#3741 A CASE OF PODOCYTIC INFOLDING GLOMERULOPATHY WITH DIABETES MELLITUS, NEPHROTIC RANGE PROTEINURIA AND POSITIVE ANTI-PLA2R IN SERUM
Authors: Andronikidi Paraskevi Eva , Palamaris Kostas , Athanasiadou Virginia , Plavoukou Styliani , Panokostas Dimitrios , Gakiopoulou Harikleia , Grapsa Eirini 
Published: June 2023

Abstract

Background and Aims
Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality which was first proposed as a new disease entity in 2008. It is characterized by glomerular basement membrane (GBM) bubbling viewable by light microscopy, due to extensive trapping of podocytic cytoplasm fragments and cell membrane projections within the GBM. Electron microscopy reveals podocyte infolding and invagination into the glomerular basement membranes (GBMs). Most of the cases reported worldwide, indicate that PIG usually co-exists with autoimmune diseases. In this case we present a diabetic patient with no other autoimmune disease in his medical history, whose biopsy was characterized as PIG.

Method
A 60-year-old Caucasian man with a 5-year history of type II diabetes mellitus, hyperlipidemia, hypertension, hyperuricemia and benign colon polyps, was noted by his family physician to have proteinuria. He had been treated with an angiotensin II receptor blocker, statin, and allopurinol for 5 years and he was well regulated. At the point of admission, his 24-h urine collection showed 4,5gr of urine protein. His creatinine at the time was normal (0,89mg/dl), no hypoalbuminemia, no edema or deregulation of hyperlipidemia was noted. His fundoscopy at this point had no diabetic lesions. In the immunological work up, we found normal values of autoantibodies ANA, anti-dsDNA, anti-ENA, complement screening C3, C4, serum and urine protein electrophoresis - immunofixation. Everything was within normal limits except from serum autoantibodies to Phospholipase A2 Receptor of podocytes which was tested with ELISA and valued 35 RU/mL (&lt;20RU/mL).
In the following 9 months his proteinuria remained at the same levels. Due to the persistent nephrotic range proteinuria (&gt;3.5gr/24h) a kidney biopsy was performed. Biopsy was evaluated under light microscope (histochemistry for Congo-Red and immunohistochemistry for C4d, PLA2R and DNAJB9 included), immunofluorescence and electron microscope.

Results
The renal biopsy included 8 glomeruli, 3 of them globally sclerosed (37.5%), the rest enlarged with mild to moderate mesangial matrix increase and thickening of the GBMs, without spikes, pin holes or reduplications. Immunohistochemistry for C4d, PLA2R and DNAJB9 was negative. Immunofluorescence revealed nothing noticeable (no staining of IgG, IgA, IgM, C3, C1q, C4, κ-λ chains) apart from a moderate linear albumin staining. Without electron microscopy the whole picture was rather reminiscent of mild to moderate lesions of diabetic nephropathy.
On electron microscopy, no classical electron-dense deposits were found. Effacement of podocytes’ foot processes was multi-segmental. More importantly, podocytic cytoplasmic processes invaginating into the GBMs were observed, accompanied by scattered endomembranous, partially microspherular microstructures, sometimes with adjacent unclear small pyknotic areas. The biopsy report concluded that although light microscopy and immunofluorescence findings could indicate diabetic nephropathy, the electron microscopy lesions suggest the diagnosis of PIG.

Conclusion
To our knowledge, this is the first reported case with PIG and anti-PLA2R antibodies detected in the serum, without clear histological evidence of membranous nephropathy. Our patient was diabetic for five years with no diabetic lesions in fundoscopy. Although PIG has been reported mainly in the context of autoimmune diseases, the coexistence with diabetes or its possible role in PIG's pathogenesis has not been addressed. The treatment of this peculiar morphologically disease, still remains an open query for physicians.