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

BackgroundA 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.MethodsWe 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.ResultsMost 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.ConclusionsWe identified patients with proteinuria ≤500 mg/g who had lupus nephritis, with the majority ranging from Class III 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.