Background: Lupus nephritis (LN) is a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE), resulting in end-stage kidney disease in 20% of cases. Despite optimal treatment, only 30%–40% of patients with LN achieve a complete renal response at 1 year. LN diagnosis, classification, and treatment rely on kidney biopsy. Kidney biopsies are essential for diagnosing and classifying LN in SLE patients with proteinuria, as proteinuria alone cannot distinguish between treatable inflammation and chronic kidney damage, nor can it differentiate between the International Society of Nephrology (ISN) LN classes. Although the modified NIH activity and chronicity indices (mAI and mCI), introduced by the 2018 ISN/RPS guidelines, show potential in stratifying patients, they lack clinical validation and defined thresholds for identifying high-risk patients.

Objectives: The aim of this study is to evaluate the prognostic value of the mAI, mCI, and other clinicopathological factors in a cohort of LN patients who underwent kidney biopsy. By assessing these variables, we aim to improve the stratification of patients and enhance the predictive accuracy for long-term renal outcomes.

Methods: Patients who underwent kidney biopsies for diagnostic purpose between January 2018 and June 2024, were retrospectively enrolled in the study. Glomerular and interstitial lesions in LN were quantified using a 0-3 scoring system, based on the revised 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for LN and the modified NIH scoring system, as assessed by a renal pathologist. Additionally, the Total Renal Chronicity Score (TRCS), a score based on a consensus report for glomerular diseases, was measured. Renal endpoints included achievement of complete renal response (CRR) at 1 year (defined as proteinuria <0.5g/day, withdrawal of glucocorticoid therapy, estimated glomerular filtration rate (eGFR) >90% of baseline). A combined negative outcome (CO) at 1 and 2 years was also assessed, defined by the occurrence of end-stage kidney disease (ESKD), a 25% decrease from the baseline eGFR or an increase in proteinuria of more than 50% from baseline. Statistical correlations were analyzed using t-tests and Spearman’s correlation coefficients.

Results: 35 LN patients were included: 80% with proliferative LN (71.4% with ISN III or IV, 8.57% III+V or IV+V) 9% with pure membranous LN (ISN V) and 11% with mesangioproliferative LN (ISN II). The average mAI and mCI indices were 5.46 ± 3.6 and 2.71 ± 1.4, respectively. CRR was achieved by 65.7% of patients at 1 year, 31.4% met CO at 1 year and 34.3% at 2 years. The mAI was not significantly associated with any of the selected outcomes and could not predict EGFR variation at any point in the disease course. At univariate analysis, mCI correlated with eGFR absolute value at 6 months (p = 0.04) and 1 year (p=0.02). There was also an association between mCI and no CRR at 1 year(p=0.001); however, this association didn’t persist at multivariate analysis. When categorized using TRCS thresholds, tubular atrophy emerged as the most promising prognostic individual variable at both univariate and multivariate testing. The TRCS showed similar performance to the mCI in the prediction of CRR at 1 year and eGFR at 6 months (p=0.01) and 1 year (p < 0.01). Furthermore, there was a strong association between TRCS and eGFR value at the time of biopsy (p=0.046) and at 2 years (p = 0.02).

Conclusion: Our study showed the limitations of mAI and mCI as reliable prognostic tools. Moreover, our results highlighted the importance of chronic tubulo-interstitial lesions scored by TRCS, as prognosticators of LN. The performance of the TRCS raises questions on the impact of the individual sub-items of the mCI and on their scoring thresholds. Our data suggest the need to refine chronicity scoring systems, aiming to enhance the accuracy of prognosis and improve clinical decision-making in lupus nephritis.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.