Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis
Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis
复制标题
DOI：
10.1093/ndt/15.9.1348
复制
发表时间：
2000-09-01
影响因子：
6.1
通讯作者：
Papadimitriou, M
中科院分区：
文献类型：
--
作者：
Alexopoulos, E;Stangou, M;Papadimitriou, M
背景原发性局灶节段性肾小球硬化症（FSGS）的临床过程各不相同，对于哪些因素在决定预后或治疗反应方面具有重要意义存在相当大的争议。本研究的目的是确定临床，病理学或免疫组化特征，活检，可以确定患者进行性疾病谁可能受益于治疗，并预测长期结果。回顾性分析了33例原发性FSGS成人患者的临床和病理结果，以确定活检特征，这些特征可预测治疗结果或反应。为此，还使用抗细胞内粘附分子-1、C5 b-9、α 3 β 1整联蛋白、α-平滑肌肌动蛋白（SMA）和TGF-β 1的单克隆抗体进行免疫组织化学研究。活检时，17例患者（51%）为肾病，16例（49%）为非肾病。在肾病患者中，11例接受了治疗，6例仅接受了对症治疗。用泼尼松龙（Pred）治疗6-12个月（平均9个月），64%的肾病患者缓解。部分缓解或无效者给予环孢菌素（CsA）或环磷酰胺治疗。在随访结束时（平均57个月），3例肾病患者（28%）完全缓解，6例（54%）部分缓解，2例（18%）对治疗无反应。在7名接受治疗的非肾病患者中，Pred诱导了2名患者（28%）的完全缓解，3名患者（44%）的部分缓解，而2名患者（28%）没有反应。在有反应的肾病患者中，血浆肌酐保持稳定，而在无反应者中几乎翻了一番。在对Pred有反应的非肾病患者中，血浆肌酐也保持不变，而两名无反应者达到终末期肾病（ESRD）。相比之下，50%未经治疗的肾病患者和67%未经治疗的非肾病患者进展为ESRD。多变量分析显示，只有年龄和活检时的血浆肌酐对肾病患者的肾存活率有独立的预测价值。该分析还表明，只有间质纤维化的严重程度才能预测对治疗的反应。此外，C5 b-9、α 3 β 1整联蛋白、α-SMA和TGF-β 1的肾小管间质表达而非肾小球表达在无应答者中显著更广泛，并且与活检时的肾功能相关。然而，只有肾小管间质TGF-β 1的表达与活检时肾功能损害程度独立相关，但上述标志物均不能独立预测肾存活率或治疗反应。伴有FSGS的肾病患者可能受益于更长的Pred疗程。对治疗有反应的肾病患者的肾脏存活率明显高于无反应者。年龄和活检时的血浆肌酐是导致ESRD的独立危险因素。肾小管间质纤维化的严重程度可预测对治疗的反应。
Background. The clinical course of primary focal segmental glomerulosclerosis (FSGS) varies and there is considerable controversy as to which factors are of importance in determining prognosis or response to therapy. The aim of this study was to identify clinical, pathological or immunohistochemical features at biopsy that could identify patients with progressive disease who might benefit from treatment, and predict long-term outcome.Methods. The clinical and pathological findings of 33 adult patients with primary FSGS were retrospectively analysed in order to identify features at biopsy that could be predictive of outcome or response to treatment. For this purpose an immunohistochemical study was also performed, using monoclonal antibodies against intracellular adhesion molecules-1, C5b-9, alpha 3 beta 1 integrin, alpha-smooth-muscle actin (SMA), and TGF-beta 1.Results. At biopsy 17 patients (51%) were nephrotic and 16 (49%) non-nephrotic. Of the nephrotic patients, 11 were treated and six received only symptomatic therapy. Initial treatment with prednisolone (Pred) for 6-12 months (average 9 months) resulted in remission in 64% of nephrotic patients. To those with partial or no response, cyclosporin (CsA) or cyclophosphamide was given. At the end of follow-up (mean 57 months) three nephrotic patients (28%) were in complete remission, six (54%) in partial remission, and two (18%) did not respond to the treatment. In the seven treated non-nephrotic patients, Pred induced a complete remission in two (28%), a partial remission in three (44%), while two patients (28%) did not respond. Plasma creatinine remained stable in nephrotic patients who responded and it almost doubled in non-responders. Plasma creatinine also remained unchanged in treated non-nephrotic patients who responded to Pred, while two non-responders reached end-stage renal disease (ESRD). In contrast, 50% of untreated nephrotic patients and 67% of untreated non-nephrotic patients progressed to ESRD. Multivariate analysis showed only age and plasma creatinine at biopsy to have an independent predictive value for renal survival in nephrotic patients. This analysis also demonstrated that only the severity of interstitial fibrosis predicted the response to the treatment. In addition, the tubulointerstitial but not the glomerular expression of C5b-9, alpha 3 beta 1 integrin, alpha-SMA, and TGF-beta 1 was significantly more extensive in non-responders and correlated with renal function at biopsy. However, only tubulointerstitial expression of TGF-beta 1 independently correlated with the degree of renal function impairment at biopsy, but none of the above markers independently predicted renal survival or response to therapy.Conclusions. Nephrotic patients with FSGS may benefit from a more prolonged course of Pred. Nephrotic patients responding to treatment have a significantly better renal survival than non-responders. Age and plasma creatinine at biopsy are independent risk factors leading to ESRD. The severity of tubulointerstitial fibrosis is predictive of response to therapy.