Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS

Immunofluorescence (IF) is an important diagnostic tool for renal biopsies, especially evaluating glomerular immune complex deposition. Studies that focus on proximal tubules or tubular basement membrane (TBM) using IF are few. Reportedly, granular immune complex or complement deposits in the TBM are detected in autoimmune diseases [1,2], immunoglobulin abnormalities [3], and viral infections [4]. Linear immunoglobulin G (IgG) deposits in the glomeruli and TBM are observed in diabetic nephropathy [5]. C3 deposition in the TBM was discovered in patients with acute tubular injury (ATI) [6]. There have been no previous reports of IgG deposition in the TBM of patients with focal segmental glomerulosclerosis (FSGS) and ATI. However, we experienced a case of FSGS complicated with ATI. The renal biopsy of this patient showed strong linear IgG deposition in the TBM with detached tubular epithelial cells and granular deposits in the proximal tubular epithelium.

FSGS exhibits a refractory nephrotic syndrome, occasionally leading to end-stage renal disease [7]. FSGS is caused by glomerular podocyte injury, referred to as “podocytopathy,” similar to minimal change nephrotic syndrome (MCNS); however, unlike MCNS, it often exhibits a steroid-resistant course [8]. FSGS is diagnosed based on glomerular findings of renal biopsies, such as focal segmental lesion of sclerosis, adhesion, or visceral epithelial cell hypertrophy, and is classified according to the histological classification (Columbia classification) reported by DʼAgati et al. in 2004 [9]. Pathologists sometimes have difficulty differentiating FSGS and MCNS because FSGS lesions are focal and segmental. A previous report stated that the probability of detecting glomeruli with FSGS lesions on a single-sectioned renal biopsy analysis is significantly lower compared with the serial section; therefore, the sampling problem creates a bias in the pathological diagnosis of FSGS [10].

Nephrotic syndrome, such as FSGS, is triggered by the breakdown of the glomerular filtration barrier (GFB), which is composed of fenestrated endothelium, slit diaphragms of the podocyte foot process, and glomerular basement membrane, forming charge and size barriers. In FSGS, both barriers are impaired, resulting in leakage of large molecular weight proteins, such as IgG, from the glomerular basement membrane (GBM) [11]. We speculate that IgG leaked from the GFB is reabsorbed by the proximal tubular epithelium; thus, it might be detected by IF as granular IgG deposition in the tubular epithelial cell cytoplasm. Furthermore, linear IgG deposition in the TBM can be detectable in renal tissues of patients with FSGS accompanied by ATI with a detachment of the proximal tubular epithelium and exposed TBM to the lumen throughout the final process of reabsorption. Based on these hypotheses, ATI without nephrotic syndrome and ATI with MCNS, which lacks only a charge barrier and does not leak large molecular IgG, might not show IgG deposits in the proximal tubular epithelium or TBM.

Herein, we aimed to clarify whether patients with FSGS complicated with ATI show IgG deposition in the TBM and proximal tubular epithelium, different from ATI with other causes. In addition, we attempted to identify whether it is possible to distinguish FSGS from MCNS by IF study of proximal tubules.

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