Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival

Abstract

Background. A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health (NIH) activity and chronicity indices have been proposed to classify LN lesions but should be validated by future studies. Aims of this study: i) to detect the histological features associated with the development of Kidney Function Impairment (KFI); ii) to identify the best clinical-histological model to predict KFI at time of kidney biopsy. Methods. LN patients with kidney biopsy containing >10 glomeruli per specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards model were used to investigate whether activity and chronicity indices could predict KFI development. Results. Among 203 LN participants followed for 14 years, correlations were found between activity index and its components and clinical-laboratory signs of active LN at baseline. Chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indexes. At multivariate analysis glomerular sclerosis (OR:3.0478, CI:1.173-7.91, P=0.022) and fibrous crescents (OR:6.8352, CI:3.218-14.519, P<0.001) associated with either moderate/severe tubular atrophy (OR:3.1697, CI:1.042-9.643, P=0.0421), or with interstitial fibrosis (OR:2.361, CI:1.047-5.322, P=0.0383) predicted KFI. Considering both clinical and histological features, serum creatinine (OR:1.677; 1.311-2.145; P<0.001), arterial hypertension (OR:4.641, CI: 1.902-11.324, P<0.001), glomerular sclerosis (OR:2.123, CI:1.001-4.503, P=0.049), and fibrous crescents (OR:5.182, CI: 2.433-11.037, P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. Conclusions. Chronicity index and its components, but not activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.

A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

“…Thus, the 2018 revision of the ISN/RPS classification proposed that the designation of activity/chronicity by the terms A, A/C, and C is too broad and should be replaced by a semiquantitative assessment of histological lesions in the form of a modified NIH activity and chronicity index [ 21 , 48 ]. Nonetheless, despite an overall improvement to the previous approach, the NIH indices should be further validated in independent cohorts and should be implemented in the design of clinical trials [ 49 ]. In addition, as these modified scores do not incorporate all the histologic lesions encountered in patients with SLE, the biopsy report should at least describe the presence of additional lesions as these might be related to outcome and might potentially be a treatment modifier [ 21 ].…”

Predictors of increase in chronicity index and of kidney function impairment at repeat biopsy in lupus nephritis

“…Out of 203 adults with biopsy-proven LN described elsewhere, 11 we selected for this study the subjects who received a second KB. The reasons for repeated biopsy were: proteinuric flare, nephritic flare and protocol biopsy.…”

“…on August 21, 2022 fibrosis were independent predictors of kidney function impairment (KFI) at multivariate analysis. 11 Studies on repeated KB are few and report contrasting results. Some studies were based on protocol biopsies, [12][13][14][15][16] while other reports included biopsies done for clinical reasons.…”

“…2 3 Further studies found that activity index may indicate whether a treatment should be aggressive or not while chronicity index seemed to be associated with poor prognosis. [4][5][6][7][8][9][10][11] Kojo et al 5 found that extracapillary proliferation, glomerular sclerosis and fibrous crescents were independent predictors of poor kidney outcome, while Hsieh et al 6 reported that tubulointerstitial inflammation and fibrosis, but not glomerular injury, were correlated with the risk of end stage kidney disease. In a retrospective study on 203 patients with LN followed for a median period of 14 years, interstitial inflammation was the only component of activity index associated with decrease in creatinine clearance.…”

“…Among the components of chronicity index, glomerular sclerosis, fibrous crescents and interstitial fibrosis were independent predictors of kidney function impairment (KFI) at multivariate analysis. 11 …”