Long-term outcomes and treatments for proliferative lupus nephritis with low-level proteinuria: a multicentre retrospective study in Japan.

Objective: The long-term prognosis of patients with proliferative lupus nephritis (class III/IV) and low-level proteinuria remains unclear. Moreover, as some clinical trials have excluded them, the efficacy of some immunosuppressants for this subset of patients has not been strictly confirmed. In this study, we aimed to investigate the renal and overall survival and treatments.

Methods: We conducted a retrospective study including 137 Japanese patients with biopsy-confirmed proliferative lupus nephritis from 11 hospitals. Based on previous reports, proteinuria of ≤1 g/gCr was defined as low-level proteinuria. The endpoints were kidney failure (KF) or death.

Results: Compared with the high-level proteinuria group (proteinuria >1 g/gCr), the low-level proteinuria group (62 cases (45.3%)) had better baseline renal functions and histology and included more patients initially treated with glucocorticoids (GCs) alone (26 (41.9%) vs 18 (24.0%), p=0.04). Maintenance therapy was similar between groups. After a median of 93 months, the low-level proteinuria group had a lower incidence of KF or death than the high-level proteinuria group (3 (4.8%) vs 22 (29.3%), p<0.001). Kaplan-Meier analysis revealed a significant difference in the incidence of these outcomes between groups. Similarly, patients with low-level proteinuria initially treated with GCs alone exhibited a better long-term prognosis than those with high-level proteinuria. Multivariate Cox regression analyses revealed that KF or death was associated with high levels of proteinuria but not with GCs alone for the initial treatment.

Conclusions: Patients with low-level proteinuria have a favourable long-term prognosis and are treated with less initial immunosuppressant use, suggesting a distinct clinical subgroup of proliferative lupus nephritis. Renal biopsy in the early phase with low-level proteinuria may lead to early diagnosis and treatment. A treatment strategy tailored to patients with low-level proteinuria may be required.