From the Pediatrics Department, Pediatric Nephrology and Dialysis Unit, Faculty of Medicine, Assiut University Children Hospital, Assiut University, Assiut, Egypt.
Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
J Clin Rheumatol. 2020 Dec;26(8):305-312. doi: 10.1097/RHU.0000000000001118.
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.
狼疮性肾炎（LN）是成人和儿童患者死亡和发病的主要原因。然而，关于儿童 LN 的发病机制和肾脏结局预测因素的研究有限。转化生长因子-β1（TGF-β1）和结缔组织生长因子（CTGF）在许多肾脏疾病的增殖和纤维化变化中具有重要作用。我们旨在评估这两种促纤维化因子在儿童 LN 进展中的作用，并检测其肾小球表达是否可以作为未来肾功能恶化的早期预测指标。
纳入 34 例新诊断为 LN 的儿童。通过免疫组织化学分析评估这些患者和对照组肾组织中 TGF-β1 和 CTGF 的肾小球表达。在 LN 发病时和 2 年随访时，通过肾小球滤过率（GFR）估计来评估 GFR。计算 GFR 变化率（ΔGFR），作为肾脏疾病进展程度的指标。
LN 患儿的肾小球 TGF-β1 和 CTGF 表达明显高于对照组（LN 为 15.41 ± 9.84 和 15.56 ± 10.51，对照组为 2.15 ± 1.45 和 1.35 ± 1.07，均<0.001）。此外，肾小球 TGF-β1 和 CTGF 的表达在 GFR 进一步下降的患者中明显高于 GFR 无变化的患者（分别为 20.68 ± 7.73 和 21.05 ± 8.75，与 5.75 ± 4.37 和 5.50 ± 3.78，均<0.001）。
LN 患者肾小球 TGF-β1 和 CTGF 的表达增加，GFR 进一步下降的患者表达更高。这些促纤维化因子可能参与 LN 的发病机制，并可作为治疗干预的靶点，以阻止 LN 的进展。此外，它们的肾小球表达可作为 LN 进展的早期预测指标，以便在疑似快速进展的患者中尽早进行积极治疗。
