ANCA-Associated Necrotizing Glomerulonephritis Overlapping with Mesangial Proliferative Lupus Nephritis Refractory to Plasmapheresis, Steroid Pulse Therapy, and a Combination of Mycophenolate Mofetil and Rituximab

Abstract

Necrotizing glomerulonephritis (GN) associated with antineutrophil cytoplasmic antibody (ANCA) has been increasingly recognized in the context of class III or IV lupus nephritis (LN), hereafter designated as ANCA-associated necrotizing LN. While this subset of GN appears to portend an unfavorable renal outcome, it is not clear whether it represents a distinct entity and benefits from a more aggressive therapy. We report a 78-year-old woman who presented with rapidly progressive GN and was found to have a double-stranded DNA (dsDNA) antibody, hypocomplementemia, antiphospholipid antibody, and strongly positive myeloperoxidase antibody. Renal pathology showed necrotizing and crescentic GN on a background of mesangial proliferative GN. Her kidney disease did not improve despite the treatment with plasmapheresis, three doses of methylprednisolone pulse therapy followed by prednisone at 1 mg/kg/day, rituximab, and mycophenolate mofetil. This case not only reinforces the notion that ANCA-associated necrotizing LN is associated with high dsDNA antibody, hypocomplementemia, and worse renal outcome but also adds new insight into the full spectrum of this emerging disease entity by demonstrating that the concurrence of ANCA-associated vasculitis is not specific for class III or IV LN but can also be seen on a background of class II LN.

Analysis of glucocorticoid receptor and microRNAs expression in pathological renal tissues

“…Glucocorticoids receptors (GRs) belong to the family of steroid hormone receptors and they are found in a number of different cell types in the human kidney, including glomerulus cells, podocytes, epithelial cells and endothelial cells ( 1 , 2 ). Glucocorticoids (GCs) are commonly used to treat proteinuric glomerular diseases, such as membranoproliferative glomerulonephritis ( 3 ), membranous nephropathy ( 4 ), IgA nephropathy, crescentic glomerulonephritis ( 5 ) and antiglomerular basement membrane disease ( 6 ). In general, GCs remain the cornerstone of treatment for a number of inflammatory such as lupus nephritis (LN) ( 7 , 8 ) as well as for non-inflammatory renal diseases such as the Minimal Change Nephropathy (MCD) ( 7 , 9 ).…”

Clinicopathologic characteristics and outcomes of lupus nephritis with positive antineutrophil cytoplasmic antibody

“…The extensive necrotic and pauci-immune glomerular inflammation observed in some patients with Class IV-S LN may be associated with ANCAs [5,6,[8][9][10]. Some studies have reported an association between this histopathologic phenotype and ANCA positivity [5,6,8,9,[11][12][13], but others found no association.…”

Role of the glucocorticoid receptor in glomerular disease

“…GR is widely expressed in the human kidney, including in the glomerulus (30), and GCs are used clinically in a variety of proteinuric glomerular diseases, including membranoproliferative glomerulonephritis (11), membranous nephropathy (2), IgA nephropathy (12), crescentic glomerulonephritis of many etiologies (14,20,23), and antiglomerular basement membrane disease (29). However, it is from the treatment of nephrotic syndrome (NS), both in pediatric and adult patients, for which GCs are a mainstay of therapy, that most of the current knowledge about GC effects on glomeruli and clinical practice patterns have evolved.…”