Background Lupus nephritis (LN) is a complication of systemic lupus erythematosus that requires renal biopsy (RB). Proliferative classes III, IV-S, IV-G have especial clinical and pathological characteristics. Aim To determine the association between pathological features in RB with serum creatinine and urine protein levels. Material and Methods We analyzed 186 RB performed in adults aged 18 to 73 years, from a renal pathology reference center. Histopathological variables such as class and subclass of proliferative LN, endocapillary and extracapillary proliferation, activity and chronicity indexes, and vascular sclerosis were correlated with serum creatinine and urine protein levels, at the time of diagnosis. Results As compared with LN III, all the morphological and laboratory values were significantly more deteriorated in LN IV, with special focus on vascular sclerosis. Serum creatinine was the only variable that significantly differentiated LN IV-S from LN IV-G. Proteinuria was non-significantly higher in LN IV-G compared to LN IV-S. However, the difference became significant when proteinuria was compared between LN IV-G and LN III. Conclusions The significant difference in serum creatinine between LN IV-S and LN IV-G supports the concept that they are different subclasses. Proteinuria is a variable that differentiates classes III from IV-G, being significantly higher in the second. Severe arteriosclerosis is a constant and significant finding that differentiates LN III from LN IV. Thus, we propose its usefulness for distinguishing LN classes, and eventually, to be considered in the chronicity index.