The Pathology Lesion Patterns of Podocytopathies: How and why?

Ravaglia, Fiammetta; Melica, Maria Elena; Angelotti, Maria Lucia; Chiara, Letizia De; Romagnani, Paola; Lasagni, Laura

doi:10.3389/fcell.2022.838272

Cited by 4 publications

(4 citation statements)

References 119 publications

(197 reference statements)

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“…Kidney biopsy also allows active and potentially reversible lesions to be distinguished from inactive disease or chronic and irreversible lesions (Table 1 ), and this informs immunotherapy. Active lesions include intravascular neutrophil karyorrhexis or NETosis, immunothrombosis and fibrin deposition, endothelial and mesangial cell proliferation, glomerular leukocytic infiltrates, vascular loop necrosis, cellular crescents (that is, massive hyperplasia of parietal epithelial cells in the Bowman space obstructing glomerular outflow) 10 and periglomerular lymphocyte infiltrates 18 . Glomerular deposits of IgM, IgG, C1q, C3c and C4d or a combination of these support complement activation.…”

Section: Clinical Presentation and Diagnosis Of Gnmentioning

confidence: 99%

Glomerulonephritis: immunopathogenesis and immunotherapy

et al. 2023

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‘Glomerulonephritis’ (GN) is a term used to describe a group of heterogeneous immune-mediated disorders characterized by inflammation of the filtration units of the kidney (the glomeruli). These disorders are currently classified largely on the basis of histopathological lesion patterns, but these patterns do not align well with their diverse pathological mechanisms and hence do not inform optimal therapy. Instead, we propose grouping GN disorders into five categories according to their immunopathogenesis: infection-related GN, autoimmune GN, alloimmune GN, autoinflammatory GN and monoclonal gammopathy-related GN. This categorization can inform the appropriate treatment; for example, infection control for infection-related GN, suppression of adaptive immunity for autoimmune GN and alloimmune GN, inhibition of single cytokines or complement factors for autoinflammatory GN arising from inborn errors in innate immunity, and plasma cell clone-directed or B cell clone-directed therapy for monoclonal gammopathies. Here we present the immunopathogenesis of GN and immunotherapies in use and in development and discuss how an immunopathogenesis-based GN classification can focus research, and improve patient management and teaching.

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Section: Clinical Presentation and Diagnosis Of Gnmentioning

confidence: 99%

Glomerulonephritis: immunopathogenesis and immunotherapy

et al. 2023

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“…Several lines of evidence support the podocyte depletion hypothesis, showing the histological consequences of precise degrees of podocyte loss, from mesangial expansion to focal and ultimately global glomerulosclerosis [ 49 , 50 ]. On the other hand, the amount of podocyte replacement driven by PECs that act as podocyte progenitors, together with the efficient or inadequate differentiation into podocytes, is the other determinant of a successful repair strategy, resulting in maintaining normal glomerular appearance or in the development of glomerular hyperplastic lesions in the Bowman space [ 51 ].…”

Section: The Role Of Kidney Biopsymentioning

confidence: 99%

“…genetic mutations, maladaptive conditions, etc.) [ 4 , 55 , 56 ], and/or an inadequate capacity of PECs to replace lost podocytes usually due to inefficient differentiation [ 51 ], podocyte loss exceeds 20% and segmental denudation of GBM initiates the injury cascade leading to scar formation [ 49 ]. Glomerulosclerosis can be limited in settings of high regenerative potential as in DMS, a pattern of injury found in children younger than 5 years old with NS progressing to end-stage kidney disease (ESKD) [ 57 ].…”

Section: The Role Of Kidney Biopsymentioning

confidence: 99%

Defining diagnostic trajectories in patients with podocytopathies

Cirillo

Lugli

Raglianti

et al. 2022

Clinical Kidney Journal

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Podocytopathies are glomerular disorders in which podocyte injury drives proteinuria and progressive kidney disease. They encompass a broad spectrum of etiologies, resulting in pathological pictures of minimal-changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis or collapsing glomerulopathy. Despite improvement in classifying podocytopathies as a distinct group of disorders, the histological definition fails to catch the relevant biological heterogeneity underlying each case, manifesting as extensive variability in disease progression and response to therapies. Increasing evidence suggests that podocytopathies can result from a single causative factor or a combination of multiple genetic and/or environmental risk factors with different relative contributions, identifying complex physiopathology mechanisms. Consequently, the diagnosis can still be challenging. In recent years, significant advances in genetic, microscopy and biological techniques revolutionized our understanding of the molecular mechanisms underlying podocytopathies, pushing nephrologists to integrate innovative information with more conventional data obtained from kidney biopsy in the diagnostic workflow. In this review, we will summarize current approaches in the diagnosis of podocytopathies, focusing on strategies aimed at elucidating the etiology standing behind the histological picture. We will provide several examples of an integrative view of traditional concepts and new data in patients with suspected podocytopathies, along with a perspective on how a reclassification could help to improve not only diagnostic pathways and therapeutic strategies, but also the management of disease recurrence after kidney transplantation. In the future, the advantages of precision medicine will probably allow diagnostic trajectories to be increasingly sharpened, maximizing therapeutic results and long-term prognosis.

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“…Regardless of the etiology of FSGS, a common feature is that the initial event occurs in podocytes [4]. Podocytes are highly differentiated epithelial cells with limited regenerative capacity.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis

Li¹,

Fan²,

Zhu³

et al. 2023

Kidney Dis

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Background：Podocytes are essential components of the glomerular filtration barrier and essential for the proper filtration function of the glomerulus. Podocyte injury under various stress conditions is the primary pathogenesis and key determinant of focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations of proteinuria or nephrotic syndrome. Summary：Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxidant defenses, mitochondrial dynamics (fusion, fission and mitophagy), and mitochondrial biogenesis, guarantees the sophisticated structure and various functions of podocytes. However, under FSGS pathological conditions, mitochondria encounter oxidative stress, dynamics disturbances, and defective mitochondrial biogenesis. Moreover, mutations in mtDNA and mitochondria-related genes are also strongly associated with FSGS. Based on these evidences, bioactive agents that function to relieve mitochondrial oxidative stress and promote mitochondrial biogenesis have been proven effective in pre-clinical FSGS models. Targeting the mitochondrial network is expected to provide new therapeutic strategies for the treatment of FSGS and delay its progression to end-stage renal disease (ESRD). Key messages：Mitochondrial dysfunction plays a key role in podocyte injury and FSGS progression. This review summarized recent advances in the study of mitochondrial homeostatic imbalance and dysfunction in FSGS and discussed the potential of mitochondria-targeted therapeutics in improving FSGS and retarding its progression to ESRD.

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The Pathology Lesion Patterns of Podocytopathies: How and why?

Cited by 4 publications

References 119 publications

Glomerulonephritis: immunopathogenesis and immunotherapy

Glomerulonephritis: immunopathogenesis and immunotherapy

Defining diagnostic trajectories in patients with podocytopathies

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis

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