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The CD40‐CD40L costimulatory pathway is critical for T cell activation in autoimmune disease. We have previously found that blocking the CD40‐CD40L pathway using a dendritic cell‐targeted CD40 DNA (DEC‐CD40) vaccine prevented the development of Heymann nephritis. In this study, we explored the effect of a DEC‐CD40 vaccine in the treatment of experimental autoimmune glomerulonephritis (EAG), an animal model of human Goodpasture's disease induced by antigen α3IV‐NC1. DEC‐CD40 vaccine given at week 3 and week 6 after 3IV‐NC1 injection reduced kidney structural and functional injury significantly in EAG. DEC‐CD40 vaccination suppressed Th17 cell numbers and Th17 immune responses in kidney and spleen, but did not alter Th1 cells number and responses. Serum derived from rats with DEC‐CD40 vaccination suppressed Th17 differentiation, but not Th1 differentiation in vitro. Furthermore, B cell activation, driven by Th17 cytokines, was suppressed by serum from rats vaccinated with DEC‐CD40. A DNA vaccine encoding CD40 and targeting dendritic cell, ameliorates kidney injury in both early and late stages in EAG rats, indicating DEC‐CD40 vaccination has a therapeutic role in EAG. Its effect is associated with the reduction of Th17 differentiation and Th17‐mediated B cell activation. DEC‐CD40 vaccination has a therapeutic role in experimental autoimmune glomerulonephritis, which is associated with the reduction of Th17 differentiation and Th17‐mediated B cell activation. [ABSTRACT FROM AUTHOR]

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 (h CD39 Tg) 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 h CD39 Tg and WT mice. h CD39 Tg mice were protected from renal injury in AN with decreased urinary protein and serum creatinine, and significantly less renal injury compared with WT mice. While WT CD25+ and h CD39 Tg CD25− T cells conferred some protection against AN, h CD39 Tg CD25+ Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, h CD39 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. [ABSTRACT FROM AUTHOR]

AFCKDI RECOMMENDATIONS FOR EARLY DETECTION OF CHRONIC KIDNEY DISEASE 1. Targets Patients with diabetes, hypertension Those with family history of chronic kidney disease (CKD) Individuals receiving potentially nephrotoxic drugs, herbs or substances or taking indigenous medicine Patients with past history of acute kidney injury Individuals older than 65 years 2. Tools Spot urine sample for protein with standard urine Dipstick test (need a repeat confirmatory test if positive) Dipstick for red blood cells (need confirmation by urine microscopy) An estimate of glomerular filtration rate based on serum creatinine concentration 3. Frequency of screening Screening frequency for targeted individuals should be yearly if no abnormality is detected on initial evaluation. 4. Who should perform the screening Doctors, nurses, paramedical staff and other trained healthcare professionals 5. Intervention after screening Patients detected to have CKD should be referred to primary care physicians with experience in management of kidney disease for follow up. A management protocol should be provided to the primary care physicians. Further referral to nephrologists for management will be based on the protocol together with clinical judgment of the primary care physicians with their assessment of the severity of CKD and the likelihood of progression. 6. Screening for cardiovascular disease risk It is recommended that cardiovascular disease risk factors should be screened in all patients with CKD. [ABSTRACT FROM AUTHOR]

Background. 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. [ABSTRACT FROM PUBLISHER]

In a previous study we found that an episode of acute subclinical nephrotoxicity with gentamicin (G) (but not that induced by another proximal tubular cell nephrotoxin: ferric nitrilotriacetate, FeNTA), paradoxically reduced the progression of renal function and injury in uninephrectomized rats with nephrotic glomerular disease due to Adriamycin nephropathy (AN). Here, we hypothesized that subclinical exposure to G reduces early renal cortical tubulointerstitial inflammation and NF-κB activation in AN. To test this hypothesis, male Wistar rats with established AN received either G (10, 40, or 80 mg/kg by daily s.c.i. for 3 days), FeNTA (1.25, 5, or 10 mg/kg by a single i.p.i.), or vehicle (n = 8 per group), 13 to 15 days after disease induction. Although G and FeNTA caused acute tubular necrosis in a dose-dependant manner (day 17), only the highest doses (10 mg/kg and 80 mg/kg) produced an acute elevation in the serum creatinine. On day 33, chronic tubulointerstitial inflammation (tubular atrophy, interstitial ED-1 + /CD8 + cell accumulation) and NF-κB activation were exacerbated only in the groups that caused functional nephrotoxicity. These data suggest that: 1) the protective effect of subclinical G nephrotoxicity in chronic AN does not involve early changes in interstitial inflammation or NF-κB activation; and 2) a single episode of G exposure must be accompanied by clinically apparent nephrotoxicity in order to accelerate progression in a nonuremic model of chronic glomerular disease. [ABSTRACT FROM AUTHOR]

Background/Aim: Inhibition of nuclear factor κB with the antioxidant pyrrolidine dithiocarbamate (PDTC) reduced tubulointerstitial injury in Adriamycin nephropathy (AN), whereas N-acetylcysteine (NAC) was ineffective. Here we hypothesize that PDTC reduces the renal cortical expression of nuclear factor κB dependent cytokines in AN. Methods: Male Wistar rats received a single intravenous injection of doxorubicin hydrochloride (7.5 mg/kg). NAC (150 mg/kg twice daily i.p.), PDTC (50 mg/kg twice daily i.p.), or vehicle were commenced on day 14 and continued until day 30. Results: On day 30, mRNAs of selected cytokines were increased in AN (TNF-α 3.4-fold, MCP-1 5.1-fold, IL-10 2.7-fold, TGF-β1 3.5-fold, all p < 0.05) as determined by RT-PCR. PDTC reduced IL-10 and TGF-β1 mRNAs (p < 0.05), whereas the upregulation of MCP-1 and TNF-α mRNAs was not affected. In contrast, NAC increased TNF-α and IL-10 mRNAs (p < 0.05). Nuclear protein levels of activator protein-1 were increased in AN (4.4-fold, p < 0.01) and not significantly altered by PDTC (3.0-fold, p = 0.13) or NAC (5.2-fold, p = 0.18). Conclusions: The protective effects of PDTC in AN are not associated with a local reduction in TNF-α and MCP-1 gene expression. The latter may be due to continued transactivation by activator protein-1. These data also suggest that IL-10 and TGF-β1 mRNA expressions are PDTC dependent and have a role in mediating tubulointerstitial injury.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents the abstract 'Partial Depletion of Macrophages By ED7 Reduces Renal Injury in Adriamycin Nephropathy,' by Yiping Wang, Yuet-Ching Tay, Tim Spicer, Lucas Kairaitis, Yang Wang, Ling Zheng and David C.H. Harris.

Presents the abstract 'Blockade of CD40-CD50 Ligand Reduced Renal Injury in Chronic Proteinuric Renal Disease,' by Yiping Wang, Lukas Kairaitis, Yuet-Ching Tay, Yang Wang, Ling Zheng and David C.H. Harris.

Presents the abstract 'Reconstitution of CD4+ T Cells Reduces Renal Injury in Scid Mice With Adriamycin Nephropathy,' by Yiping Wang, Lukas Kairaitis, Yuet-Ching Tay, Yang Wang, Ling Zheng and David C.H. Harris.