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

Abstract

Background and objectivesLupus nephritis remains a common cause of morbidity and mortality in systemic lupus erythematosus (SLE). Current guidelines recommend performing a kidney biopsy at urine protein-to-creatinine ratio (UPCR) of ≥0.5 g/g. However, cross-sectional studies reported a high prevalence of active histological lupus nephritis lesions, and even chronic irreversible scarring, in patients with low-grade proteinuria. This study was initiated to assess disease progression in SLE patients with low-grade proteinuria to identify risk factors for progression to overt proteinuria suggestive of clinical lupus nephritis. Design, setting, participants, & measurementsSLE patients with incident UPCR ≥ 0.2 and <0.5 g/g without known lupus nephritis were identified from the Einstein Rheumatic Disease Registry. Patients who developed a random UPCR of ≥ 0.5 g/g with or without biopsy during the follow-up period were defined as "progressors". Patients who progressed to UPCR>0.5 g/g within two years from developing UPCR≥ 0.2 &<0.5 g/g were defined as "fast progressors", a subgroup expected to benefit most from early biopsies and therapeutic interventions. ResultsAmong 151 eligible SLE patients with low-grade proteinuria at study entry, 76 (50%) progressed to UPCR≥0.5 g/g of which 44 underwent a clinically indicated biopsy. The median (IQR) time from UPCR≥ 0.2 & <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 had 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. ConclusionsIn this longitudinal cohort of SLE patients with low-grade proteinuria at study entry, over half progressed to UPCR>0.5 g/g in a short time period supporting the role of early biopsy to diagnose and treat lupus nephritis.

Kidney Biopsy in Management of Lupus Nephritis: A Case-Based Narrative Review

“…A significant inflammatory disease may be observed in patients with proteinuria below this threshold and even in patients without any evidence of clinical involvement. 16 , 26 , 27 , 28 , 29 In most of these series, the additional finding of low complement C3 and/or positive anti-dsDNA antibodies was associated with a higher degree of inflammatory activity in the kidney biopsy or a higher risk of progressive disease. 26 , 27 , 28 , 29 …”

“… 16 , 26 , 27 , 28 , 29 In most of these series, the additional finding of low complement C3 and/or positive anti-dsDNA antibodies was associated with a higher degree of inflammatory activity in the kidney biopsy or a higher risk of progressive disease. 26 , 27 , 28 , 29 …”

Insights into future management of lupus nephritis

“…[eGFR]) should have a kidney biopsy performed (16,17). More recent data, which will be reviewed in this publication, suggest that a broader indication for kidney biopsy should be recommended, such as the presence of glomerular hematuria accompanied by any degree of proteinuria (18)(19)(20). The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification represents the gold standard for assessment of kidney biopsies in LN, affirming the diagnosis of LN and guiding treatment decisions (16,17,21).…”