Podocyte infolding glomerulopathy: Clinical insights from two case studies in Malaysia

Podocyte infolding glomerulopathy (PIG) is a rare glomerular disorder characterised by the infolding of podocytes into the glomerular basement membrane (GBM) with the presence of intramembranous cytoplasmic microspherules or microtubules. Most patients with PIG presented with nephrotic or subnephrotic proteinuria accompanied with microscopic haematuria. The condition is often associated with autoimmune diseases.

Recently, two cases of PIG were reported in Malaysia for the first time involving two female patients aged 25 and 36 years. The first patient had a history of systemic lupus erythematosus (SLE), peripheral neuropathy, anti-nuclear matrix protein 2 (NXP2)-positive antibody, autoimmune hypothyroidism, and primary ovarian failure. She presented with persistent nephrotic range proteinuria and haematuria. Meanwhile, the second patient with history of SLE presented at rheumatology clinic with bilateral pedal oedema, frothy urine, and haematuria. The electron microscopy (EM) analysis of the first patient revealed widespread and extensive invagination of podocyte cytoplasmic processes into the GBM, forming subepithelial clusters of microspherules and microtubules and separated by an intervening basement membrane. Likewise, extensive infolding of podocyte cytoplasmic processes into the GBM were found in the second case, and the intervening basement membrane separated the microspherules and microtubules.

These findings confirmed the diagnosis of PIG, and the patients were treated with Prednisolone, maintaining normal creatinine level during follow-up. In summary, PIG is a rare and new glomerular disease which has been known to be associated with connective tissue diseases, predominantly affecting young individuals with a favourable clinical outcome.