Plasma Zonulin Levels in Childhood Nephrotic Syndrome

Abstract

Objective: We conducted this study to test the hypothesis that plasma zonulin levels are elevated in pediatric patients with nephrotic syndrome compared to healthy controls. Study Design: Plasma zonulin levels were measured by ELISA in 114 children enrolled in the NEPTUNE study. Clinical and laboratory data were retrieved from the NEPTUNE database. Results: The median age of the patients was 10 (IQR = 5 to 14) years, 59 were male, 64 had minimal change disease, 47 focal segmental glomerulosclerosis, median eGFR was 96 (IQR = 80 to 114) ml/min/1.73 m 2 , and median urine protein:creatinine ratio was 0.5 (IQR = 0.1 to 3.4) (g:g). The plasma zonulin level was 14.2 ± 5.0 vs. 10.2 ± 2.5 ng/ml in healthy adults in a report using the same assay kit, P = 0.0025. These findings were confirmed in an independent cohort of children with nephrotic syndrome compared to healthy age-matched controls, P = 0.01. Zonulin concentrations did not differ in children with minimal change disease vs. focal segmental glomerulosclerosis, frequently relapsing vs. steroid-dependent vs. steroid-resistant clinical course, and were not influenced by the immunosuppressive treatment regimen. There was no relationship between plasma zonulin levels and the absolute or percentage change in proteinuria from enrollment until the time of the zonulin assay. Conclusion: Plasma zonulin levels are elevated in childhood nephrotic syndrome regardless of level of proteinuria or specific treatment. The cause of the high plasma zonulin levels and whether zonulin contributes to glomerular injury requires further study.

Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study

“…Zonulin secretion is increased in gluten-sensitive patients and it could play a role in the pathophysiology of SRNS through a direct effect on podocytes ( 22 ) or indirectly by enhancing gut permeability to potentially toxic (or immunogenic) proteins produced by the microbiota ( 17 , 21 , 22 ). Indeed, recent data demonstrated that zonulin levels were increased in children with INS ( 58 ) and we observed in our study that two children that experienced complete remission after GF/DF implementation had higher zonulin levels before the intervention and the level decreased at week 4. Although the exact mechanisms responsible for the proteinuria remain uncertain, one hypothesis is that exposure to sensitive antigens may trigger inflammatory mediators that could systemically lead to podocyte injury ( 14 ).…”

Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review

“…Meanwhile, Zonulin may perturb the actin cytoskeleton and cell–cell junctions in the gut epithelium by activating epidermal growth factor receptor (EGFR) through protease-activated receptor 2 (PAR2), and GPCR2 [ 71 ]. Increased plasma Zonulin was associated with nephrotic syndrome in children regardless of the quantity of proteinuria or therapeutic regimen [ 72 ]. However, one of the included studies showed that Zonulin was not elevated in patients with CKD [ 23 ].…”

Interleukin‐10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study

“…Pediatric studies examining zonulin levels have not included critically ill patients and have focused on patients with chronic inflammatory conditions. [28][29][30] In addition to differences in the study population, our study examined zonulin at 2 time points, allowing for an assessment of zonulin under 2 conditions for the same patient, and found a decrease in zonulin postoperatively. Downregulation of zonulin has been reported and found to be associated with beneficial physiologic changes to the epithelial barrier.…”

“…Both studies examined zonulin only at 1 time point. Pediatric studies examining zonulin levels have not included critically ill patients and have focused on patients with chronic inflammatory conditions 28‐30 . In addition to differences in the study population, our study examined zonulin at 2 time points, allowing for an assessment of zonulin under 2 conditions for the same patient, and found a decrease in zonulin postoperatively.…”