The course of proliferative lupus nephritis is characterized by flares of activity alternating with periods of quiescence against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serologic, and histologic tools to evaluate disease activity and how they may be applied to redefine the treatment goals in lupus nephritis. Traditionally, treatment response is judged by the degree of proteinuria reduction and improvement of kidney function, but this fails to differentiate ongoing inflammatory disease from chronic damage. Despite intensive research, no novel biomarker has proved useful for clinical practice, and we continue to rely on anti–double-stranded DNA antibody levels to assess serologic activity. Repeat kidney biopsies sometimes reveal persistent inflammation despite apparent clinical remission, giving credibility to the conviction that histologic remission should be a treatment goal and protocol biopsies be part of the decision-making process. However, the discrepancies between clinical and histologic responses to therapy can be explained by persistent systemic autoimmunity with low-grade immune complex deposition or, alternatively, by delayed clearance of intrarenal inflammation once immunologic remission has been achieved. Because persistent immune dysregulation is the motor of disease activity in lupus nephritis, it should be the principal focus of therapy and monitoring. We propose to replace the traditional induction-remission maintenance protocol by a more dynamic and individualized approach and aim for 3 treatment goals, concomitantly rather than sequentially: (i) clinical remission, by attenuating renal inflammation, using microscopic hematuria, proteinuria, estimated glomerular filtration rate, and complement levels as biomarkers; (ii) immunologic remission, by decreasing immune complex generation, using anti–double-stranded DNA antibody as a biomarker; and (iii) preservation of kidney function, by curtailing chronic kidney damage, using estimated glomerular filtration rate slope as a biomarker.

中文翻译：

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狼疮性肾炎：重新定义治疗目标


增生性狼疮性肾炎的病程特征是在慢性免疫失调的背景下，活动突然发作与静止期交替出现。准确评估疾病活动度对于定制治疗具有无懈可击的重要性。在本通讯中，我们讨论了用于评估疾病活动的可用临床、血清学和组织学工具，以及如何应用它们来重新定义狼疮性肾炎的治疗目标。传统上，治疗反应是根据蛋白尿减少和肾功能改善的程度来判断的，但这无法区分持续的炎症性疾病和慢性损伤。尽管进行了深入的研究，但没有新的生物标志物被证明对临床实践有用，我们继续依靠抗双链 DNA 抗体水平来评估血清学活性。重复肾活检有时显示持续性炎症，尽管临床有明显的缓解，这让人们相信组织学缓解应该是一个治疗目标，并且方案活检是决策过程的一部分。然而，临床和组织学对治疗反应之间的差异可以通过持续的全身性自身免疫伴低级别免疫复合物沉积来解释，或者，一旦达到免疫缓解，肾内炎症的清除延迟即可解释。由于持续性免疫失调是狼疮性肾炎疾病活动的运动，因此它应该是治疗和监测的主要重点。 我们建议用一种更动态和个体化的方法取代传统的诱导缓解维持方案，并同时而不是按顺序实现 3 个治疗目标：（i） 临床缓解，通过减轻肾脏炎症，使用显微镜血尿、蛋白尿、估计的肾小球滤过率和补体水平作为生物标志物;（ii） 免疫缓解，通过使用抗双链 DNA 抗体作为生物标志物，通过减少免疫复合物的产生;（iii） 使用估计的肾小球滤过率斜率作为生物标志物，通过减少慢性肾损伤来保存肾功能。