Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Abstract

Background and objectives: Lupus nephritis remains a common cause of morbidity and mortality in systemic lupus erythematosus (SLE). Current guidelines recommend performing a kidney biopsy at a urine protein-creatinine ratio of ≥0.5 g/g. However, cross-sectional studies reported a high prevalence of active histologic lupus nephritis lesions, and even chronic irreversible scarring, in patients with low-grade proteinuria. This study was initiated to assess disease progression in patients with SLE and low-grade proteinuria to identify risk factors for progression to overt proteinuria suggestive of clinical lupus nephritis.

Design, setting, participants, & measurements: Patients with SLE who had an incident urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g without known lupus nephritis were identified from the Einstein Rheumatic Disease Registry. Patients who developed a random urinary protein-creatinine ratio of ≥0.5 g/g with or without biopsy during the follow-up period were defined as "progressors." Patients who progressed to a urinary protein-creatinine ratio of ≥0.5 g/g within 2 years of developing a urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g were defined as "fast progressors," a subgroup expected to benefit most from early biopsies and therapeutic interventions.

Results: Among 151 eligible patients with SLE and low-grade proteinuria at study entry, 76 (50%) progressed to a urinary protein-creatinine ratio of ≥0.5 g/g, of which 44 underwent a clinically indicated biopsy. The median (interquartile range) time from a urinary protein-creatinine ratio of ≥0.2 and <0.5 g/g to progression was 1.2 (0.3-3.0) years. Of the 20 biopsies performed in the first 2 years, 16 specimens showed active, treatable lupus nephritis. Low complement and shorter SLE duration at low-grade proteinuria onset were associated with progression to overt proteinuria across different analyses. Other associated factors included hypertension, diabetes mellitus, younger age, and the presence of hematuria.

Conclusions: In this longitudinal cohort of patients with SLE and low-grade proteinuria at study entry, over half progressed to a urinary protein-creatinine ratio of ≥0.5 g/g in a short time period.

Keywords: proteinuria; systemic lupus erythematosus.