PODOCYTE INFOLDING GLOMERULOPATHY IN A SCHOOL-AGED INDIAN CHILD: A NOVEL CASE REPORT

Introduction:

Podocyte infolding glomerulopathy (PIG) is a rare glomerular disease characterized by unique infolding of podocyte cytoplasmic processes into the glomerular basement membrane. It was first described as a new disease entity in 2008 and is often associated with various autoimmune conditions. Patients often present with nephrotic syndrome; however, the pathogenesis and clinical implications are poorly understood due to limited literature. This case report aims to expand the understanding of PIG by presenting the first documented instance of PIG in a school-aged child from India. 

Methods:

Case:

A previously healthy 5-year-old boy presented with hypertension and generalized oedema for 10 days. Laboratory investigations revealed nephrotic-range proteinuria, microscopic hematuria, hypoalbuminemia with normal renal function. He was treated with prednisolone at 60 mg/m²/day but developed macroscopic hematuria in the third week and nephrotic-range proteinuria persisted. Additional tests for ASO, C3, C4, ANA, ANCA and renal ultrasound were normal. Kidney biopsy revealed 15 glomeruli all of which were enlarged with mesangial proliferation, two exhibited fibrocellular crescents. Immunofluorescence showed fine granular deposits of 1gG (1-2+), C3(1-2+), Fibrinogen (1-2+) along the peripheral capillary walls. On electron microscopy, there was diffuse podocyte foot process effacement, glomerular basement membrane (GBM) was mildly thickened with focal duplication subepithelial deposits composed of ring-like microtubules (mean diameter: 66.5 nm) (Figure). No electron dense deposits were identified. A diagnosis of PIG was given.

Results:

Child received 3 methylprednisolone pulses followed by oral prednisolone and ACE inhibitor was added for hypertension and proteinuria. Tacrolimus (0.15 mg/kg/day) was initiated after receiving the biopsy report. Four weeks post Tacrolimus initiation, proteinuria has reduced to 2+ with resolution of hematuria and edema.

Discussion:

Podocyte infolding glomerulopathy is a rare renal disorder with most cases reported from East Asia, particularly Japan. The disease is often associated with autoimmune conditions, such as systemic lupus erythematosus (SLE) and membranous nephropathy. However, it can also occur independently or in association with other conditions like hepatitis B and malignancies. The pathogenesis of PIG remains poorly understood, though recent studies suggest a potential role for INF2 gene mutations but whole exome sequencing in this case did not reveal any significant pathogenic variants. The standard approach typically involves immunosuppressive therapy. In many cases, including ours, combining corticosteroids with calcineurin inhibitors (CNIs) has been effective​. However, some patients exhibit resistance to these therapies, necessitating individualized treatment strategies and further exploration of alternative options.

Conclusions:

This case is the first documented instance of Podocyte Infolding Glomerulopathy (PIG) in a pediatric patient from India emphasizing its rarity and expanding the global understanding of this condition. The pathogenesis of PIG appears to be complex and could involve yet unidentified genetic or non-genetic mechanisms. Immunosuppressive therapy, especially with corticosteroids and CNIs, has shown promise in managing PIG, but there is a need for more research to establish standardized treatment protocols.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.