FRI0188 THE CLINICOPATHOLOGICAL SIGNIFICANCE OF MODIFIED NATIONAL INSTITUTES OF HEALTH ACTIVITY AND CHRONICITY SCORING SYSTEM IN LUPUS NEPHRITIS; A MULTICENTER RETROSPECTIVE STUDY

Abstract

Background:The revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) Classification of lupus nephritis (LN) 2018 defined a modified National Institutes of Health activity and chronicity scoring system for all LN classes [1]. As this was not arrived at by an evidence-based approach, its clinicopathological significance including prognostic value should be validated [1]. Furthermore, though the activity index included wire-loop lesion and hyaline deposits (WL), we previously demonstrated that WL was associated with serological immune abnormality, but not renal prognosis [2].Objectives:We conducted this study to clarify the relationships of modified activity score (AS) and chronicity score (CS) to clinical parameters at the time of renal biopsy and renal and life prognoses, and also to investigate the impact of AS without WL.Methods:We enrolled 138 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2019. We measured clinical findings at the time of renal biopsy, and determined the presence of comorbidities. We also measured serum creatinine and estimated glomerular filtration rate (eGFR) at the last patient visit, and recorded medications prescribed for LN. Renal biopsy findings were classified by the modified ISN/RPS classification 2018 including AS and CS for all LN classes. On stepwise multivariate analysis, we applied the variables with significant differences in univariate comparisons. The primary endpoint was chronic kidney disease (CKD; eGFR <60 ml/min/1.73m2) and/or death.Results:Of 138 patients (116 females; median 39 years old), class I, II, III, IV, and V included 2 (1.4%), 13 (9.4%), 43 (31.2%), 69 (50.0%), and 11 (8.0%), respectively. Median AS, AS without WL (AS-WL), and CS were 4, 3, and 2, respectively. AS ≥5 group (61 patients, 44.2%) had higher proteinuria, hematuria and serum anti-ds DNA antibodies levels and lower serum total protein (TP) and C3 levels than AS <5 group. CS ≥3 group (58 patients, 42%) had higher age, proteinuria, serum C3 levels, and frequency of hypertension (HT) and lower eGFR and serum anti-ds DNA antibodies and IgG levels than CS<3 group. Multiple regression analysis revealed significant associations between AS and hematuria, TP and C3 (β=0.312, -0.281, -0.213;p<0.001, 0.001, 0.009), and between CS and age (β=0.300;p=0.010). Next, patients who achieved the primary endpoint had higher age, frequencies of HT and hyperlipidemia and lower eGFR, serum TP and IgG levels than patients who did not. Observation period (median 36 vs 47 months,p=0.696) and medications for LN did not differ between these groups. Cox regression analysis revealed significant associations of prognosis with eGFR and TP clinically (β=0.955, 3.349;p=0.025, 0.008), and with CS pathologically (β=1.231,p=0.028). Neither AS nor AS-WL was included in the prognostic factors. Kaplan-Meier method with log-rank tests showed a significant difference in cumulative rate of CKD and/or death between CS ≥3 and CS <3 groups (p=0.049).Conclusion:AS and CS were related to different clinical parameters at the time of renal biopsy. CS was associated with renal and life prognoses, while neither AS nor AS-WL was. These results revealed that these scores have different clinicopathological significance in LN.