Ruggenenti Piero, Chiurchiu Carlos, Abbate Mauro, Perna Annalisa, Cravedi Paolo, Bontempelli Mario, Remuzzi Giuseppe
Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy.
Clin J Am Soc Nephrol. 2006 Jul;1(4):738-48. doi: 10.2215/CJN.01080905. Epub 2006 Jun 14.
Rituximab effectively reduces proteinuria in patients with idiopathic membranous nephropathy (IMN), but response to treatment may vary from patient to patient. The association between baseline clinical, laboratory, and histology covariates and proteinuria reduction was evaluated retrospectively by multiple linear regression analysis at 3 mo after rituximab therapy in 14 patients with IMN with proteinuria > 3.5 g/24 h while on angiotensin-converting enzyme inhibition for at least 6 mo and no previous remissions. The association strength was expressed by standardized beta coefficients (SbetaC). Glomerular (SbetaC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SbetaC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SbetaC = 0.59, P = 0.003) and interstitial fibrosis (SbetaC = 0.60, P = 0.001) were significantly associated with 3-mo proteinuria. Urinary protein excretion decreased from 9.1 +/- 4.0 to 4.6 +/- 3.5 g/24 h (P < 0.001) in eight patients with TI score 1.7 but did not change in six with a score > or = 1.7. Nine additional patients with IMN then were allocated prospectively to rituximab treatment on the basis of a TI score < 1.7. Three-month proteinuria decreased in all patients from 8.9 +/- 5.3 to 4.9 +/- 3.9 g/24 h (P < 0.001) and serum albumin increased from 2.2 +/- 0.6 to 2.8 +/- 0.5 mg/dl (P < 0.01). Changes in serum albumin and cholesterol were inversely correlated (P < 0.02, r = -0.44). Rituximab achieved CD20 and CD19 depletion in all patients. In patients with IMN and nephrotic proteinuria despite angiotensin-converting enzyme inhibition therapy, renal biopsy findings may help in predicting response to rituximab and defining selection criteria for randomized trials that aim to assess the risk/benefit profile of B cell target therapy as compared with aspecific immunosuppressants and/or conservative therapy alone.
利妥昔单抗可有效降低特发性膜性肾病（IMN）患者的蛋白尿，但治疗反应可能因患者而异。对14例蛋白尿>3.5 g/24 h、接受血管紧张素转换酶抑制剂治疗至少6个月且既往无缓解的IMN患者，在利妥昔单抗治疗3个月后，通过多元线性回归分析回顾性评估基线临床、实验室和组织学协变量与蛋白尿降低之间的关联。关联强度用标准化β系数（SbetaC）表示。肾小球（SbetaC = 0.48，P = 0.049）和肾小管间质（TI）评分（SbetaC = 0.61，P = 0.003）可预测治疗结果。在肾小球和TI评分成分中，肾小管萎缩（SbetaC = 0.59，P = 0.003）和间质纤维化（SbetaC = 0.60，P = 0.001）与3个月时的蛋白尿显著相关。TI评分为1.7的8例患者尿蛋白排泄量从9.1±4.0降至4.6±3.5 g/24 h（P < 0.001），而评分≥1.7的6例患者尿蛋白排泄量未改变。另外9例IMN患者随后根据TI评分<1.7被前瞻性分配接受利妥昔单抗治疗。所有患者3个月时蛋白尿从8.9±5.3降至4.9±3.9 g/24 h（P < 0.001），血清白蛋白从2.2±0.6升至2.8±0.5 mg/dl（P < 0.01）。血清白蛋白和胆固醇的变化呈负相关（P < 0.02，r = -0.44）。所有患者均实现了CD20和CD19耗竭。对于尽管接受血管紧张素转换酶抑制剂治疗仍有肾病性蛋白尿的IMN患者，肾活检结果可能有助于预测对利妥昔单抗的反应，并为旨在评估B细胞靶向治疗与非特异性免疫抑制剂和/或单纯保守治疗相比的风险/获益情况的随机试验确定选择标准。
