Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) localization in renal biopsies

sFlt‐1 is a splice variant of the vascular endothelial growth factor (VEGF) receptor lacking the transmembrane and cytoplasmic domains and acts as a powerful antagonist of VEGF, thereby inhibiting VEGF signaling in the vasculature. Its excess can diminish and alter fenestrated capillary beds and it is considered causal in preeclampsia, but its presence is a physiologically necessity for limiting capillary growth in the vitreous and other compartments within the eye . Plasma sflt1 levels are higher in patients with chronic kidney disease (CKD) and using multivariate regression analysis were exclusively associated with renal function (higher levels correlate with decreasing function) [PMID: 19608702]. The source of this plasma sFlt‐1 is unclear, but circulating monocytes have been considered a possible etiology. 47 renal biopsies were immunostained for sFlt‐1 and evaluated on a 0–4 grading scale of positive cells within inflammatory infiltrates: 4 drug‐induced interstitial nephritis; 12 allografts, 3 with polyomavirus nephritis; 10 diabetes mellitus; 6 lupus glomerulonephritis; 5 ANCA; 5 IgA/HSP nephropathy and 5 miscellaneous chronic kidney diseases. 42 had infiltratory infiltrates of which 31 had sflt positive cells: 3 biopsies had cells which constituted more that 50% of the inflammatory infiltrate (grade 4), 6 biopsies 25–50% (grade 3), 4 biopsies 10–25% (grade 2), 3 biopsies 10% (grade1) and 15 biopsies <10% (grade +/−). The positive cells were generally single but formed clusters that became diffuse. The associated capillary network (immunostaining for CD34) was reduced or had disappeared. This data was supported by RT‐PCR analysis of sFlt‐1 in a subset of frozen biopsy samples. CD68 stains indicated that the positive cells were histiocytes/transitioning myofibroblasts such as seen in [PMID: 28209809]. In general, there was a correlation (r 2 = 0.89) between degree of inflammation and sFlt‐1 positive cells, but some inflammatory foci were negative; and no correlation was seen between inflammation and fibrotic changes ( perhaps indicating that the fibrotic changes might be an ongoing/evolving process ) . Cases of polyomavirus nephritis (2), drug‐associated interstitial nephritis (3), advanced diabetic kidneys (3) and HSP(1) were the most positive (9/47), but significant (10% or greater) sFlt‐1 positivity was seen in many biopsies (16/47). In conclusion, sFlt‐1 positive cells are generally part of the inflammatory infiltrates in CKD and may be extremely abundant. Their presence promotes an anti‐angiogenic state that could inhibit capillary repair, contribute to peritubular capillary loss and enhance fibrosis in CKD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .