Evaluating Chronicity Scores for Outcomes in Patients With Lupus Nephritis

Introduction The aim of this study was to evaluate the prognostic value of the Mayo Clinic Chronicity Score (MCCS) compared with the National Institutes of Health (NIH) Chronicity Index (NIH-CI) in lupus nephritis (LN). Methods We conducted a retrospective cohort study of 307 patients with biopsy-proven LN evaluated at Mayo Clinic (1992–2023). Chronic histologic injury was graded using the NIH-CI and MCCS. Outcomes were proteinuria remission < 500 mg/d (PR500), complete renal response (CRR), end-stage kidney disease (ESKD), and all-cause mortality. Sex-stratified, age-adjusted Cox models were used. Prognostic performance was evaluated using change in Harrell's C-index (ΔC over a clinical model) and decision-curve analysis was used to assess clinical utility for 5-year ESKD. Subgroup analyses were used to test for effect modification by baseline estimated glomerular filtration rate (eGFR) (< 60 vs. ≥ 60 ml/min per 1.73 m 2 ) and histologic class (proliferative vs. nonproliferative). Results Higher NIH-CI and MCCS scores were associated with lower likelihood of PR500 and CRR (hazard ratio [HR]: 0.75 for both) and greater risk of ESKD (HR: 1.40 for NIH-CI; 1.33 for MCCS). Adding either score to a clinical model improved discrimination for PR500 (C-index: 0.65 to 0.71), CRR (0.64 to 0.71), and ESKD (0.81 to 0.85), but not mortality (ΔC = 0.00). Decision-curve analysis showed similar net benefits for NIH-CI and MCCS. Interstitial fibrosis (IF) and tubular atrophy (TA) (IF/TA) were the only components independently predictive of renal outcomes. Our findings support applicability of both scores in nonproliferative LN and in patients with reduced baseline kidney function. Conclusion The MCCS and NIH-CI provide comparable and additive prognostic information in LN. MCCS captured the chronic lesions most strongly associated with renal outcomes, with IF/TA as the principal determinant of prognosis.