Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation.
BACKGROUND
The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation.


METHODS
Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention. In another 115 patients with diastolic or systolic CHF, we investigated a possible relationship between zonulin and CHF severity.


RESULTS
In the AICD cohort, zonulin associated inversely with serum creatinine (p = 0.013), carboxymethyl-lysine calprotectin (p < 0.001), and kynurenine (p = 0.009) and positively with homoarginine (p < 0.001). In the subgroup with type-2 diabetes (T2D) (n = 51), zonulin increased significantly with high-sensitivity CRP (p = 0.014). In the CHF cohort, we found a highly significant rise of NT-proBNP, but not of zonulin with NYHA functional classes I-IV or other parameters of CHF severity.


CONCLUSIONS
The inverse associations of zonulin with creatinine and markers of cardio-vascular risk (high CMLcalprotectin and kynurenine, low homoarginine) are novel findings that need further experimental and clinical clarification. Our study indicates zonulin involvement in metabolic inflammation in T2D, but no association with disease status in CHF.
Thomas B
TB
Dschietzig
Felix
F
Boschann
Jana
J
Ruppert
Franz P
FP
Armbruster
Andreas
A
Meinitzer
Dragic
D
Bankovic
Veselin
V
Mitrovic
Christoph
C
Melzer
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002772:Cholera Toxin / Q000097:blood*; D005260:Female; D006242:Haptoglobins; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000175:diagnosis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors; D012720:Severity of Illness Index
D015415:Biomarkers; D006242:Haptoglobins; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin