Role of Podocyte in Kidney Disease

BANTAO Journal, 2015

Glomerular disease is the most common cause of endstage renal disease (ESRD), accounting for almost two thirds of cases. In glomerular disease, alterations of po-docytes are of particular importance. Podocyte loss represents a central mediator of glomerular sclerosis. Toxic, genetic, immune, infectious, oxidant, metabolic, hemody-namic, and other mechanisms can all target the podo-cytes. These mechanisms provide new insight into the unique dynamic microenvironment that each individual podocyte inhabits and how it can turn hostile to survival. At the same time, they raise new therapeutic challenges to preserve glomerular function by containing podocyte injury and limiting its spread, both in podo-cytopathies and in other progressive glomerular diseases. Treatment strategies should aim at enhancing podocyte survival. The renin-angiotensin axis blockade, apart from its antifibrotic and intraglomerular hemodynamic effects, has an important role in preventing podocyte loss. However, only...

Journal of Clinical Investigation, 2001

The renal glomerulus, the site of plasma ultrafiltration and the production of primary urine (1), is the locus of a number of progressive disorders that lead to chronic renal insufficiency. Before the advent of renal replacement therapies, these diseases invariably led to death by uremia. Still, while these treatments save, or at least extend, patient's lives, they do so at an enormous price, both in human and financial terms. The podocyte and focal glomerulosclerosis The prevention of chronic renal insufficiency would require therapies that specifically interfere with the pathogenesis of the various underlying glomerular diseases. Disappointingly however, the molecular mechanisms involved lie in uncharted territory. These conditions can result from varied causes: systemic metabolic disorders, such as diabetes; autoimmune complex formation, as occurs in membranous and lupus nephropathy; or primary podocyte diseases, such as steroid-sensitive minimal change nephrosis, or the steroid-insensitive condition focal segmental glomerulosclerosis (FSGS). Other than diabetes, FSGS now represents the leading cause of renal insufficiency, both in the general patient population and among those whose disease recurs following transplantation. The basis for the increased prevalence of FSGS in recent years is as mysterious as its pathogenesis, and even the best therapies for this disorder are strictly empirical. However, the recent emergence of the visceral glomerular epithelial cell, or podocyte, as the culprit in this and several other […]

American Journal of Biomedical Science & Research, 2021

Compared to primary glomerulopathies, secondary glomerulopathies refer to those in which glomerular damage is part of a complex clinical picture, caused by different processes: immunological, tumors, hereditary, infections or drugs, the classic examples are triggered by the systemic lupus erythematosus (SLE), diabetes, among others See Tables 1&2 [4]. During years, glomerulopathies have been closely related to chronic kidney disease (CKD) [5], occupying the first places of CKD triggers according to the 2017 report of the "The United States Renal Data Am J Biomed Sci & Res

American Journal of Nephrology, 2018

Background: Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury demonstrated by renal biopsy that can arise from a diverse range of causes and mechanisms. It has an estimated incidence of 7 per 1 million and is the most common primary glomerular disorder leading to end-stage renal disease in the United States. This review focuses on damage to the podocyte and the consequences of this injury in patients with FSGS, the genetics of FSGS, and approaches to treatment with a focus on the effects on podocytes. Summary: The podocyte is central to the glomerular filtration barrier and is particularly vulnerable because of its highly differentiated post-mitotic phenotype. The progressive structural changes involved in the pathology of FSGS include podocyte foot process effacement, death of podocytes and exposure of the glomerular basement membrane, filtration of nonspecific plasma proteins, expansion of capillaries, misdirected filtration at points of synechiae, and me...

Journal of the American Society of Nephrology, 2017

Podocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3-6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.

Frontiers in Endocrinology, 2015

Journal of the American Society of Nephrology, 2005

Glomerular injury and proteinuria in diabetes (types 1 and 2) and IgA nephropathy is related to the degree of podocyte depletion in humans. For determining the causal relationship between podocyte depletion and glomerulosclerosis, a transgenic rat strain in which the human diphtheria toxin receptor is specifically expressed in podocytes was developed. The rodent homologue does not act as a diphtheria toxin (DT) receptor, thereby making rodents resistant to DT. Injection of DT into transgenic rats but not wild-type rats resulted in dose-dependent podocyte depletion from glomeruli. Three stages of glomerular injury caused by podocyte depletion were identified: Stage 1, 0 to 20% depletion showed mesangial expansion, transient proteinuria and normal renal function; stage 2, 21 to 40% depletion showed mesangial expansion, capsular adhesions (synechiae), focal segmental glomerulosclerosis, mild persistent proteinuria, and normal renal function; and stage 3, >40% podocyte depletion showed segmental to global glomerulosclerosis with sustained high-grade proteinuria and reduced renal function. These pathophysiologic consequences of podocyte depletion parallel similar degrees of podocyte depletion, glomerulosclerosis, and proteinuria seen in diabetic glomerulosclerosis. This model system provides strong support for the concept that podocyte depletion could be a major mechanism driving glomerulosclerosis and progressive loss of renal function in human glomerular diseases.

Frontiers in Bioscience, 2011

Kidney International, 1998

Podocytes undergo phenotypic changes and express macrophagicassociated markers in idiopathic collapsing glomerulopathy. Collapsing glomerulopathy (CG), a severe form of focal segmental glomerulosclerosis (FSG), is characterized by tuft retraction and consolidation in numerous glomeruli and changes in podocyte morphology and topography. Other glomeruli are less affected. Collapsing glomerulopathy is also characterized by tubulointerstitial atrophy and fibrosis. The pathophysiology of the glomerular and tubulointerstitial lesions is poorly understood. We studied renal tissue of five Black and three White patients, all human immunodeficiency virus (HIV) negative, with nephrotic syndrome, renal failure, and histological evidence of CG. Immunohistochemistry identified normal podocyte phenotypes by podocalyxin, vimentin and complement receptor 1 (CR1) labeling. Three monoclonal antibodies were used to further characterize podocyte epitopes: anti-CD68 clone KP1, anti-CD68 clone PG-M1 and anti-M130 clone M18 (Ber-MAC3). Light microscopy of collapsed glomeruli showed podocyte swelling, vacuolization, multinucleation, "cobblestone-like" alignment around the glomerular tuft, and pseudo-crescent formation in Bowman's space. In collapsed glomeruli, podocalyxin, vimentin and CR1 labeling tagged both normal and vacuolated podocytes still attached to the GBM, but labeling was not found in cobblestone-like podocytes or in podocytes detached from the GBM. Conversely, numerous podocytes undergoing detachment and shedding into Bowman's space expressed macrophagic-associated epitopes. Cells with macrophagic-associated epitopes clumped in cystically dilated tubules and were aligned in tubules of smaller caliber. Their appearance was that of viable cells. There was no morphologic indication that these cells expressing macrophage-associated antigens originated from outside the glomeruli or outside the tubules. We conclude that in CG podocytes detach from the GBM, lose their normal podocytic phenotype and acquire macrophage differentiation antigens. The presence of cells with such antigens in tubular lumens suggests that detached metaplastic podocytes progress along the tubule or, alternatively, that CG tubular cells also undergo metaplastic changes into macrophage-like cells.

Nature Reviews Disease Primers, 2020

The majority of diseases underlying chronic kidney disease (CKD) present with proteinuria, that is, loss of plasma proteins into the urine. Proteinuric kidney diseases can be divided into glomerular or non-glomerular forms, depending on whether protein loss occurs across the glomerular filtration barrier or results from insufficient reabsorption of filtered protein by the proximal tubule 1 . Glomerular proteinuria is defined by a predominance of albumin whereas, in non-glomerular forms, albumin is only a minor component. Proteinuria and proteinuria-related symptoms are the only or the main clinical presentation of diseases affecting podocytes, which are 'octopus-like' highly specialized cells in the glomerulus that act as part of the filter 2-4 . Causes of podocyte injury include all forms of immune complex glomerulonephritis that engender distinct histopathological patterns; for example, subepithelial localization of immune complexes in membranous nephropathy causes direct podocyte injury and massive proteinuria. By contrast, podocyte injuries without immune complex deposits produce different histopathological lesion patterns evident on biopsy, of which four types can be distinguished: diffuse mesangial sclerosis (DMS), which