Silent but Severe: Atypical Presentation of Class IV Lupus Nephritis with No Overt Proteinuria

Introduction: Current guidelines recommend kidney biopsy in systemic lupus erythematosus (SLE) patients with proteinuria >500 mg/24 hours or unexplained renal dysfunction. It is commonly assumed that in the absence of significant proteinuria, kidney disease is unlikely to be severe. We present a case of a 35-year-old woman with SLE and minimal proteinuria who was found to have class IV lupus nephritis (LN). Case Description: A 35-year-old female with known SLE presented with albumin-to-creatinine ratio of 68 mg/g, microscopic hematuria, low complement levels, and mildly elevated anti-dsDNA antibodies. She had no previous renal disease, and her serum creatinine was 0.5 mg/dL. Given clinical concern for renal involvement, a biopsy was performed, which revealed diffuse mesangial hypercellularity and segmental duplication of glomerular basement membranes consistent with diffuse proliferative LN. Immunofluorescence showed global granular staining for IgG, IgA, IgM, C1q, C3, kappa, and lambda (all 4+), confirming class IV LN. The patient remained on hydroxychloroquine 200 mg daily and prednisone 10 mg daily, and mycophenolate mofetil was initiated for LN. Discussion: Class IV LN generally presents with marked proteinuria and/or impaired renal function. Current American College of Rheumatology (ACR) guidelines recommend biopsy in cases of significant proteinuria or unexplained renal impairment. However, some patients demonstrate advanced histologic disease despite minor urinary abnormalities. This clinical phenotype is not adequately addressed in the existing guidelines. While hypocomplementemia and elevated anti-dsDNA titers suggest disease activity, their predictive value for LN is not well understood. This case underscores the limitations of current diagnostic criteria for LN, particularly in atypical presentations. Despite minimal proteinuria and normal renal function, the patient had advanced diffuse proliferative LN, emphasizing the need for more nuanced clinical judgment. Furthermore, the absence of overt proteinuria complicates both disease monitoring and clinical trial eligibility, indicating a need for updated guidelines to better capture these silent but severe presentations.