Irina Bobkova

Heat shock proteins and kidney disease: perspectives of HSP therapy

Heat shock proteins (HSPs) mediate a diverse range of cellular functions, prominently including folding and regulatory processes of cellular repair. A major property of these remarkable proteins, dependent on intracellular or extracellular location, is their capacity for immunoregulation that optimizes immune activity while avoiding hyperactivated inflammation. In this review, recent investigations are described, which examine roles of HSPs in protection of kidney tissue from various traumatic influences and demonstrate their potential for clinical management of nephritic disease. The HSP70 class is particularly attractive in this respect due to its multiple protective effects. The review also summarizes current understanding of HSP bioactivity in the pathophysiology of various kidney diseases, including acute kidney injury, diabetic nephropathy, chronic glomerulonephritis, and lupus nephritis—along with other promising strategies for their remediation, such as DNA vaccination.

New Insights into the Molecular Mechanisms of Podocytes Injury in Diabetes

Pandemia of diabetes mellitus (DM) remains one of the biggest worldwide medical problems associated with dangerous complications, particularly diabetic nephropathy (DN), which is the leading cause of the end-stage renal disease. It was confirmed convincingly today that podocytes injury is implicated primarily or secondarily in various proteinuric glomerular diseases, including DN. The characteristic signs of podocytopathy are podocytes hypertrophy, foot process effacement, detachment from the glomerular basal membrane and apoptosis. Structural and functional alterations of podocytes evolve early, outpacing clinically significant albuminuria. The increasing loss of podocytes is associated with morphological and clinical signs of DN progression. This review details the molecular and cellular events, mediators and signaling pathways that contribute to podocytes injury in DM, discusses the most important achievements, clinical and experimental data in these issues, describes the urinary biomarkers of podocytes injury.

New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus associated with the progressive deterioration of renal function. Although microalbuminuria is considered as a gold standard for DN diagnosis, it has limited predictive powers and specificity as a diagnostic tool for the early stage of DN. Therefore, new biomarkers are required for the early detection of DN. Studies using in vitro and in vivo models of DN have revealed an important role of microRNAs (miRNAs), short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression, in DN development. Recent studies have shown that the dysregulation of miRNAs, which is associated with the key features of DN, such as the mesangial expansion and accumulation of extracellular matrix proteins, is related to fibrosis and glomerular dysfunction. Thus, the up- and downregulation of miRNA expression in the renal tissue or biological fluids, including urine, may represent new biomarkers for the diagnosis and monitoring of DN progression. In this review, we highlight the significance of miRNAs as biomarkers for the early detection of DN and emphasise their potential role as a therapeutic target.

Therapeutic Complement Targeting in ANCA-Associated Vasculitides and Thrombotic Microangiopathy

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of medium-to-small vessels, a relative paucity of immune deposits, and an association with detectable circulating ANCAs. AAVs include granulomatosis with polyangiitis (renamed from Wegeners granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Until recently, AAVs have not been viewed as complement-mediated disorders. However, recent findings predominantly from animal studies demonstrated a crucial role of the complement system in the pathogenesis of AAVs. Complement activation or defects in its regulation have been described in an increasing number of acquired or genetically driven forms of thrombotic microangiopathy. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises as to which AAV patients might benefit from a complement-targeted therapy. Therapies directed against the complement system point to the necessity of a genetic workup of genes of complement components and regulators in patients with AAV. Genetic testing together with pluripotent stem cells and bioinformatics tools may broaden our approach to the treatment of patients with aggressive forms of AAV.

Peculiarities of renal affection in patients with type 2 diabetes mellitus

Диабетическая нефропатия относится к поздним осложнениям сахарного диабета (СД), которое развивается, как правило, у больных с его длительным декомпенси- рованным течением. Диабетическая нефропатия характери- зуется особой формой поражения клубочков ? диабетическим гломерулосклерозом. Наиболее часто встречается его узловая (или нодулярная) форма, которая до недавнего времени считалась патогномоничной для СД.