Association of low-grade proteinuria with changes of lupus nephritis in kidney biopsy in SLE patients

Background: A kidney biopsy is essential for definitive histopathological diagnosis in lupus nephritis, informing therapeutic strategies. Current guidelines (ACR and EULAR/ERA-EDTA) do not include a kidney biopsy for patients with isolated proteinuria of less than 500 mg/g. We explored the histopathologic findings in patients with SLE with proteinuria <= 500 mg/g. Methods: We conducted a retrospective review of 27 biopsies of lupus patients with proteinuria <= 500 mg/g who underwent a kidney biopsy at Johns Hopkins. Clinical and laboratory data were obtained from a review of the medical records. The study was approved by the Office of Human Subjects Research and Institutional Review Board. Results: Most individuals were females (93%) and African American (56%), with a mean age of 42.1 (12.4) years at the time of biopsy. Twelve individuals had no prior history of lupus nephritis. The average creatinine at the biopsy was 1.05 mg/dl, and UPCR was 0.27 grams/gram. Most patients (100%) were on hydroxychloroquine, 41% were on prednisone, and 33% were on mycophenolate mofetil. Kidney biopsies were most commonly performed based on extra-renal disease activity, new-onset or worsening proteinuria (88.9%) and worsening dsdNA levels (55.6%). At the time of biopsy, 55.6% of patients presented with extrarenal lupus, most commonly arthritis or arthralgias and mucosal ulcers. Of the 27 patients, 23 patients had evidence of lupus nephritis (85.1%), including class III (33%), V (30%), III/V (7%), class II (4%) and class I (11%). Nine patients had a UPCR of 200 mg/g or lower. Among these patients, 22% did not show signs of lupus nephritis in the kidney biopsy, 44% had class V LN, and 11% had class I and III LN. Kidney biopsy was well tolerated, with the majority (93%) not developing post-biopsy complications. Conclusions: We identified patients with proteinuria <= 500 mg/g who had lupus nephritis, with the majority ranging from Class I to V with only one class II. This study supports that normal or low UPCR <500 mg/g lacks the sensitivity to detect early lupus nephritis. Better biomarkers for the cutoff of biopsy are needed to improve kidney outcomes and trial design.