The correlation of vascular endothelial growth factor and renal pathology in lupus nephritis

Abstract

Vascular endothelial growth factor (VEGF) plays a pivotal role in delayed progression of renal diseases such as remnant kidney model and thrombotic microangiopathy. It protects vascular endothelial and tubular epithelial cells from apoptosis, hypoxia and inflammation. This study determines an association between intra-renal VEGF gene expression and short-term renal outcome in SLE patient with active lupus nephritis. Forty-one renal biopsy samples from lupus nephritis patients were studied by real-time polymerase chain reaction and immunohistochemistry. The same renal biopsy core was used to study both VEGF expression and histopathology. Most patients had received the standard immunosuppressive treatment. The VEGF gene expression was normalized by 18s rRNA. Receiver operating characteristic (ROC) curves analysis was used to define the cutoff level of VEGF. The outcomes at 6-month post-treatment were doubling serum creatinine and end-stage renal disease (ESRD). All data were expressed as median and inter-quartile range (IQR). The median age (IQR) of patients was 29.5 (34-23) years. The 24-hour urinary protein excretion was 2.0 (3.61-1.11) gram/day and erythrocyturia was 12 (40-1) cell/HPF. The serum creatinine was 1.0 (2.2-0.7) mg/dl. Eighty percent biopsy samples were classified in focal or diffuse proliferative lupus nephritis. The activity and chronicity indices were 5 (11-0.5) and 2 (6-1), respectively. VEGF gene expression was significantly decreased as compared to kidney control (kidney transplant donors) (0.83 ± 0.7 vs. -0.001± 0.39 log copies; p = 0.002). VEGF gene expression was inversely associated with high percentage (≥19%) of glomerular endocapillary proliferation (p=0.01), crescentic formation (p=0.04) and high activity index (p=0.03). The levels of intra-renal VEGF mRNAs at biopsy could predict ESRD, doubling serum creatinine or combination of both outcomes (p-value = 0.01, 0.04 and 0.005, respectively). In conclusion, intra-renal expression of VEGF is inversely associated with severe pathologic changes of lupus nephritis. The decreased VEGF levels were associated with poor renal outcomes. This may lead to the novel molecular classification which may be complement to the current diagnostic method of renal biopsy.