PMID- 34170951
OWN - NLM
STAT- MEDLINE
DCOM- 20211117
LR  - 20211117
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 6
DP  - 2021
TI  - Could serum zonulin be an intestinal permeability marker in diabetes kidney 
      disease?
PG  - e0253501
LID - 10.1371/journal.pone.0253501 [doi]
LID - e0253501
AB  - Zonulin is a protein associated with the tight junction complex opening at the 
      intestinal epithelium, previously linked to obesity, cardiovascular diseases, 
      type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, its 
      role in CKD has not been totally elucidated. This study aimed to evaluate zonulin 
      levels in subjects with diabetic kidney disease (DKD). This case-control study 
      included two cases groups: 1) Advanced DKD cases: T2DM patients with estimated 
      glomerular filtration rate (eGFR) <60ml/min/1.73m2; 2) Albuminuric T2DM cases: 
      diabetic patients with urinary albumin excretion (UAE) >30mg/g creatinine, but 
      with eGFR>60ml/min/1.73m2. Two control groups were also included: 1) T2DM 
      controls: patients with T2DM without impaired kidney function; 2) Non-T2DM 
      controls: subjects without T2DM and normal renal function. Serum levels of 
      zonulin were measured by ELISA. Eighty-six individuals were included. Zonulin 
      levels was different among study groups (P = 0.003). T2DM controls presented 
      higher zonulin levels than non-T2DM controls [(131.35 (83.0-170.5) vs. 87.25 
      (54.7-111.8), P = 0.018] and advanced DKD cases [63.72 (45.03-106.0); P = 0.007]. 
      Zonulin showed a positive correlation with eGFR (r = 0.222; P = 0.040), total 
      cholesterol (r = 0.299; P = 0.034), LDL (r = 0.258; P = 0.021), and negative with 
      albuminuria (r = -0.243; P = 0.024) and body fat (r = -0.271; P = 0.014). In the 
      multivariate logistic regression analyses, zonulin levels were independently 
      associated to renal outcomes [OR 0.99 (0.98-0.99, P = 0.012)] after 5-year 
      inclusion. In conclusion, increased zonulin levels in patients with TD2M without 
      renal disease suggest an impaired intestinal permeability. Moreover, its 
      association with renal outcomes could indicate its use as a disease monitoring 
      marker. However, the mechanisms behind this association should be better 
      understood.
FAU - Carpes, Larissa Salomoni
AU  - Carpes LS
AUID- ORCID: 0000-0002-0818-5383
AD  - Faculty of Medicine, Post Graduate Program in Food, Nutrition and Health, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
FAU - Nicoletto, Bruna Bellincanta
AU  - Nicoletto BB
AD  - Life Sciences Knowledge Area, Universidade de Caxias do Sul, Caxias do Sul, Rio 
      Grande do Sul, Brazil.
FAU - Canani, Luis Henrique
AU  - Canani LH
AD  - Faculty of Medicine, Post Graduate Program in Medical Sciences: Endocrinology, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
AD  - Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
FAU - Rheinhemer, Jakeline
AU  - Rheinhemer J
AD  - Faculty of Medicine, Post Graduate Program in Medical Sciences: Endocrinology, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
FAU - Crispim, Daisy
AU  - Crispim D
AD  - Faculty of Medicine, Post Graduate Program in Medical Sciences: Endocrinology, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
AD  - Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
FAU - Souza, Gabriela Correa
AU  - Souza GC
AD  - Faculty of Medicine, Post Graduate Program in Food, Nutrition and Health, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
AD  - Food and Nutrition Research Center, Hospital de Clinicas de Porto Alegre, 
      Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210625
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Haptoglobins)
RN  - 0 (Protein Precursors)
RN  - 0 (zonulin)
SB  - IM
MH  - Aged
MH  - Biomarkers/blood
MH  - Diabetes Mellitus, Type 2/*blood
MH  - Diabetic Nephropathies/*blood
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Haptoglobins
MH  - Humans
MH  - Intestinal Mucosa/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Permeability
MH  - Protein Precursors/*blood
MH  - Renal Insufficiency, Chronic/*blood
MH  - Retrospective Studies
PMC - PMC8232531
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/06/26 06:00
MHDA- 2021/11/18 06:00
PMCR- 2021/06/25
CRDT- 2021/06/25 17:19
PHST- 2021/01/07 00:00 [received]
PHST- 2021/06/06 00:00 [accepted]
PHST- 2021/06/25 17:19 [entrez]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/11/18 06:00 [medline]
PHST- 2021/06/25 00:00 [pmc-release]
AID - PONE-D-21-00657 [pii]
AID - 10.1371/journal.pone.0253501 [doi]
PST - epublish
SO  - PLoS One. 2021 Jun 25;16(6):e0253501. doi: 10.1371/journal.pone.0253501. 
      eCollection 2021.