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Abstract: FR-PO1009

The VEGF Inhibitor Soluble FLT1 Does Not Aggravate AKI-to-CKD Transition

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms


  • Van Aanhold, Cleo Christina lioe, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Koudijs, Angela, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Dijkstra, Kyra L., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • van Kooten, Cees, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Bruijn, Jan A., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Baelde, Hans J., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Soluble Fms-like tyrosine kinase 1 (sFLT1) is an endogenous VEGF inhibitor. sFLT1 critically maintains the podocyte cytoskeleton and has anti-inflammatory effects in diabetic kidney disease (DKD). However, sFLT1 has also been related to peritubular capillary (PTC) loss which contributes to chronic kidney damage following acute kidney injury (AKI-to-CKD transition). Here, we studied whether overexpression of sFLT1 aggravates experimental AKI-to-CKD transition and whether sFLT1 is increased in human kidney fibrosis.


Mice were transfected with a sFlt1 DNA construct via electroporation. After confirming transfection efficacy, control and sFLT1-treated mice underwent renal unilateral IRI and were sacrificed after 28 days; untreated mice underwent sham surgery. Serum KIM-1 was measured by ELISA. Sirius red, F4/80 and endomucin stainings were quantified in renal cortex and medulla. Glomerular and cortical sFLT1-i13 mRNA expression was measured in biopsies obtained from DKD patients (n=23) and unaffected tumour-nephrectomy tissues as a control (n=14).


At 48h after IRI, serum KIM-1 was increased compared to sham and baseline; however, sFLT1 did not affect serum KIM-1, indicating similar levels of AKI in sFLT1 and control mice. One month after IRI, cortical and medullary fibrosis and the number of macrophages were increased compared to sham; the PTC number was decreased in IRI mice. Overexpression of sFLT1 did not increase the amount of fibrosis or renal macrophages in IRI mice; further, sFLT1 had no effect on the PTC number in IRI mice. Finally, sFLT1 mRNA levels were similar in fibrotic and normal kidney biopsies; in fibrotic kidney cortex tissues, high sFLT1 levels correlated with increased thrombomodulin and decreased syndecan-1 mRNA levels, which may reflect renal endothelial protection.


sFLT1 does not aggravate experimental AKI-to-CKD transition: sFLT1 has no effect on chronic renal fibrosis, macrophage infiltration and PTC loss after IRI. Moreover, sFLT1 expression is not increased in human CKD; in contrast, renal sFLT1 levels are correlated with markers of nephroprotection. Because we previously found that sFLT1 has profound anti-inflammatory potential in DKD, our findings suggest that sFLT1 can be administered at a therapeutically effective dose without aggravating maladaptive kidney damage.