Background/Purpose: Outcomes for pediatric patients with lupus nephritis (LN) remain suboptimal. LN may present with thrombotic microangiopathy (TMA) seen on kidney biopsy. Childhood-onset SLE patients with or without TMA often also presents with hematologic disturbances. In LN renal biopsies, subtle endothelial changes that are indicative of TMA may be visualized only via electron microscopy (EM), but ultimately are not classified as overt TMA on the final impression of the pathology report. We theorized that there is an intermediate group of LN biopsies with TMA-like changes only seen by EM, which we referred to as “TMA-EM.To date, there are no studies investigating the frequency, predictors or outcomes of TMA in LN in a pediatric population. This study examined the frequency of TMA and TMA EM in our pediatric LN cohort, as well as the association of hematologic disturbances in these patients. We then examined the association of TMA and TMA-EM on renal outcomes after 1 year of treatment of LN.

Methods: We conducted a single-center, retrospective study of all cases of class III, IV and/or V LN confirmed on kidney biopsy from all pediatric patients seen at Stanford Medicine Childrens Health (July 2003 – Feb 2021). Electron microscopies of LN patients were re-reviewed by a single renal pathologist and patients were placed into 3 distinct categories of renal pathology findings: TMA, TMA-EM or no TMA. The primary outcome variable was type of renal pathology finding in patients with severe hematologic disturbance, mild/moderate disturbance or no disturbance. The secondary outcome variable was renal response after 1 year of treatment in patients with TMA, TMA-EM and no TMA. Fishers exact test was used to assess association between type of hematologic disturbances and renal pathology category. This test was also used to compare renal pathology categories to renal response outcomes (complete renal response, partial response or no response).

Results: There were 88 patients studied: 5 patients (5.7%) with TMA on kidney biopsy, 31 (35.2%) with TMA-EM, and 52 (59.1%) without TMA. We found that the distribution of TMA changes varied with hematologic changes present at the time of biopsy (p = 0.006 [Fishers exact test]). Among patients with no hematologic disturbances, 0% had evidence of TMA on biopsy. Severe hematologic changes were seen in 60.0% of TMA patients, 16.1% of TMA-EM patients and 5.8% of the no TMA patients on biopsy. We found that the distribution of renal response did not vary by TMA status on biopsy (p=0.897). Among patients with no TMA on biopsy, 26.9% showed complete renal response, compared with 59.6% in TMA-EM and 20% in TMA.

Conclusion: Lupus nephritis patients with TMA are more likely to exhibit associated hematologic changes than patients without hematologic disturbances, suggesting the development of TMA is not independent of systemic hematologic changes. TMA-EM does not appear to stand out as a distinct histopathologic grouping resulting in clinical significance. LN patients with TMA and TMA-EM are likely to respond to therapy similarly to those without TMA and there was no significant difference in renal response between the TMA categories.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/thrombotic-microangiopathic-changes-in-kidney-biopsies-of-childhood-onset-systemic-lupus-erythematous-patients-with-and-without-severe-hematologic-disturbances/