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Austin et al, when formulating the National Institutes of Health (NIH) chronicity and activity indexes (AI/CI) for Lupus Nephritis (LN), related the CI to poor prognosis; not so the activity index (AI). In the 2018 revision of the ISN/RNP classification, the "glomerular sclerosis" (GS) sub-score of the CI included both global and focal lesions, while "fibrous crescents" is defined as a fibrotic lesion, result of the evolution of originally active lesions. In this work we describe how cellular crescents evolve to focal sclerotic lesions using sequential re-biopsies.
Our cohort included 120 patients with class IV or IV+V lupus nephritis who were treated at the Nephrology Unit at Fernandez Hospital in Buenos Aires from 2005 up to December 2022. All patients were biopsied initially (Bx1) for diagnosis and after 42 months of immunosuppression, having achieved a sustained complete clinical response of at least 12 months (Bx3); 81 (67,5%) patients also had an intermediate biopsy (Bx2) between Bx1 and Bx3.
The Revised International Society of Nephology /Renal Pathology Society 2018 LN classification and the revised NIH activity and chronicity indexes were used to describe the biopsies.
The presence of cellular and fibrous crescents (CR)and glomerulosclerosis (focal +global) was determined in all the biopsies. The relationship between these two chronicity components throughout the treatment (assessed by re-biopsies), as well as the relevance of their presence in patients with complete histological remission in Bx3 was studied.
All data are expressed as mean (SD) unless otherwise indicated. Simple and multiple linear regression analyses were carried-out to assess the association between variables. A p value <0.05 was considered statistically significant.
Table 1: Tipe of crescentes in BX1, Bx2 and Bx3
Table 2: Gomerular sclerosis and fibrous crescents in Bx1, Bx2 and Bx3 (mean ±SD) & GS or fibrous CR in Bx1 compared to Bx3
Of the 99 (82%) patients with crescents in Bx1, only 9 (7.5%) showed fibrous crescents in Bx3 and no patient had cellular crescents in this third biopsy. The persistence of fibrous CR in the 9 patients was not related to different time elapsed between biopsies 1 and 3 nor was it related to the % of cellular CR in the initial sample since all of them showed CR between 25 to 50% and the 5 cases with ˃50% of cellular CR in Bx1 didn’t t show fibrous CR in their Bx3. The time gone by between biopsy 1 and 3 in the group with persistence of fibrous crescents in Bx3 was 42,4 months (range 30-68 months) and in the group without crescents (all turned into GS) was 43,6 months (range 31- 65months). The evolution described exposed an inverse relationship between the increase in GS and the near disappearance of the crescents
In patients with a complete clinical response, the near disappearance of crescents seems to be very common. We certainly expect the disappearance of cellular crescents, but would have assumed that the cellular crescents would still be represented over time by fibrous crescents. The absence of fibrous crescents in patients who had crescents in Bx1, coupled with the increase in GS in these patients suggests that distinguishing between fibrous crescents and GS is difficult the older the lesion becomes. We therefore suggest that the CI may not need to be divided into GS and fibrous crescents, but chronic glomerular damage could be expressed by the % of glomeruli with any sclerosis and graded by the average extent of GS in the glomeruli found on the biopsy.