Abstract: FR-OR021

Plasma Zonulin Levels in Childhood Nephrotic Syndrome (NS)

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Trachtman, Howard, NYU Langone Med Ctr, New York City, New York, United States
  • Gipson, Debbie S., University of Michigan, Ann Arbor, Michigan, United States
  • Lemley, Kevin V., Children's Hospital Los Angeles, Los Angeles, California, United States
  • Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States
  • Faul, Christian, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Morrison, Debra J., NYU Medical Center, New York, New York, United States
  • Vento, Suzanne M., NYU Langone Medical Center, New York, New York, United States
  • Goldberg, Judith D,, New York University School of Medicine, New York, New York, United States
  • Ahn, Dong-hyun, New York University School of Medicine, New York, New York, United States
Background

Case reports suggest that NS is responsive to dietary modifications including a gluten-free diet (GFD). In celiac disease, zonulin is released from enterocytes after exposure to gliadin, activates protease activated receptor 2 (PAR2), and perturbs the actin cytoskeleton and cell-cell junctions in the gut. PAR2 is present on podocytes and, therefore, zonulin may increase glomerular permeability in NS. We conducted this study to test the hypothesis that plasma zonulin levels are elevated in pediatric patients with NS.

Methods

Plasma specimens collected from patients ≤18 yr old with minimal change disease or FSGS enrolled in the NEPTUNE study, were tested. Clinical and laboratory data were retrieved coincident with the visit when the zonulin level was measured. Samples were available for testing from the 4 or 8 month visit. Plasma zonulin levels were measured by ELISA. Results (mean±SD or median (IQR)) were analyzed by t-test, Wilcoxon, Kruskal-Wallis, or linear regression and considered significant if P<0.05

Results

There were 113 patients, 9.5±4.9 yr, 53% male,42% white, 40% black and 18% other. Disease classification was infrequent relapser in 27%, frequent relapser/steroid dependent 42% and steroid resistant 30%. The mean BP, eGFR, and serum albumin were normal. Urine protein:creatinine (UPC) ratio was 3.9±6.9 (g:g). The plasma zonulin level in NS children was 14.2±6.0 vs 10±2.5 ng/ml in healthy adults ( P<0.01) and was >3 standard deviations above the mean in 27%. There was a trend toward lower zonulin levels in children with UPC ≥2 vs <2, 12.9(7.4) vs 16.7(8.0) (P=0.051). Plasma zonulin levels did not differ by eGFR, disease classification, or BP. Plasma zonulin and serum albumin concentrations were directly correlated, r=0.24, P=0.04.

Conclusion

The plasma zonulin level was significantly elevated in more than a quarter of children with NS and was unrelated to BP or eGFR. We observed a significant relationship between zonulin values and serum albumin but not proteinuria. There was a trend to lower zonulin levels in children with nephrotic-range proteinuria. Further study is needed to determine the relationship between plasma zonulin levels and proteinuria and to test whether the plasma zonulin level can be used to predict response to a GFD in children with NS.

Funding

  • NIDDK Support