Enhanced MCP-1 Release in Early Autosomal Dominant Polycystic Kidney Disease

Peter Janssens, Jean Paul Decuypere, Stéphanie De Rechter, Luc Breysem, Dorien Van Giel, Jaak Billen, An Hindryckx, Luc De Catte, Marcella Baldewijns, Kathleen B.M. Claes, Karl M. Wissing, Koen Devriendt, Bert Bammens, Isabelle Meyts, Vicente E. Torres, Rudi Vennekens, Djalila Mekahli

Research output: Contribution to journalArticlepeer-review

Abstract

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 m2 (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.

Original languageEnglish (US)
JournalKidney International Reports
DOIs
StateAccepted/In press - 2021

Keywords

  • ADPKD
  • chemokine
  • distal tubule
  • inflammation
  • pediatric nephrology
  • proximal tubule

ASJC Scopus subject areas

  • Nephrology

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