Different response of urinary excretion of VEGF in patients with chronic and acute renal failure

Abstract

To the Editor: Vascular endothelial growth factor (VEGF) is constitutively expressed by epithelial cells of a nephron from embryonic to adult kidneys. In renal disease, VEGF appears to be involved in a repair of the glomerulus1.Ostendorf T. Kunter U. Eitner F. et al.VEGF(165) mediates glomerular endothelial repair.J Clin Invest. 1999; 104: 913-923Crossref PubMed Scopus (272) Google Scholar. It is excreted in urine2.Honkanen E. Teppo A.-M. Grönhagen-Riska C. Decreased urinary excretion of vascular endothelial growth factor in idiopathic membranous glomerulonephritis.Kidney Int. 2000; 57: 2343-2349Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar and is suspected to be secreted from tubular cells by hypoxic stimulation in vitro3.Awad B.L. Kreft B. Wolber E.-M. et al.Hypoxia and interleukin-1β stimulate vascular endothelial growth factor production in human proximal tubular cells.Kidney Int. 2000; 58: 43-50Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar,4.Kanellis J. Mudge S. Fraser S. et al.Redistribution of cytoplasmic VEGF to the basolateral aspect of renal tubular cells in ischemia-reperfusion injury.Kidney Int. 2000; 57: 2445-2456Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar and in vivo4.Kanellis J. Mudge S. Fraser S. et al.Redistribution of cytoplasmic VEGF to the basolateral aspect of renal tubular cells in ischemia-reperfusion injury.Kidney Int. 2000; 57: 2445-2456Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar. Thus, because the amount of urinary VEGF might reflect renal hypoxia, we measured it in patients with renal diseases and various renal functions. A total of 29 urine and 26 serum and plasma samples were collected from 22 non-diabetic non-nephrotic patients without serious complications. Fifteen patients had a renal biopsy (11 with IgA nephropathy, two with membranous nephropathy, one with focal segmental glomerulosclerosis, and one with membranoproliferative glomerulonephritis). The other seven patients were clinically diagnosed with chronic renal failure. Twelve urine and serum samples were collected from three patients with ischemic acute renal failure. As VEGF concentration in the urine did not change after 24 hours' incubation at room temperature, those urine samples were stored at -30°C until use and submitted to colorimetric enzyme immunoassay to quantitate VEGF. Renal function was evaluated by 24-hour creatinine clearance (CCr). There was an inverse relationship between urinary excretion of VEGF and CCrFigure 1a. VEGF excretion in urine did not correlate with its serum Figure 1b or plasma level (data not shown). In patients with acute renal failure, no correlation was observed between urinary excretion of VEGF and CCrFigure 1c. We examined patients with a wide range of renal functions to focus on the relationship between urinary VEGF and renal function. In patients with chronic renal failure, VEGF excretion in urine increased as renal function decreased. Since excretion was independent of the serum level of VEGF, urinary VEGF appears to be derived from the kidney. Therefore, increased excretion of VEGF suggests its increased secretion in residual nephrons under diffuse and continuous hypoxia. In patients with acute renal failure, urinary VEGF excretion was independent of renal function, probably because excretion of VEGF from the kidney did not change much since the ischemic period was transient and the area was limited. Although further studies are needed, urinary VEGF might be a unique indicator of renal hypoxia. This study was supported in part by the grant from the Ministry of Health and Welfare, Japan.