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Abstract: SA-PO454

Expression and Functional Activity of Multidrug Resistance-Associated Protein-1 and P-Glycoprotein on T-Cells Is Associated with Steroid Resistance Nephrotic Syndrome in Children

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Prasad, Narayan, SGPGIMS CAMPUS, Lucknow, India
  • Singh, Harshit, SGPGIMS, Lucknow , India
  • Chaturvedi, Saurabh, SGPGIMS, Lucknow , India
  • Jaiswal, Akhilesh, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
  • Agarwal, Vikas, SGPGIMS, Lucknow , India
Background

Steroid remains as mainstay of therapy for Idiopathic Nephrotic Syndrome (NS). Other than histological factors like changes from minimal change to FSGS, pharmacogenomic factors may affect steroid response,however not well studied. Overexpression of P-glycoprotein (P-gp) and Multidrug resistance associated protein 1 (MRP-1) modulate pharmacokinetics of steroid and contribute in steroid resistance.

Methods

P-gp, MRP-1 expression were evaluated on whole blood and functional activity on peripheral blood mononuclear cells (PBMCs) by Flow Cytometry in steroid sensitive NS (SSNS) (n=80,male 43, age=8.54±4.3 yrs);and steroid resistant NS (SRNS) (n=50, male 29, age=7.72±3.6yrs). Multi resistance activity factor (MAF) was calculated using formula (MAFMDR1=100× (FMDR1-F0)/FMDR1).

Results

Percentage of P-gp (10.35±2.15 vs 4.19±1.07, p<0.001);and MRP-1(17.03±3.45 vs 8.71±2.97, p<0.001) were significantly higher in SRNS than SSNS. Absolute P-gp (64.96±12.78 vs 32.63±12.07, p<0.001) and MRP-1 (64.72±10.27 vs 40.28±11.24, p<0.001) expression were also significantly high in SRNS. P-gp expression on CD4+ (6.08±1.06 vs 4.34±1.47, p<0.001); and CD8+cells (8.65±2.19 vs 3.99±1.72, p<0.001) was significantly higher in SRNS than SSNS. MRP-1 expression on CD4+ cells (12.06±2.91 vs 3.35±0.83, p=0.001); and CD8+cells (5.11±0.68 vs 1.59±0.39, p<0.001) was significantly high in SRNS.Functional activity of P-gp (66.12±12.71 v/s 28.22±7.35, p<0.001);and MRP-1 (72.30±8.38 v/s 32.38±8.89,p<0.001) was significantly increased in SRNS.

Conclusion

Overexpression of P-gp and MRP-1 on T cells contribute in steroid resistance and may be biomarker of steroid resistance.Use of P-gp and MRP-1 inhibitors may prevent SRNS status.

Funding

  • Government Support - Non-U.S.