Department of Pediatrics, Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Rheumatology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Nephrol Dial Transplant. 2023 May 31;38(6):1469-1476. doi: 10.1093/ndt/gfac286.
End-stage kidney disease (ESKD) from lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Kidney biopsy is the gold standard for diagnosis and prognostication of LN. While interstitial fibrosis and tubular atrophy (IFTA) predict progression to ESKD, the National Institutes of Health (NIH) classification of interstitial inflammation in unscarred cortical parenchyma is not predictive of chronic kidney disease (CKD) progression. The objective of this study was to determine whether total cortical interstitial inflammation that accounts for inflammation in the entire cortical parenchyma could predict CKD progression in patients with LN. Early identification of at-risk patients may improve outcomes.
This retrospective cohort study included 125 SLE patients with LN class III, IV, V or mixed (III/V, IV/V) on the index biopsy (2005-2018). Kidney biopsies were reviewed and assigned based on the 2018 NIH Activity Index (AI) and tubulointerstitial lesion categories. Total interstitial inflammation in the entire cortical parenchyma was graded as 0, 1, 2 or 3, corresponding to <10%, 10-25%, 26-50% and >50%, respectively, of the total cortical parenchyma containing an inflammatory infiltrate (similar to the definition used in the Banff total inflammation score). CKD progression was defined as an estimated glomerular filtration rate decrease of ≥30% within 5 years after the index biopsy. Kaplan-Meier survival curves and Cox proportional hazards models were performed to compare the two scoring systems, the total cortical intestinal inflammation score and the NIH interstitial inflammation score as predictors of CKD progression.
Of 125 patients, 46 experienced CKD progression; 21 of 46 subsequently developed ESKD, 28 (22.4%) had moderate-severe total cortical interstitial inflammation and 8 (6.4%) had moderate-severe NIH interstitial inflammation. There were no differences in baseline characteristics between progressors and nonprogressors. Total cortical interstitial inflammation was associated with CKD progression in time-dependent analyses [hazard ratio 2.45 (95% confidence interval 1.2-4.97)] adjusted for age at biopsy, race, sex, LN class and hypertensive vascular change on kidney biopsy. The NIH interstitial inflammation was not associated with CKD progression.
In contrast to the current NIH interstitial inflammation classification, accounting for interstitial inflammation in the entire cortical parenchyma allows identification of patients at risk for CKD progression in LN.
狼疮性肾炎（LN）导致的终末期肾病（ESKD）是系统性红斑狼疮（SLE）患者发病率和死亡率的主要原因。肾脏活检是 LN 诊断和预后的金标准。虽然间质纤维化和肾小管萎缩（IFTA）可预测向 ESKD 进展，但无瘢痕皮质实质中未受损的间质炎症的美国国立卫生研究院（NIH）分类不能预测慢性肾脏病（CKD）的进展。本研究的目的是确定是否可以预测 LN 患者的 CKD 进展。
本回顾性队列研究纳入了 125 例在指数活检时为 LN Ⅲ、Ⅳ、Ⅴ 或混合（Ⅲ/Ⅴ、Ⅳ/Ⅴ）的 SLE 患者（2005-2018 年）。对肾脏活检进行了回顾性分析，并根据 2018 年 NIH 活动指数（AI）和肾小管间质病变分类进行了分级。将整个皮质实质中的总间质炎症分为 0、1、2 或 3 级，分别对应于包含炎症浸润的皮质实质的<10%、10-25%、26-50%和>50%（类似于 Banff 总炎症评分的定义）。CKD 进展定义为指数活检后 5 年内估计肾小球滤过率下降≥30%。进行 Kaplan-Meier 生存曲线和 Cox 比例风险模型分析，比较总皮质间质炎症评分和 NIH 间质炎症评分作为 CKD 进展的预测因子。
在 125 例患者中，46 例发生 CKD 进展；其中 21 例随后发展为 ESKD，28 例（22.4%）存在中度至重度总皮质间质炎症，8 例（6.4%）存在中度至重度 NIH 间质炎症。进展者和非进展者的基线特征无差异。总皮质间质炎症与时间依赖性分析中的 CKD 进展相关[危险比 2.45（95%置信区间 1.2-4.97）]，调整了活检时的年龄、种族、性别、LN 类型和肾脏活检上的高血压血管改变。NIH 间质炎症与 CKD 进展无关。
与当前的 NIH 间质炎症分类相比，评估整个皮质实质的间质炎症可以识别出有 CKD 进展风险的 LN 患者。
