A Case of Lupus Podocytopathy in Transition to Membranous Lupus Nephritis Class V With Positive APOL-1 Gene

ABSTRACT

Introduction: Lupus podocytopathy (LP) is a glomerular lesion in systemic lupus erythematosus (SLE) patients characterized by diffuse epithelial cell foot process effacement (FPE) without immune complex deposition or with only mesangial immune complex deposition. In SLE, nephrotic syndrome in rare instances, appear as LP, mimicking minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS). Case Description 21-year-old African American female with a past medical history of eczema, kidney stone, COVID-19, facial rash admitted with persistent shortness of breath, lower extremity swelling with symptomatic anemia. Patient was noted to have nephrotic syndrome with positive serology for SLE and low complements. Renal biopsy showed lupus podocytopathy with features of collapsing glomerulopathy. The absence of endocapillary proliferation, presence of collapsing features, and lack of sub-endothelial immune complexes on electron microscopy (EM) are features consistent with LP with transition to Membranous lupus nephritis (LN) Class V. Patient was started on steroids, mycophenolate mofetil, and hydroxychloroquine. Voclosporin was added at one month follow-up given persistent nephrotic syndrome. Proteinuria improved significantly to 2 g in 4 weeks and prednisone taper was started. APOL1 gene assay revealed presence of G1, G2 risk alleles. Discussion(s) The prevalence of LP in LN biopsies is approximately 1% and is diagnosed based on clinical presentation of nephrotic syndrome with SLE and kidney biopsy findings of diffuse and severe FPE on EM, and absence of subendothelial or subepithelial immune deposits on EM. LP is further subclassified as MCD or FSGS subtypes. The MCD forms respond well to treatment with glucocorticoids as induction therapy, adding a nonglucocorticoid immunosuppressive agent only to treat or, in some cases, to avoid relapses. On the other hand, the FSGS forms with collapsing lesions have worse outcomes, progressing to end-stage renal disease in more than 50% of the cases. LP FSGS subtypes are less steroid-responsive and may benefit from initial induction treatment with glucocorticoids and another agent, such as calcineurin inhibitors. APOL1 genotyping of African American patients with SLE might help identify patients at risk for collapsing glomerulopathy, an entity with poor prognosis and resistance to treatment.