Soluble fms-like tyrosine kinase 1 localization in renal biopsies of chronic kidney disease

Abstract Background Soluble fms-like tyrosine kinase 1 (sFLT1) 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 signaling. Plasma sFLT1 levels are higher in patients with chronic kidney disease (CKD) and correlate with renal dysfunction. The source of plasma sFLT1 in CKD is unclear. Methods 52 renal biopsies were studied for sFLT1 expression using immunohistochemistry and evaluated on a 0-4 grading scale of positive cells within inflammatory infiltrates. These included - drug-induced interstitial nephritis (6); allografts (12), with polyomavirus nephritis (3); diabetes mellitus (10); lupus glomerulonephritis (6); pauci-immune vasculitis (7); IgA nephropathy (6) and miscellaneous CKD (5). Results 47 biopsies had inflammatory infiltrates of which 37 had sFLT1 positive cells: 3 biopsies had cells which constituted more that 50% of the inflammatory infiltrate (grade 4), 9 biopsies 25- 50% (grade 3), 5 biopsies 10-25% (grade 2), 3 biopsies 10% (grade1) and 17 biopsies Conclusions sFLT1 positive histiocytes are generally part of the inflammatory infiltrates noted in CKD and particularly abundant in forms of interstitial nephritis. Their presence promotes an anti-angiogenic state locally in the tubulointerstitium that could inhibit capillary repair, contribute to peritubular capillary loss and enhance fibrosis in CKD.