PMID- 34169210
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 6
IP  - 6
DP  - 2021 Jun
TI  - Enhanced MCP-1 Release in Early Autosomal Dominant Polycystic Kidney Disease.
PG  - 1687-1698
LID - 10.1016/j.ekir.2021.03.893 [doi]
AB  - INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) causes kidney 
      failure typically in adulthood, but the disease starts in utero. Copeptin, 
      epidermal growth factor (EGF), and monocyte chemoattractant protein-1 (MCP-1) are 
      associated with severity and hold prognostic value in adults but remain unstudied 
      in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage 
      infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells 
      is suggested from rodent models. METHODS: In a cross-sectional study, plasma 
      copeptin, urinary EGF, and urinary MCP-1 were evaluated in a pediatric ADPKD 
      cohort and compared with age-, sex-, and body mass index (BMI)-matched healthy 
      controls. MCP-1 was studied in mouse collecting duct cells, human proximal 
      tubular cells, and fetal kidney tissue. RESULTS: Fifty-three genotyped ADPKD 
      patients and 53 controls were included. The mean (SD) age was 10.4 (5.9) versus 
      10.5 (6.1) years (P = 0.543), and the estimated glomerular filtration rate (eGFR) 
      was 122.7 (39.8) versus 114.5 (23.1) ml/min per 1.73 m(2) (P = 0.177) in patients 
      versus controls, respectively. Plasma copeptin and EGF secretion were comparable 
      between groups. The median (interquartile range) urinary MCP-1 (pg/mg creatinine) 
      was significantly higher in ADPKD patients (185.4 [213.8]) compared with controls 
      (154.7 [98.0], P = 0.010). Human proximal tubular cells with a heterozygous PKD1 
      mutation and mouse collecting duct cells with a PKD1 knockout exhibited increased 
      MCP-1 secretion. Human fetal ADPKD kidneys displayed prominent MCP-1 
      immunoreactivity and M2 macrophage infiltration. CONCLUSION: An increase in 
      tubular MCP-1 secretion is an early event in ADPKD. MCP-1 is an early disease 
      severity marker and a potential treatment target.
CI  - (c) 2021 International Society of Nephrology. Published by Elsevier Inc.
FAU - Janssens, Peter
AU  - Janssens P
AD  - PKD Research Group, Laboratory of Pediatrics, Department of Development and 
      Regeneration, KU Leuven, Leuven, Belgium.
AD  - Department of Nephrology, University Hospitals Brussels, Brussels, Belgium.
FAU - Decuypere, Jean-Paul
AU  - Decuypere JP
AD  - PKD Research Group, Laboratory of Pediatrics, Department of Development and 
      Regeneration, KU Leuven, Leuven, Belgium.
FAU - De Rechter, Stephanie
AU  - De Rechter S
AD  - PKD Research Group, Laboratory of Pediatrics, Department of Development and 
      Regeneration, KU Leuven, Leuven, Belgium.
FAU - Breysem, Luc
AU  - Breysem L
AD  - Department of Radiology, University Hospitals Leuven, Leuven, Belgium.
FAU - Van Giel, Dorien
AU  - Van Giel D
AD  - PKD Research Group, Laboratory of Pediatrics, Department of Development and 
      Regeneration, KU Leuven, Leuven, Belgium.
AD  - Laboratory of Ion Channel Research, Department of Cellular and Molecular 
      Medicine, Biomedical Sciences Group, KU Leuven, Leuven, Belgium.
FAU - Billen, Jaak
AU  - Billen J
AD  - Department of Laboratory Medicine, University Hospitals Leuven, Belgium.
FAU - Hindryckx, An
AU  - Hindryckx A
AD  - Department of Obstetrics and Gynecology, KU Leuven, Belgium.
FAU - De Catte, Luc
AU  - De Catte L
AD  - Department of Obstetrics and Gynecology, KU Leuven, Belgium.
FAU - Baldewijns, Marcella
AU  - Baldewijns M
AD  - Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
FAU - Claes, Kathleen B M
AU  - Claes KBM
AD  - Center for Medical Genetics, Ghent University Hospital, Gent, Belgium.
FAU - Wissing, Karl M
AU  - Wissing KM
AD  - Department of Nephrology, University Hospitals Brussels, Brussels, Belgium.
FAU - Devriendt, Koen
AU  - Devriendt K
AD  - Department of Human Genetics, KU Leuven, Leuven, Belgium.
FAU - Bammens, Bert
AU  - Bammens B
AD  - Department of Nephrology, Dialysis and Renal Transplantation, University 
      Hospitals Leuven, Leuven, Belgium.
FAU - Meyts, Isabelle
AU  - Meyts I
AD  - Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology 
      and Transplantation, University Hospitals Leuven, Leuven, Belgium.
AD  - Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University 
      Hospitals Leuven, Leuven, Belgium.
FAU - Torres, Vicente E
AU  - Torres VE
AD  - Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 
      Rochester, Minnesota, USA.
FAU - Vennekens, Rudi
AU  - Vennekens R
AD  - Laboratory of Ion Channel Research, Department of Cellular and Molecular 
      Medicine, Biomedical Sciences Group, KU Leuven, Leuven, Belgium.
FAU - Mekahli, Djalila
AU  - Mekahli D
AD  - PKD Research Group, Laboratory of Pediatrics, Department of Development and 
      Regeneration, KU Leuven, Leuven, Belgium.
AD  - Department of Pediatric Nephrology and Organ Transplantation, University 
      Hospitals Leuven, Leuven, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20210406
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC8207325
OTO - NOTNLM
OT  - ADPKD
OT  - chemokine
OT  - distal tubule
OT  - inflammation
OT  - pediatric nephrology
OT  - proximal tubule
EDAT- 2021/06/26 06:00
MHDA- 2021/06/26 06:01
PMCR- 2021/04/06
CRDT- 2021/06/25 06:56
PHST- 2021/01/01 00:00 [received]
PHST- 2021/03/07 00:00 [revised]
PHST- 2021/03/22 00:00 [accepted]
PHST- 2021/06/25 06:56 [entrez]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/06/26 06:01 [medline]
PHST- 2021/04/06 00:00 [pmc-release]
AID - S2468-0249(21)01041-X [pii]
AID - 10.1016/j.ekir.2021.03.893 [doi]
PST - epublish
SO  - Kidney Int Rep. 2021 Apr 6;6(6):1687-1698. doi: 10.1016/j.ekir.2021.03.893. 
      eCollection 2021 Jun.