Effective combination of corticosteroid and cyclosporine A for immunoglobulin A nephropathy with membranoproliferative glomerulonephritis features: a case report

Abstract

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide with heterogeneous histopathological phenotypes. Although IgAN with membranoproliferative glomerulonephritis (MPGN)-like features has been reported in children and adults, treatment strategies for this rare IgAN subtype have not been established. Here, we present the case of a 56-year-old man with no history of kidney disease who initially presented with nephrotic syndrome. Renal biopsy revealed MPGN-like features with a negative serological workup for secondary causes. Immunofluorescent staining was predominantly positive for IgA in the glomerular mesangial and capillary walls. Galactose-deficient IgA1 staining showed a distribution pattern similar to IgA staining. Electron microscopy revealed disorganized structural deposits in the mesangial and subendothelial regions. Based on clinical and histopathological findings, the patient was diagnosed with primary IgAN. The nephrotic syndrome resolved completely after six months of combined corticosteroids and cyclosporine A (CsA) therapy. Although corticosteroids and CsA were tapered off, hematuria and proteinuria remained in complete remission for years of follow-up. This case demonstrates the importance of recognizing IgAN with MPGN-like features as a histopathological subtype that may benefit from intensive immunosuppressive therapy.

Keywords: Corticosteroids; Cyclosporine A; Galactose-deficient IgA1; IgA nephropathy; Membranoproliferative glomerulonephritis; Nephrotic syndrome.

Fig. 1

Histopathological findings of renal biopsy. a Light microscopy showed moderate diffuse mesangial and endocapillary proliferation with occasional lobular structures (circle) (periodic acid-Schiff stain, × 200). b The capillary walls showed thickness forming features of double contour (arrow heads) (periodic acid methenamine silver stain, × 400)

Fig. 2

Immunofluorescence study. Immunofluorescence staining was positive for immunoglobulin (IgA), predominantly in the mesangium and capillary walls. IgG was positive and C3 was weakly positive in the capillary walls (fluorescein isothiocyanate anti-human IgG, IgA, IgM, C3, and C1q × 400)

Fig. 3

Immunofluorescence study. a An immunofluorescence study of the immunoglobulin A (IgA) subtype (fluorescein isothiocyanate [FITC] anti-human IgA1, IgA2, × 400). IgA1 was predominantly positive in the mesangium and capillary walls. b An immunofluorescence study of the light chain (FITC anti-human kappa, lambda, × 400). Lambda was predominantly positive in the mesangium and capillary walls. c An immunofluorescence study using KM55, specifically recognizing galactose-deficient IgA (Gd-IgA). Gd-IgA1, detected by the KM55 mAb, exhibited localization patterns similar to IgA

Fig. 4

Electron microscopy findings. a Electron microscopic examination shows localization of immune-type electron-dense deposits (circle) in the mesangial region (× 6,000). b The electron-dense deposits were disorganized structures (× 60,000). c Ultrastructural examination of this capillary wall showed subendothelial deposits (× 60,000). d The white arrow indicated circumferential mesangial interposition in the glomerular basement membrane (× 6,000). En endothelial cell, Mes mesangial cell

Fig. 5

Patient’s clinical course. The figure shows a comprehensive picture of the patient’s clinical course, tracking urinary total protein (UTP) (g/gCr), serum albumin (Alb) level (g/dL), urine red blood cell count (gray column, scale; 0–4), and treatment regimen. At the initial presentation, the patient presented with marked proteinuria and hypoalbuminemia. Simultaneously, microscopic hematuria was intermittently positive. A renal biopsy (RBx) was performed 2 days after admission. High-dose prednisolone (PSL) was started, including pulse therapy, and the UTP levels gradually decreased. Cyclosporine A (CsA) therapy was subsequently initiated, leading to a gradual reduction in PSL dosage and further improvement in UTP levels. Nine months after admission, complete remission was observed