X Epithelial-mesenchymal transition (EMT) plays an important role in organ fibrosis, including that of the kidney. Loss of E-cadherin expression is a hallmark of EMT; however, whether the loss of E-cadherin is a consequence or a cause of EMT remains unknown, especially in the renal system. In this study, we show that transforming growth factor (TGF)-beta1-induced EMT in renal tubular epithelial cells is dependent on proteolysis. Matrix metalloproteinase-mediated E-cadherin disruption led directly to tubular epithelial cell EMT via Slug. TGF-beta1 induced the proteolytic shedding of E-cadherin, which caused the nuclear translocation of beta-catenin, the transcriptional induction of Slug, and the repression of E-cadherin transcription in tubular epithelial cells. These findings reveal a direct role for E-cadherin and for matrix metalloproteinases in causing EMT downstream of TGF-beta1 in fibrotic disease. Specific inhibition rather than activation of matrix metalloproteinases may offer a novel approach for treatment of fibrotic disease.
%Z FOR Codes: 110316


%0 Journal Article
%~ PubMed
%A Vilayur, Eswari
%A Harris, David C H
%T Emerging therapies for chronic kidney disease: what is their role?
%B Nature Reviews. Neurology
%D 2009
%C United Kingdom
%I Nature Publishing Group
%V 5
%N 7
%P 375-383
%@ 1759-507X
%X The prevalence of chronic kidney disease (CKD) is increasing worldwide. The best therapies currently available focus on the control of blood pressure and optimization of renin-angiotensin-aldosterone system blockade. Currently available agents are only partially effective against hard end points such as the development of end-stage renal disease and are not discussed in this Review. Many other agents have been shown to reduce proteinuria and delay progression in animal models of CKD. Some of these agents, including tranilast, sulodexide, thiazolidinediones, pentoxifylline, and inhibitors of advanced glycation end-products and protein kinase C, have been tested to a limited extent in humans. A small number of randomized controlled human trials of these agents have used surrogate markers such as proteinuria as end points rather than hard end points such as end-stage renal disease or doubling of serum creatinine level. Emerging therapies that specifically target and reverse pathological hallmarks of CKD such as inflammation, fibrosis and atrophy are needed to reduce the burden of this chronic disease and its associated morbidity. This Review examines the evidence for emerging pharmacological strategies for slowing the progression of CKD.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Rangan, Gopala
%A Wang, Yiping
%A Harris, David
%T NF-kappaB signalling in chronic kidney disease.
%B Frontiers in Bioscience
%D 2009
%C United States
%I Frontiers in Bioscience
%V 14
%N 
%P 3496-3522
%@ 1093-4715
%X The mammalian NF-kappaB signalling pathway is an important intracellular transcription factor system that is induced in response to diverse extracellular stimuli. The hallmark of NF-kappaB activation is the nuclear translocation of dimeric Rel protein transcription factors, which regulate hundreds of kappaB-dependent genes that are involved in inflammation, immunity, apoptosis, cell proliferation and differentiation. In addition, cell-surface receptors (TNFR, Toll-like and angiotensin II, type 1 receptors), inhibitory kappaB kinases (IKK proteins), I kappaB proteins and factors regulating the post-translational modification of the Rel proteins (acetylation, phosphorylation), are other intracellular components that regulate NF-kappaB activation. Over the last decade, in vitro studies, animal models and human studies have provided evidence that upregulation of the canonical (RelA/p50) NF- kappaB isoform (in tubular epithelial cells, podocytes, mesangial cells, macrophages) has a pathogenic role in mediating chronic inflammation in chronic kidney disease (CKD). This review will examine current evidence regarding NF- kappaB isoforms and their potential role in the treatment of kidney failure due to CKD.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Tong, Allison
%A Sainsbury, Peter
%A Chadban, Steven
%A Walker, Rowan G
%A Harris, David C
%A Carter, Stacy M
%A Hall, Bronwyn
%A Hawley, Carmel
%A Craig, Jonathan C
%T Patients' experiences and perspectives of living with CKD.
%B American Journal of Kidney Diseases
%D 2009
%C United States
%I WB Saunders Co.
%V 53
%N 4
%P 689-700
%@ 0272-6386
%X Explicit incorporation of patients'' values and preferences is important in health care decision making. However, there are few data about this topic for patients with chronic kidney disease (CKD). We conducted 9 focus groups (3 each for CKD stages 1 to 5, CKD stage 5D, and CKD stages 1 to 5T). Five major themes were identified: (1) personal meaning of CKD, (2) managing and monitoring health, (3) lifestyle consequences, (4) family impact, and (5) informal support structures. Patients had to adjust to the disruptive and permanent implications of the illness on their physical health, identity, emotions, family, lifestyle, relationships, and employment. The overwhelming fatigue, complex treatment regimens, side effects, and liquid and diet restrictions constrained patients'' lives. Patients appreciated specialist care, but described the health care system as nonintegrated and believed they received insufficient information and psychosocial support. Choice of treatments was based on lifestyle, family impact, and physical comfort, seldom on clinical outcomes. Time was needed to comprehend the diagnosis, cope with uncertainty, integrate their treatment regimen into their daily routine, and reestablish a sense of normality in their lives. Rather than focusing on clinical targets, greater attention may need to be given to providing information and psychosocial and practical support at a patient-level not organ-specific level, to maximize patient quality of life.
%Z FOR Codes: 1117


%0 Journal Article
%~ PubMed
%A Tsukamoto, Yusuke
%A Wang, HaiYan
%A Becker, Gavin
%A Chen, Hung-Chun
%A Han, Dae-Suk
%A Harris, David
%A Imai, Enyu
%A Jha, Vivekanand
%A Li, Philip K T
%A Lee, Evan J C
%A Matsuo, Seiichi
%A Tomino, Yasuhiko
%A Tungsanga, Kriang
%A Yamagata, Kunihiro
%A Hishida, Akira
%T Report of the Asian Forum of Chronic Kidney Disease Initiative (AFCKDI) 2007. "Current status and perspective of CKD in Asia": diversity and specificity among Asian countries.
%B Clinical and Experimental Nephrology
%D 2009
%C Japan
%I Springer Japan KK
%V 13
%N 3
%P 249-256
%@ 1437-7799
%X The Japanese Society of Nephrology (JSN) sponsored the Asian Forum of CKD Initiative (AFCKDI) 2007 with the support of the International Society of Nephrology-Commission for Global Advancement in Nephrology (ISN-COMGAN), Asian Pacific Society of Nephrology (APSN), the Kidney Disease: Improving Global Outcome (KDIGO) and other national societies of nephrology in the Asian Pacific region on 27-28 May 2007 in Hamamatsu City, Japan. An international organising committee was established by leading experts of the CKD initiative. The main objective of this forum was to clarify the current status and perspectives of CKD and to promote coordination, collaboration and integration of initiatives in the Asian Pacific region. The forum received 56 papers from 16 countries; it began with the symposium "A Challenge to CKD in the world" and was followed by the ISN-COMGAN affiliated workshop "Current status and perspective of CKD in Asia". The second day was dedicated to discussion on the evaluation, surveillance and intervention in CKD in this area. At the end of the forum, we decided on the future plan as follows: (1) The AFCKDI will provide opportunities annually or biannually for every person who promotes CKD initiatives in the Asian Pacific region to join together and build consensus for action; (2) the second forum will be held in Kuala Lumpur on 4 May 2008 at the time of the 11th Asian Pacific Congress of Nephrology (APCN). Zaki Morad, President of the 11th APCN, will host the second forum; (3) the International Organising Committee (IOC) of the 1st AFCKDI will continue its function by adding other experts, including the organisers of the APCN; (4) the AFCKDI is not an organisation by itself, nor does it belong to any society, but is organised by each host national society of nephrology. The IOC will assist the domestic committee for the success of the forum and will assure the continuation of the mission; (5) in order to organise the forum and promote CKD initiatives in the Asia Pacific region, the AFCKDI will look for support by both national and international societies. The AFCKDI will keep an intimate and mutual relation with the ISN, APSN and KDIGO.
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Wang, Ying
%A Wang, Yiping
%A Cai, Qi
%A Zheng, Guoping
%A Lee, Vincent W S
%A Zheng, Dong
%A Li, Xiaomei
%A Tan, Thian Kui
%A Harris, David C H
%T By Homing to the Kidney, Activated Macrophages Potently Exacerbate Renal Injury.
%B The American journal of pathology
%D 2008
%C United States
%I Amer Soc Investigative Pathology
%V 172
%N 6
%P 1491-9
%@ 1525-2191
%X Macrophages are important mediators of injury in most types of human kidney diseases; however, the pathogenic importance of both macrophage number and activation status is unknown. To examine this question, severe-combined immunodeficient mice with adriamycin nephrosis, an experimental model of human focal segmental glomerulosclerosis, were treated intravenously with either resting (1 x 10(6) to 5 x 10(6)) or activated (1 x 10(3) to 1 x 10(6)) macrophages on day 6 postadriamycin administration, and the effects on kidney injury were examined. On day 28, renal injury was worse in the group that received activated macrophages at doses as low as 1 x 10(4) macrophages per mouse compared with control adriamycin nephrotic mice. However, treatment with resting macrophages at doses as high as 5 x 10(6) macrophages per mouse had no significant effect on either renal histology or function. The transferred activated macrophages homed to inflamed kidneys during the middle-to-late stages of the disease, but such homing was not observed for resting macrophages. This study of in vivo cell adoptive transfer supports the importance of macrophage activation status over macrophage number in causing renal injury. These data suggest that therapeutic strategies for treating progressive kidney diseases should target activated macrophages.
%Z FOR Codes: 110704 111601


%0 Book
%A Harris, David
%T Clinical Cases in Kidney Disease
%B 
%D 2008
%C Australia
%I McGraw-Hill
%V 
%N 
%P 
%@ 9780074717806
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ PubMed
%A Tong, Allison
%A Sainsbury, Peter
%A Carter, Stacy M
%A Hall, Bronwyn
%A Harris, David C
%A Walker, Rowan G
%A Hawley, Carmel M
%A Chadban, Steven
%A Craig, Jonathan C
%T Patients' priorities for health research: focus group study of patients with chronic kidney disease.
%B Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
%D 2008
%C United Kingdom
%I Oxford University Press
%V 23
%N 10
%P 3206-14
%@ 1460-2385
%X The inclusion of consumer preferences in prioritizing research topics is widely advocated, but prioritization is driven largely by professional agendas.
%Z FOR Codes: 111799 110312


%0 Journal Article
%~ PubMed
%A Blyth, Emily
%A Favaloro, Emmanuel J
%A Harris, David
%A Kairaitis, Lukas
%T Protein Z is reduced in chronic kidney disease and not elevated in patients on haemodialysis.
%B Blood Coagulation & Fibrinolysis
%D 2008
%C United States
%I Lippincott Williams and Wilkins
%V 19
%N 1
%P 23-25
%@ 0957-5235
%X Protein Z (PZ) is a vitamin K dependent serine protease inhibitor, which along with its cofactor Protein Z-dependant protease inhibitor (ZPI) has anti-Xa activity. PZ has previously been reported to be elevated in patients with end-stage chronic kidney disease (CKD) on haemodialysis but not in non-dialysed CKD patients raising the possibility that PZ may have a role in the bleeding diathesis of patients on haemodyalisis. PZ was measured in controls (n = 18), CKD on haemodialysis (n = 23) and CKD not on dialysis (n = 23). Patients on vitamin K antagonists, with acute inflammatory conditions (as measured by CRP) or liver dysfunction were excluded PZ levels were reduced in CKD patients when compared to levels in the control group (1.35 mug/mL vs 1.80 respectively, p = 0.022). Subgroup analysis revealed a trend toward reduction in mean PZ in the CKD subgroups (non-dialysed CKD group 1.37 (p = 0.08); haemodialysis 1.33 (p = 0.12)). There were no significant differences in the PZ levels for different stages of non-dialysed CKD patients when stratified by the level of glomerular filtration rate (GFR). These data show that PZ levels were reduced in patients with CKD, and not elevated in patients on haemodialysis, arguing against a role for PZ in the bleeding diathesis of renal failure. This finding is in contradiction to a previous report which found PZ to be elevated in patients on haemodialysis.
%Z FOR Codes: 1101 110312


%0 Journal Article
%~ PubMed
%A Wang, Yuan Min
%A Hu, Min
%A Wang, Ya
%A Polhill, Tania
%A Zhang, Geoff Yu
%A Wang, Yiping
%A Lee, Vincent W S
%A Harris, David C H
%A Alexander, Stephen I
%T Regulatory T cells in renal disease.
%B International Journal of Clinical and Experimental Medicine
%D 2008
%C United States
%I E-Century Publishing
%V 1
%N 4
%P 294-304
%@ 1940-5901
%X Regulatory T cells (Tregs) have a key role in immune homeostasis and in suppressing unwanted inflammatory responses toward self-antigens. Tregs have been implicated in the control of initial activation events, and play roles in limiting proliferation, differentiation and effector functions of T helper cells. However, the activities of Tregs in the development and progression of kidney disease are not fully elucidated. We have demonstrated the potency of Tregs in animal models of kidney disease. In this review, we summarise mechanistic information from rodent models on the roles of Tregs in glomerular immunopathology and discuss the function of Tregs in diverse kidney diseases. Further studies of Tregs should provide important insights into designing of therapeutic strategies to prevent human kidney disease.
%Z FOR Codes: 110704 110312 111601


%0 Journal Article
%~ PubMed
%A Lee, Vincent Weng Seng
%A Wang, Yuan Min
%A Wang, Yiping
%A Zheng, Dong
%A Polhill, Tania
%A Cao, Qi
%A Wu, Huiling
%A Alexander, Ian
%A Alexander, Stephen
%A Harris, David
%T Regulatory immune cells in kidney disease
%B American journal of physiology. Renal physiology
%D 2008
%C United States
%I American Physiological Society
%V 295
%N 2
%P F335-42
%@ 0363-6127
%X Lymphocytes and macrophages act as effector immune cells in the initiation and progression of renal injury. Recent data have shown that subpopulations of these immune cells (regulatory T lymphocytes and alternately-activated or regulatory macrophages) are potent modulators of tissue injury and repair in renal disease. Recent animal studies examining the therapeutic effect of these cells raise the exciting possibility that strategies targeting these cell types may be effective in treating and preventing kidney disease in humans. This review will describe their biological role in experimental kidney disease and therapeutic potential in clinical nephrology.
%Z FOR Codes: 110704


%0 Book
%A Harris, David
%T Clinical Cases in Kidney Disease
%B 
%D 2007
%C Australia
%I McGraw-Hill
%V 
%N 
%P 
%@ 9780074717806
%X 
%Z FOR Codes: 110312


%0 Journal Article
%~ Isi
%A Xu, JW
%A Hu, SL
%A Harris, D
%A Geng, LQ
%A Xu, XC
%A Zhang, AM
%A Li, Q
%A Sun, ZM
%A Zhai, ZM
%A Wang, YP
%A Liu, HL
%T Correlation of the CD4(+)CD25(high) T-regulatory cells in recipients and their corresponding donors to acute GVHD
%B TRANSPLANT INTERNATIONAL
%D 2007
%C United Kingdom
%I Blackwell Publishing Ltd
%V 20
%N 5
%P 440-446
%@ 0934-0874
%X 
%Z FOR Codes: 110323


%0 Journal Article
%~ PubMed
%A Zhai, Zhimin
%A Sun, Zimin
%A Li, Qing
%A Zhang, Aimei
%A Liu, Huilan
%A Xu, Jingwei
%A Xu, Xiucai
%A Geng, Liangquan
%A Harris, David
%A Hu, Shilian
%A Wang, Yiping
%T Correlation of the CD4+CD25high T-regulatory cells in recipients and their corresponding donors to acute GVHD.
%B Transplant international
%D 2007
%C United Kingdom
%I Wiley-Blackwell
%V 20
%N 5
%P 440-446
%@ 0934-0874
%X Graft-versus-host disease continues to be a major life-threatening complication after allogeneic hematopoietic stem cells transplantation (aHSCT). The relationship of acute GVHD (aGVHD) with the levels of peripheral CD4(+)CD25(high) T cells in patients after aHSCT and in their corresponding donors is not fully investigated. We examined the levels of CD4(+)CD25(high) T cells in patients after aHSCT and in their corresponding donors, and analyzed the relationship of CD4(+)CD25(high) T cells to the incidence and prognosis of aGVHD. The recipients with normal or high CD4(+)CD25(high) T cells (three of eight, 37.5%) had no or mild aGVHD (grade I), and all survived during the follow-up period. In striking contrast, the recipients with lower or no CD4(+)CD25(high) T cells suffered from greater than grade II aGVHD (four of four, 100%), and all died within 1-year post-aHSCT. Moreover, the number of CD4(+)CD25(high) T cells in recipients correlated significantly with that of their corresponding donors. The CD4(+)CD25(high) T cells from the recipients and their corresponding donors expressed high levels of Foxp3, and effectively suppressed the proliferation of CD4(+)CD25(-) responder T cells. This study suggests that human Treg cells may play an important role in aGVHD, as has been seen in murine models. The levels of peripheral CD4(+)CD25(high) T cells in recipients and donors could be helpful for predicting of the onset and outcome of aGVHD.
%Z FOR Codes: 110399


%0 Journal Article
%~ PubMed
%A Disney, Alex
%A Jersey, Peter D E
%A Kirkland, Geoff
%A Mantha, Murty
%A Charlesworth, John A
%A Gallagher, Martin
%A Harris, David
%A Gock, Hilton
%A Mangos, George J
%A Macmillan, Jamie
%A Liu, Wei
%A Viswalingam, Ajit
%T Darbepoetin alfa administered monthly maintains haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis: a multicentre, open-label, Australian study.
%B Nephrology (Carlton, Vic.)
%D 2007
%C Australia
%I Blackwell Publishing Asia
%V 12
%N 1
%P 95-101
%@ 1320-5358
%X AIM: Darbepoetin alfa, an erythropoiesis-stimulating protein, has a longer serum half-life than recombinant human erythropoietin, allowing less-frequent administration. This study aimed to demonstrate that once-monthly (QM) darbepoetin alfa administration would maintain haemoglobin (Hb) concentrations in subjects with chronic kidney disease (CKD) not receiving dialysis who had previously been administered darbepoetin alfa every 2 weeks (Q2W). METHODS: This was a multicentre study in which subjects with CKD receiving stable Q2W darbepoetin alfa doses and with stable Hb (100-130 g/L) were started on QM darbepoetin alfa dosing. The initial QM darbepoetin alfa dose was equivalent to the cumulative darbepoetin alfa dose administered during the month preceding enrollment. Darbepoetin alfa doses were titrated to maintain Hb concentrations between 100 and 130 g/L. The primary endpoint was the proportion of subjects maintaining mean Hb >or= 100 g/L during the evaluation period (weeks 21-33). RESULTS: Sixty-six subjects were enrolled in the study and all received at least one dose of darbepoetin alfa; 55 (83%) had mean Hb >or= 100 g/L during evaluation. Mean (SD) Hb concentrations at baseline and during the evaluation period were 119 (8.7) g/L and 114 (9.8) g/L, respectively. The median QM darbepoetin alfa dose at baseline and during the evaluation period was 80 microg. Darbepoetin alfa was considered to be well-tolerated. CONCLUSION: Patients with CKD not receiving dialysis who are receiving darbepoetin alfa Q2W can be safely and effectively extended to darbepoetin alfa QM. Dosing QM may simplify anaemia management for patients and health-care providers.
%Z FOR Codes: 110312 110312


%0 Journal Article
%~ PubMed
%A Wu, Huiling
%A Wang, Yuan Min
%A Wang, Yiping
%A Hu, Min
%A Zhang, Geoff Yu
%A Knight, John F
%A Harris, David C H
%A Alexander, Stephen I
%T Depletion of gammadelta T cells exacerbates murine adriamycin nephropathy.
%B Journal of the American Society of Nephrology : JASN
%D 2007
%C US
%I Lippincott Williams & Wilkins
%V 18
%N 4
%P 1180-1189
%@ 1046-6673
%X It has been reported that the presence of gammadelta T cells in kidney is associated with kidney damage in human IgA nephropathy and in rat models of chronic renal injury, including Adriamycin nephropathy (AN), but the functional role of gammadelta T cells in this setting is unknown. This study examined the functional role of gammadelta T cells in tissue injury in a murine model of AN. Murine AN was induced in BALB/c mice by a single injection of Adriamycin. gammadelta T cells as a proportion of CD3(+) T cells were significantly increased in AN kidneys (16.8 +/- 3.9%) but not in lymph nodes (1.3 +/- 0.8%; P < 0.001). The proportion of gammadelta T cells in AN kidney correlated positively with serum creatinine and glomerular sclerosis. The Vgammadelta T cell receptor (TCR) repertoire in kidney showed expansion of a subset of cells that expressed Vgamma6/Vdelta1 genes and that used canonical TCR Vgamma6/Vdelta1 sequences in the CDR3 region of the TCR. gammadelta T cells that were sorted from the kidneys expressed TGF-beta but not IL-4, IL-10, or IFN-gamma. gammadelta T cells also expressed the activating receptor NKG2D and the NKG2D adaptor molecule DAP12. RAE-1, a ligand of NKG2D, was upregulated in AN kidney. Depletion of gammadelta T cells using anti-TCR gammadelta antibody resulted in worsening of serum creatinine, glomerulosclerosis, and interstitial inflammation. These studies indicate the involvement of the gammadelta T cell in innate recognition and regulation of inflammation in AN.
%Z FOR Codes: 110704 110312


%0 Journal Article
%~ PubMed
%A Pollock, Carol A
%A Cooper, Bruce A
%A Harris, David C
%T Early start peritoneal dialysis.
%B Advances in chronic kidney disease
%D 2007
%C United States
%I WB Saunders Co.
%V 14
%N 3
%P e27-e34
%@ 1548-5595
%X The timing of commencement of dialysis is controversial, as it has an impact on the patient''s lifestyle, the dialysis capacity of renal services, and costs to both the individual and community. In patients with chronic kidney disease, the commencement of dialysis based on clinical features of uremia and laboratory indices that mandate dialysis therapy may not optimize outcomes. Currently reported studies are subject to potential confounding factors, including lead-time bias, the timing of referral, uniform predialysis care, patient age, comorbidity, and compliance. Despite the lack of supporting evidence, national and international expert panels have generally recommended adopting guidelines that support the initiation of dialysis at levels of kidney function that are higher than observed in current practice. No compelling evidence supports the initial use of one modality of dialysis over another, but initiation of peritoneal dialysis will likely preserve residual kidney function to a greater extent than will initiation of hemodialysis. As preservation of endogenous kidney function is an important goal in patients with end-stage kidney disease, this outcome may contribute to the choice of modality. Objective parameters that will guide the initiation of dialysis to maximize survival, reduce morbidity, and inform as to the economic benefit of implementing such practice will be available when the Initiating Dialysis Early and Late (IDEAL) study reports in 2009.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Wang, Y
%A Wang, Y P
%A Zheng, G
%A Lee, V W S
%A Ouyang, L
%A Chang, D H H
%A Mahajan, D
%A Coombs, J
%A Wang, Y M
%A Alexander, S I
%A Harris, D C H
%T Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal disease.
%B Kidney international
%D 2007
%C United States
%I Blackwell Publishing, Inc.
%V 72
%N 3
%P 290-9
%@ 1523-1755
%X Macrophage infiltration of the kidney is a prominent feature associated with the severity of renal injury and progressive renal failure. To determine the influence of macrophages in renal disease models in the absence of endogenous T and B cells, we performed adoptive transfer of macrophages into severe combined immunodeficient (SCID) mice. In this study, macrophages were isolated from the spleens of BALB/c mice and stimulated with lipopolysaccharide to induce classically activated M1 macrophages or with interleukin-4 (IL-4) and IL-13 to induce alternatively activated M2 macrophages. These macrophages were then infused into SCID mice with adriamycin nephropathy; an in vivo model of chronic inflammatory renal disease analogous to human focal segmental glomerulosclerosis. Mice infused with M1 macrophages had a more severe histological and functional injury, whereas M2 macrophage-induced transfused mice had reduced histological and functional injury. Both M1 and M2 macrophages localized preferentially to the area of injury and maintained their phenotypes even after 4 weeks. The protective effect of M2 macrophages was associated with reduced accumulation and possibly downregulated chemokine and inflammatory cytokine expression of the host infiltrating macrophages. Our findings demonstrate that macrophages not only act as effectors of immune injury but can be induced to provide protection against immune injury.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Veness, M J
%A Harris, D
%T Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers.
%B Australasian radiology
%D 2007
%C Australia
%I Blackwell Publishing Asia
%V 51
%N 1
%P 12-20
%@ 1440-1673
%X Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Li, Xiaomei
%A Li, Xiangpei
%A Qian, Long
%A Wang, Guosheng
%A Zhang, Hong
%A Wang, Xiaoqiu
%A Chen, Ke
%A Zhai, Zhimin
%A Li, Qing
%A Wang, Yiping
%A Harris, David C H
%T T regulatory cells are markedly diminished in diseased salivary glands of patients with primary Sjögren's syndrome.
%B The Journal of rheumatology
%D 2007
%C Canada
%I Journal of Rheumatology Publishing Co. Ltd.
%V 34
%N 12
%P 2438-2445
%@ 0315-162X
%X OBJECTIVE: To investigate the abnormalities of T regulatory cells (Treg) in salivary glands and peripheral blood in patients with primary Sjögren''s syndrome (pSS). METHODS: Levels of CD4+CD25+ high T cells of the peripheral blood of 52 patients with pSS were measured by flow-cytometric assay. Lower lip salivary gland biopsies were examined by immunohistochemistry, using monoclonal mouse anti-human antibodies [CD25, CD4, CD8, CD68, forkhead transcription factor (Foxp3)] in 30 patients with pSS. Using real-time polymerase chain reaction, Foxp3 messenger RNA expression was assessed in the salivary glands and CD4+ T cells from peripheral blood. RESULTS: Many inflammatory cells, predominantly CD4+ and CD8+ T cells and macrophages, were found in salivary glands of patients with SS, but CD4+CD25+ Treg numbers and Foxp3 expression were markedly reduced in those biopsy samples. Levels of CD4+CD25+ high T cells and Foxp3 expression in peripheral blood of patients with pSS were significantly lower than in healthy controls. However, the inhibitory function of CD4+CD25+ T cells in pSS was unchanged compared to that of controls. Peripheral CD4+CD25+ high T cell numbers in pSS did not correlate with Schirmer''s test and salivary flow rate, or with the presence or absence of anti-SSA/SSB antibodies and immunoglobulin level. CONCLUSION: The remarkable reduction of Treg numbers in salivary glands and reduction of CD4+CD25+ high T cells in peripheral blood suggests a possible role for absence of Treg in the pathogenesis of salivary gland destruction in pSS.
%Z FOR Codes: 110322