First Successful Treatment of a Patient with a Primary Immune Complex-Membranoproliferative Glomerulonephritis with Iptacopan: A Case Report

Abstract

Introduction: Nowadays, there is insufficient evidence for the recommendation of management patients with a primary membranoproliferative glomerulonephritis (MPGN). A better understanding of the pathogenesis has led to the reclassification of primary MPGN and distinction into the two main entities of either primary immune complex-MPGN or C3 glomerulopathy. Both entities share overlapping pathophysiological features with complement alternative pathway (AP) dysregulation. Iptacopan is an oral inhibitor of the complement factor B that effectively blocks the complement AP.

Case presentation: We report the first successful treatment of a 47-year-old man suffering from a primary immune complex-MPGN with iptacopan. So far established immunosuppressive therapies with prednisone and mycophenolate mofetil failed to control the current flare of the disease, mainly presenting with impaired kidney function and proteinuria within the nephrotic range. However, 3 months after starting the treatment with iptacopan urine protein-creatinine ratio decreased impressively to a level of 100-150 mg/mmol. Thereafter, low-level proteinuria and kidney function remained stable during follow-up. Do date, the treatment with iptacopan is continued as a monotherapy and is well tolerated.

Conclusion: To the best of our knowledge, this is the first case report which suggests that iptacopan may be an interesting treatment option for primary immune complex-MPGN.

Keywords: Alternative complement pathway; Complement factor B inhibitor; Iptacopan; Membranoproliferative glomerulonephritis; Primary immune complex-associated.

Fig. 1.

Targeting of the complement system by different complement inhibitors. Adapted with courtesy of Novartis.

Fig. 2.

Course of the successful treatment of a 47-year-old man suffering from a biopsy-confirmed primary immune complex-MPGN with the complement factor B inhibitor iptacopan. For the dosage of medication, refer to the text. MPGN, membranoproliferative glomerulonephritis; UPCR, urine protein-creatinine ratio; RAS, renin-angiotensin-system.

Fig. 3.

Histopathological findings. a By light microscopy, the glomeruli showed a prominent lobular architecture with increased mesangial and intracapillary cellularity (black arrow). The peripheral glomerular basement membranes focally showed double contours (red arrow). There were also several segmental scleroses (white arrow), PAS-staining, ×200. By immunofluorescence, there was diffuse global granular deposition of C3 (b) and IgG (c) (immunofluorescence, ×400). d By electron microscopy there was intensive remodeling of peripheral glomerular basement membranes with presence of intramembranous, subepithelial and subendothelial deposits (black arrow). There were also mesangial deposits (white arrow). Further, there was extensive loss of foot processes (red arrow) (electron microscopy, ×2800).