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.