Glomerular Expression of Some Profibrotic Factors in Progressive Childhood Lupus Nephritis

Lupus nephritis (LN) is a major cause of mortality and morbidity in both adult and pediatric patients. However, studies regarding pathogenesis and predictors of renal outcomes in childhood LN are limited. Transforming growth factor-β1 (TGF-β1) and Connective tissue growth factor (CTGF) have an important role in proliferative and fibrotic changes in many renal diseases. We aim to evaluate the role of such two profibrotic factors in the progression of childhood onset LN and to detect if their glomerular expression could represent an early predictor of future deterioration of renal function.

34 children with new onset of LN were included. Glomerular expressions of TGF-β1 and CTGF were evaluated by immunohistochemical analysis in the renal tissue of such patients and in control tissue. GFR was estimated at time of renal biopsy at the onset of LN and after 2 years of follow-up. Rate of GFR change (ΔGFR) was calculated and used as indicative of degree of renal disease progression.

Glomerular TGF-β1 and CTGF expressions in children with LN were significantly higher than in control tissue (LN 15.41 ± 9.84 and 15.56 ± 10.51 vs. 2.15 ± 1.45 and 1.35 ± 1.07 in control respectively, with p < 0.001 in both). In addition, the glomerular expressions of TGF-β1 and CTGF were significantly higher in patients with further decline in GFR (20.68 ± 7.73 and 21.05 ± 8.75) versus (5.75 ± 4.37 and 5.50 ± 3.78) in those without change in GFR with (p = 0.000 for both of them).

Patients with LN have increased glomerular expressions of TGF-β1 and CTGF, which were higher in those with further decline in GFR. These profibrotic factors are suspected to be involved in pathogenesis of LN and could be evaluated as a target for therapeutic intervention to stop progression of LN. In addition, their glomerular expression could be used as an early predictor of progression of LN, to justify early aggressive therapy in those with suspected rapid progression.