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

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.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.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.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.