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Minimal change disease: a dysregulation of the podocyte CD80–CTLA-4 axis?

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Abstract

Background

Minimal Change Disease (MCD) is associated with CD80 expression in podocytes and elevated urinary CD80 excretion during active renal disease. We have evaluated the urinary excretion of CTLA-4 and CD80 during different stages of the nephrotic syndrome in patients with MCD to test the hypothesis that persistent increased urinary CD80 excretion in patients with MCD in relapse is due to an ineffectual CTLA-4 response of the host to curtail the activation of CD80.

Methods

Thirty-two children with biopsy-proven MCD were studied during relapse and/or remission. Eleven healthy subjects served as controls.

Results

Urinary CD80 excretion was significantly increased in MCD patients in relapse relative to that in MCD patients in remission (p < 0.001) and controls (p < 0.001). Although urinary CTLA-4 excretion was higher in MCD patients in relapse than in MCD patients in remission (p = 0.01) and controls (p = 0.03), no significant correlation was observed between urinary CD80 excretion and urinary CTLA-4 level in MCD patients at the time of relapse (p = 0.06). At the time of remission, CD80 had decreased significantly in all patients, but CTLA-4 levels either decreased or remained unchanged in all but five patients, and no correlation was observed between urinary CD80 excretion and CTLA-4 level (p = 0.7).

Conclusions

Urinary CTLA-4 levels do not correlate with urinary CD80 excretion, suggesting the possibility that the CTLA4 response may be suboptimal in this disease during relapse.

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Acknowledgments

This study was supported by NIH R01DK080764 to E.H.G. and R.J.J.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, 1600 SW Archer Rd., HD214, Gainesville, FL, 32610, USA

    Gabriel Cara-Fuentes, Heiman Wang & Eduardo H. Garin

  2. Department of Pathology, University of Florida, Gainesville, FL, USA

    Clive H. Wasserfall

  3. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO, USA

    Richard J. Johnson

Authors
  1. Gabriel Cara-Fuentes
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  2. Clive H. Wasserfall
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  3. Heiman Wang
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  4. Richard J. Johnson
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  5. Eduardo H. Garin
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Corresponding author

Correspondence to Eduardo H. Garin.

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Cara-Fuentes, G., Wasserfall, C.H., Wang, H. et al. Minimal change disease: a dysregulation of the podocyte CD80–CTLA-4 axis?. Pediatr Nephrol 29, 2333–2340 (2014). https://doi.org/10.1007/s00467-014-2874-8

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  • DOI: https://doi.org/10.1007/s00467-014-2874-8

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