Current systemic lupus erythematosus (SLE) guidelines recommend performing a kidney biopsy in patients with a urine protein-to-creatinine ratio (UPCR) of 0.5 g/g or more. For higher-risk patients, the proteinuria threshold for biopsy may need to be lowered for early detection of lupus nephritis, according to new research.
In a study of 151 patients with SLE and low-grade proteinuria (new onset UPCR of 0.2 to less than 0.5 g/g) in the Einstein Rheumatic Disease Registry, 76 (50%) progressed to UPCR of 0.5 g/g or more within a median 1.2 years. Of the 76 progressors, 46 patients were fast progressors who developed overt proteinuria within 2 years. Of the 20 patients who underwent a clinically indicated biopsy in those first 2 years, 16 had active lupus nephritis that could be treated.
“The current study confirms that over half of SLE patients with low-grade proteinuria progress to overt proteinuria, supporting the role for early biopsy to diagnose lupus nephritis, even in the absence of hematuria,” Anna Broder, MD, MS, of Hackensack University Medical Center in New Jersey, and colleagues wrote in the Clinical Journal of the American Society of Nephrology. Data on active urinary sediment were not routinely available.
Low complement 3 or 4 levels and shorter duration of SLE at the onset of low-grade proteinuria were significantly associated with progression to overt proteinuria. Low complement had the highest sensitivity and specificity for overt proteinuria “underscoring the need to monitor complement level closely in the presence of low-grade proteinuria to identify patients in the early stages of lupus nephritis.” Other possible risk factors included hypertension, diabetes mellitus, age 29 years or younger, and hematuria.
Currently, clinicians do not have reliable clinical markers to predict which SLE patients with low-grade proteinuria should undergo biopsy. A deeper understanding of the molecular drivers of the disease process is needed to develop biomarkers of early lupus nephritis, according to Dr Broder’s team.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Wang S, Spielman A, Ginsberg M, et al. Short- and long-term progression of kidney involvement in systemic lupus erythematosus patients with low-grade proteinuria. Clin J Am Soc Nephrol. Published online July 26, 2022. doi:10.2215/CJN.01280122