ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO816

Can Multidrug Resistance-Associated Protein-1 and P-Glycoprotein Expression on Peripheral Blood Lymphocytes Be Used as Biomarkers to Predict Steroid Resistance in Idiopathic Nephrotic Syndrome?

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Prasad, Narayan, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  • Singh, Harshit, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  • Jaiswal, Akhilesh, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  • Chaturvedi, Saurabh, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
  • Agarwal, Vikas, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Background

Steroid remains mainstay therapy for Idiopathic Nephrotic Syndrome (INS). Other than histological changes, pharmacogenomic factors may also affect steroid response. Overexpression of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance.

Methods

P-gp, and MRP-1 expression were evaluated on whole blood and functional activity on PBMCs in steroid-sensitive nephrotic syndrome (SSNS) (n=170, M=103, age=8.54±4.3 yrs); steroid-resistant nephrotic syndrome (SRNS) (n=81, M=43, age=7.43±4.6 yrs) patients. The genetic variants G2677T/A of MDR-1 gene were genotyped by PCR-RFLP technique.

Results

Biochemical difference were found in 24hrs urinary protein/Creatinine ratio (SSNS=0.13±.0.06, SRNS=3.67±0.91, p<0.001), total cholesterol (SSNS=144.21±34.61, SRNS=460.52±201.09, p<0.001).
Percentage expression of P-gp (9.80±3.44 and 4.36±2.05, p<0.001); and MRP-1 (13.46+4.80 and 7.75+3.22, p<0.001) was significantly higher in SRNS than SSNS. P-gp expression on CD4+ (6.08±2.06 v/s 4.34±1.97, p=0.008); and CD8+cells (8.65±2.19 v/s 3.99±1.72, p<0.001) was high in SRNS than SSNS respectively. MRP-1 expression on CD4+ and CD8+cells was higher in SRNS (12.06±2.91 v/s 3.35±1.83, p=0.043); (5.11±2.68 v/s 1.59±0.99, p<0.001) respectively. Functional activity of P-gp and MRP-1 was significantly increased in SRNS as compared to SSNS (66.26±+15.77 and 30. 82±9.87, p<0.001); (67.62+14.67 and 32.97+11.36, p<0.001) respectively. ROC curve predictive cut-off values percentage of P-gp (7.13%) and MRP-1 (9.62%) was found to be predictive of steroid resistance with a sensitivity of 90% and 80.7%, and specificity of 90% and 80%, respectively. Moreover, homozygous mutant allele TT+AA was significantly associated with a resistant population of nephrotic syndrome (p=0.025, OR = 2.86 CI=1.14-7.14). The expression of P-gp (9.68±4.99 v/s 5.88±3.38, p=0.002) was significantly higher in the patients of homozygous mutant alleles compared to wildtype GG.

Conclusion

Overexpression of P-gp and MRP-1 on peripheral blood lymphocytes may be used as biomarkers for SRNS with high sensitivity and specificity. Use of P-gp and MRP-1inhibitors may prevent steroid resistance.