Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Lupus Sci Med. 2022 Apr;9(1). doi: 10.1136/lupus-2022-000684.
Treatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of proteinuria. Using estimated glomerular filtration rate (eGFR) trajectories, we characterised early chronic kidney disease in LN and examined whether certain patients continue to accrue renal damage despite proteinuric response.
We conducted a single-centre study of patients diagnosed with their first episode of biopsy-proven class III, IV, and/or V LN (n=37). For each patient, eGFR trajectory was graphed over 5 years following renal biopsy. Participants were divided into those with progressive eGFR loss (eGFR slope <-5 mL/min/1.73 m/year) versus those with stable eGFR. Participant demographics, renal biopsy features and response status at 1 year (urine protein to creatinine ratio <500 mg/g) were compared between eGFR trajectory groups.
Overall, 30% (n=11) of participants accrued progressive eGFR loss despite standard of care therapy over the first 5 years following renal biopsy. There were no significant differences in baseline renal biopsy features, medication regimens or comorbidities between eGFR trajectory groups. Resolution of proteinuria at 1 year did not differentiate between groups: 6 of 18 (33%) of complete responders continued to accrue renal damage compared with 5 of 17 (29%) of non-responders. Response status could not be assigned for two participants in the stable eGFR group due to missing clinical information at 1 year.
We identified an understudied category of patients with LN who accrue progressive renal damage despite apparent response to standard of care therapy. Better definitions and biomarkers of response are needed to improve renal outcomes and trial design.
狼疮肾炎 (LN) 的治疗反应基于蛋白尿定义,但基于方案的肾活检研究表明,即使没有蛋白尿,患有狼疮的患者也可能存在活动性肾炎。本研究通过估计肾小球滤过率(eGFR)轨迹,描述 LN 患者的早期慢性肾脏病,并探讨尽管蛋白尿反应良好,但某些患者是否会继续发生肾脏损伤。
我们对首次经肾活检确诊为 III 、 IV 和/或 V 型 LN 的患者进行了单中心研究(n=37)。对于每位患者,在肾活检后 5 年内绘制 eGFR 轨迹图。根据 eGFR 斜率(eGFR slope <-5 mL/min/1.73 m/year)将参与者分为 eGFR 下降组和 eGFR 稳定组。比较两组患者的人口统计学特征、肾活检特征和 1 年时的反应状态(尿蛋白与肌酐比值 <500 mg/g)。
总体而言,在肾活检后 5 年内,尽管采用了标准治疗,但仍有 30%(n=11)的患者出现 eGFR 持续下降。eGFR 轨迹组之间在基线肾活检特征、药物治疗方案或合并症方面均无显著差异。1 年时蛋白尿的缓解情况并不能区分两组:18 名完全缓解者中有 6 名(33%)继续发生肾脏损伤,而 17 名非缓解者中有 5 名(29%)。由于在 1 年时缺少临床信息,稳定 eGFR 组中的 2 名参与者无法确定其反应状态。
我们发现了一类 LN 患者,尽管对标准治疗有明显反应,但仍会发生进行性肾脏损伤,这一现象尚未得到充分研究。需要更好的反应定义和生物标志物来改善肾脏结局和试验设计。