Moderate to severe interstitial inflammation in the kidney cortex at first biopsy predicts chronic kidney disease (CKD) progression in patients with lupus nephritis, a recent study finds.

Investigators assessed interstitial inflammation on index kidney biopsies from 125 patients. They compared 3 methods: the National Institutes of Health (NIH) Activity Index, the NIH interstitial inflammation classification, and the Banff kidney allograft rejection classification of total cortical interstitial inflammation. The NIH interstitial inflammation classification currently excludes interstitial fibrosis and tubular atrophy (IFTA), whereas the Banff classification includes interstitial inflammation with and without IFTA. Total interstitial inflammation was graded as 0, 1, 2 or 3, corresponding to less than 10%, 10%-25%, 26%-50%, and more than 50%, respectively, of the total cortical parenchyma with inflammation. Investigators categorized inflammation as “none to mild” or “moderate to severe” using each method.

CKD progression defined as a 30% or greater decline in estimated glomerular filtration rate within 5 years occurred in 46 patients (37%), including 21 patients (17%) who progressed to end-stage kidney disease (ESKD), Minh Dien Duong, MD, MS, of Montefiore, Albert Einstein College of Medicine in Bronx, New York, and colleagues reported in Nephrology Dialysis Transplantation. Of the 3 classification methods, only the Banff-based total cortical interstitial inflammation score was prognostic. A significantly higher proportion of progressors (34.8%) than nonprogressors (15.2%) had a moderate to severe total cortical interstitial inflammation score.

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In an adjusted Kaplan-Meier analysis, a moderate-to-severe total cortical interstitial inflammation score was significantly associated with a 2.5-fold increased risk of CKD progression compared with a score of none to mild. The investigators adjusted the analysis for age at biopsy, sex, race, lupus nephritis class, and hypertensive vascular changes.

“This study underscored the need to modify the existing NIH definition of interstitial inflammation to account for inflammation in areas with and without fibrosis,” Dr Duong’s team concluded. “This modification may help identify and treat at-risk patients before irreversible chronic changes develop.”

According to the investigators, it is important to identify cortical interstitial inflammation early in the kidneys of patients with systemic lupus erythematosus, before irreversible fibrosis, so more aggressive treatments can be given to prevent progression to CKD and ESKD.

“Using the total interstitial inflammation score may identify patients at risk for progression and thus lead to more aggressive therapy and better control of the disease outcome,” Dr Duong and colleagues wrote.

The investigators acknowledged that the study was underpowered to detect significant differences in CKD progression using an IFTA score alone from the first biopsy. IFTA cannot be reversed with current therapies.


Duong MD, Wang S, Schwartz D, Mowrey WB, Broder A, Goilav B. Total cortical interstitial inflammation predicts chronic kidney disease progression in patients with lupus nephritis. Nephrol Dial Transplant. Published online October 11, 2022. doi:10.1093/ndt/gfac286