Podocytopathies

Nature Reviews Disease Primers, Год журнала: 2020, Номер 6(1)

Опубликована: Авг. 13, 2020

Язык: Английский

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Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment

Biomedicine & Pharmacotherapy, Год журнала: 2018, Номер 101, С. 670 - 681

Опубликована: Март 22, 2018

Язык: Английский

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Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Journal of the American Society of Nephrology, Год журнала: 2018, Номер 29(3), С. 759 - 774

Опубликована: Янв. 10, 2018

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury depletion. Subclasses of include primary, genetic, secondary forms, the latter comprising maladaptive, viral, drug-induced FSGS. Despite sharing certain clinical features, these subclasses differ noticeably in management prognosis. Without an accepted nongenetic biomarker discriminates among types, classification patients is often challenging. This review summarizes including onset severity proteinuria as well presence nephrotic syndrome, may aid identifying specific subtype. The characterized segmental sclerosis must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features pathognomonic for particular subcategory. characteristics foot process effacement on electron microscopy, while helpful discriminating between primary maladaptive FSGS, little utility detecting genetic forms When cannot classified clinicopathologic assessment, analysis should offered. Next generation DNA sequencing enables cost-effective screening multiple genes simultaneously, but determining pathogenicity detected variant A more systematic evaluation patients, suggested herein, will likely improve therapeutic outcomes design future trials

Язык: Английский

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Digital pathology and computational image analysis in nephropathology

Nature Reviews Nephrology, Год журнала: 2020, Номер 16(11), С. 669 - 685

Опубликована: Авг. 26, 2020

Язык: Английский

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Consequences of Glomerular Hyperfiltration: The Role of Physical Forces in the Pathogenesis of Chronic Kidney Disease in Diabetes and Obesity

˜The œNephron journals/Nephron journals, Год журнала: 2019, Номер 143(1), С. 38 - 42

Опубликована: Янв. 1, 2019

<b><i>Background:</i></b> Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for cause-to-effect relationship between hyperfiltration-related physical forces development chronic kidney disease (CKD). <b><i>Summary:</i></b> associated with glomerular tubular hypertrophy. Hyperfiltration mainly due to an increase capillary pressure, which increases tensile stress applied wall structures. In addition, increased ultrafiltrate flow into Bowman’s space heightens shear on podocyte foot processes body surface. These mechanical stresses lead basement membrane (GBM) length ability grow being limited, mismatch develops GBM area covered processes, leading injury, detachment viable podocytes, adherence capillaries parietal epithelium, synechia formation segmental sclerosis. Mechanical also post-filtration structures, resulting dilation urinary spaces, proximal sodium reabsorption hypertrophied epithelial cells activation mediators tubulointerstitial inflammation, hypoxia fibrosis <b><i>Key Messages:</i></b> GH-related leads both adaptive maladaptive changes. flow-related effects play central role pathogenesis disease. Attenuation thus important therapeutic target obesity-induced CKD.

Язык: Английский

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Insights into Glomerular Filtration and Albuminuria

New England Journal of Medicine, Год журнала: 2021, Номер 384(15), С. 1437 - 1446

Опубликована: Апрель 14, 2021

Chronic kidney diseases generally arise from a disordered filtration barrier within glomeruli. This review describes the roles of glomerular capillary pressure, basement membrane, and podocytes in regulating permeability.

Язык: Английский

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Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data

Kidney International, Год журнала: 2019, Номер 95(4), С. 787 - 796

Опубликована: Фев. 27, 2019

Язык: Английский

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mTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans

JCI Insight, Год журнала: 2019, Номер 4(18)

Опубликована: Сен. 18, 2019

The cellular origins of glomerulosclerosis involve activation parietal epithelial cells (PECs) and progressive podocyte depletion. While mammalian target rapamycin-mediated (mTOR-mediated) hypertrophy is recognized as an important signaling pathway in the context glomerular disease, role a compensatory mechanism preventing PEC remains poorly understood. In this study, we show that mTOR activation-related genes were both upregulated intercorrelated biopsies from patients with focal segmental (FSGS) diabetic nephropathy, suggesting pathological roles. Advanced morphometric analyses murine human tissues identified aiming to regulate functional integrity response somatic growth, depletion, even - all absence detectable regeneration. mice, pharmacological inhibition during acute loss impaired remaining podocytes, resulting unexpected albuminuria, activation, glomerulosclerosis. Exacerbated persistent enabled vicious cycle limit its beneficial effects. summary, our data highlight critical protective mTOR-mediated following order preserve integrity,

Язык: Английский

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Organoid single cell profiling identifies a transcriptional signature of glomerular disease

JCI Insight, Год журнала: 2019, Номер 4(1)

Опубликована: Янв. 10, 2019

Podocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte and compensation mechanisms are challenging analyze in vivo. Human organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease regeneration, present an opportunity explore the plasticity podocytes. Here, profiling more than 12,000 single human PSC–derived organoid cultures was used identify robust reproducible cell lineage gene expression shared with developing kidneys based on trajectory analysis. Surprisingly, signature characteristic glomerular epithelial also observed tissue cohort. This correlated proteinuria inverse eGFR, it confirmed independent podocytopathy Three genes particular were further characterized as novel components signature. We conclude that reliably recapitulate developmental program podocytes other lineages profiles seen reactivated disease. Our findings demonstrate approach identifying molecular programs involved pathogenesis glomerulopathies.

Язык: Английский

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Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss

Journal of the American Society of Nephrology, Год журнала: 2020, Номер 31(4), С. 865 - 875

Опубликована: Март 3, 2020

Significance Statement In males with classic Fabry disease, the processes leading to frequent outcome of ESKD are poorly understood. Mutations in gene encoding α -galactosidase A leads globotriaosylceramide accumulation various cell types; podocytes, this progresses age. study 55 disease genotype and/or phenotype, authors found an increasing fraction podocyte cytoplasm occupied by globotriaosylceramide, which plateaued at around age 27 years. At same time, volume continued rise, apparently expense stress (indicated foot process width) and loss. These changes associated urinary protein excretion, a strong prognosticator adverse renal outcomes, reduction GFR, indicating need for early intervention before critical Background Defects lead (GL3) types. glomerular GL3 Of concern, podocytes relatively resistant enzyme replacement therapy replicating, little ability compensate Methods (mean years) we performed unbiased quantitative morphometric electron microscopic studies biopsied kidney samples from patients seven living transplant donors (to serve as controls). We extracted clinical information medical records trial databases. Results Podocyte (proportion GL3) increased up about 27, suggesting that beyond threshold may compromise survival these cells. was injury loss, evidenced width (a generally accepted structural marker injury) decreased number density per volume. Worsening parameters (increasing also excretion—a outcomes disease—as well decreasing GFR. Conclusions Given known association between loss irreversible FSGS global glomerulosclerosis, points important role progression nephropathy indicates therapeutic occurs.

Язык: Английский

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