[Molecular factors of angiogenesis in renal tissue of patients with chronic glomerulonephritis: association with nephrosclerosis and anemia].
OBJECTIVE
To study correlations between accumulation of angiogenesis molecular factors (hypoxia-inducible factor-1alpha - HIF-1alpha, vascular endothelial growth factor - VEGF, thrombospondin - TSP-1) in kidney biopsy tissue from chronic glomerulonephritis (CGN) patients and severity of nephrosclerosis, obliteration of renal capillary bed, filtration dysfunction and anemia.


METHODS
We examined 22 patients with marked proteinuria (2.77; 5.7, mean 4.2 g/ day). Half of the patients had nephrotic syndrome. Glomerular filtration rate (GFR) by Cochroft-Golt formula was 68 (53;84) ml/min/1.73 m2. According to renal biopsy findings, CGN was detected in 19 patients, 2 patients had lupus nephritis (LN), 1 patient had renal amyloidosis. Nineteen CGN patients were divided into two groups by nephrosclerosis severity: group 1-7 patients with moderate nephrosclerosis, group 2-12 patients with severe nephrosclerosis. Cryostate sections of renal biopsy tissue samples were studied immunohistochemically using monoclonal antibodies to HIF-1alpha, VEGF, TSP-1, CD34. The reaction intensity was assessed by 6-point scale semiquantitative method.


RESULTS
Response to HIF-1alpha was stronger in the tubular epithelium than in glomeruli. No correlation was observed between accumulation of HIF-1alpha in the glomeruli and tubular epithelium. Intensity of glomerular staining correlated with severity of proteinuria (Rs = 0.63, p < 0.05), intensity of HIF-1alpha accumulation in tubular epithelium correlated with duration of the kidney disease (Rs = 0.74, p < 0.001), duration of persistent arterial hypertension (Rs = 0.68, p < 0.05) and severity of nephrosclerosis. VEGF and TSP-1 were found in equal quantity both in the glomeruli and renal interstitium. CGN patients with marked nephrosclerosis had lower accumulation of VEGF and higher TSP-1 in the interstitium. No correlation was found between intensity of tubular epithelium response to HIF-1alpha and accumulation of VEGF in the interstitium. Patients with severe nephrosclerosis demonstrated weaker staining of tubulointerstitium to CD34, reflecting the degree of its vascularisation. Significant correlation between CD34 and expression of HIF-1alpha, VEGF, TSP-1 was not registered. In patients with low intensity of tubular epithelial staining to HIF-1alpha (less than 2 points) anemia was detected in 63% versus 18% in patients with more intensive accumulation.


CONCLUSIONS
CGN progression is associated with development of renal tubulointerstitial ischemia. High tubular production of HIF-1alpha was not accompanied with activation of VEGF accumulation in renal interstitium but was associated with reduced risk of anemia in CGN patients with manifest nephrosclerosis.
M Iu
MIu
Shvetsov
A A
AA
Ivanov
A V
AV
Kuznetsova
O P
OP
Popova
A S
AS
Rameeva
D000328:Adult; D000740:Anemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009400:Nephrosclerosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A