**1. Introduction**

Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are diseases with primary damage to podocytes (primary podocytopathies), clinically manifested by high proteinuria and nephrotic syndrome [1,2]. FSGS is characterized

**Citation:** Chebotareva, N.V.; Vinogradov, A.; Brzhozovskiy, A.G.; Kashirina, D.N.; Indeykina, M.I.; Bugrova, A.E.; Lebedeva, M.; Moiseev, S.; Nikolaev, E.N.; Kononikhin, A.S. Potential Urine Proteomic Biomarkers for Focal Segmental Glomerulosclerosis and Minimal Change Disease. *Int. J. Mol. Sci.* **2022**, *23*, 12607. https://doi.org/ 10.3390/ijms232012607

Academic Editors: Márcia Carvalho, Luís Belo and Eleni Bairaktari

Received: 7 July 2022 Accepted: 6 October 2022 Published: 20 October 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

by the presence of sclerosis in parts (segmental) of at least one glomerulus (focal) in a kidney biopsy specimen, when examined by light microscopy, immunofluorescence, or electron microscopy. Minimal change disease (MCD) is the leading cause of the nephrotic syndrome in children (approximately 90 percent) and in a minority of adults (approximately 10 percent) [3]. Light microscopy in case of MCD shows only a minor abnormality in the glomeruli, immunohistological methods display no deposits of immunoglobulins and complements, and electron microscopy reveals a diffuse loss of podocyte foot processes. Development of the nephrotic syndrome is due to the damage of the podocyte, foot process effacement and detachment of the podocyte from the glomerular basement membrane (GBM). As a result, proteins pass through the defects of the GBM and proteinuria develops. The onset of both diseases—FSGS and MCD, is usually acute with a severe nephrotic syndrome. A decrease in kidney function at the onset of the disease is diagnosed in 25–50% of patients, hematuria in 50%, and arterial hypertension in 20% of patients with FSGS [2,4].

Patients with MCD, as well as some patients with FSGS, respond well to steroid therapy [5]. However, 25–50% have steroid resistance—a severe form of FSGS. Severe FSGS is characterized by high proteinuria, renal impairment in the initial stages, and an unfavorable prognosis on the progression of renal dysfunction [2,4,6–8].

In primary FSGS, a putative circulating factor that is toxic to the podocyte causes generalized podocyte dysfunction. Secondary FSGS generally occurs as an adaptive phenomenon due to the reduction of the nephron mass or direct toxicity from drugs or viral infections. The circulating factor in FSGS and MCD is still unknown, and therefore the study of specific mechanisms that are involved in podocyte damage is ongoing. This knowledge could improve our understanding of the pathogenetic mechanisms of these diseases. Approaches based on mass spectrometry (MS) are the most objective and sensitive tools that have already provided most of the currently known information on the content of peptides and proteins in urine in various nephropathies [9–12]. The urinary proteome contains mainly (up to 70%) proteins and peptides of renal origin [13,14]. In general, this approach is the most appropriate for the search for potential biomarkers and mechanisms related to the development and progression of kidney diseases.

The aim of our study was to characterize changes in the urinary proteomic profiles of patients with different course of focal segmental glomerulosclerosis and minimal change disease to determine their specific biomarkers.
