Molecular mechanisms of diabetic kidney disease

Journal of Clinical Investigation, Год журнала: 2014, Номер 124(6), С. 2333 - 2340

Опубликована: Июнь 2, 2014

Diabetic kidney disease (DKD) is the leading cause of failure worldwide and single strongest predictor mortality in patients with diabetes. DKD a prototypical gene environmental interactions. Tight glucose control significantly decreases incidence, indicating that hyperglycemia-induced metabolic alterations, including changes energy utilization mitochondrial dysfunction, play critical roles initiation. Blood pressure control, especially medications inhibit angiotensin system, only effective way to slow progression. While considered microvascular complication diabetes, growing evidence indicates podocyte loss epithelial dysfunction important roles. Inflammation, cell hypertrophy, dedifferentiation by activation classic pathways regeneration further contribute Concerted clinical basic research efforts will be needed understand pathogenesis identify novel drug targets.

Язык: Английский

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Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis

Nature Reviews Nephrology, Год журнала: 2016, Номер 12(8), С. 453 - 471

Опубликована: Июнь 6, 2016

Язык: Английский

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Focal Segmental Glomerulosclerosis

Clinical Journal of the American Society of Nephrology, Год журнала: 2017, Номер 12(3), С. 502 - 517

Опубликована: Фев. 27, 2017

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology primary FSGS plasma factor with responsiveness to immunosuppressive therapy and risk recurrence after transplant-important characteristics. In contrast, adaptive associated excessive nephron workload due increased body size, reduced capacity, or single glomerular hyperfiltration certain diseases. Additional etiologies are now recognized as drivers FSGS: high-penetrance genetic mutations in one nearly 40 genes, virus-associated FSGS, medication-associated FSGS. Emerging data support the identification sixth category: APOL1 allele-associated individuals sub-Saharan ancestry. classification particular patient relies on integration findings from clinical history, laboratory testing, biopsy, some patients, testing. biopsy can be helpful, clues provided by features light microscopy (

Язык: Английский

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Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease

The Lancet Diabetes & Endocrinology, Год журнала: 2014, Номер 2(5), С. 417 - 426

Опубликована: Май 1, 2014

Язык: Английский

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Cellular and molecular mechanisms of kidney fibrosis

Molecular Aspects of Medicine, Год журнала: 2018, Номер 65, С. 16 - 36

Опубликована: Июнь 22, 2018

Язык: Английский

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A Potential Role for Mechanical Forces in the Detachment of Podocytes and the Progression of CKD

Journal of the American Society of Nephrology, Год журнала: 2014, Номер 26(2), С. 258 - 269

Опубликована: Июль 25, 2014

Loss of podocytes underlies progression CKD. Detachment from the glomerular basement membrane (GBM) rather than apoptosis or necrosis seems to be major mechanism podocyte loss. Such detachment viable may caused by increased mechanical distending and shear forces and/or impaired adhesion GBM. This review considers challenges that lead loss GBM under physiologic pathophysiologic conditions, including hypertension, hyperfiltration, hypertrophy, outflow filtrate subpodocyte spaces. Furthermore, we detail cellular mechanisms which respond these challenges, discuss protective effects angiotensin blockade, note questions must addressed better understand relationship between

Язык: Английский

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A Review of Podocyte Biology

American Journal of Nephrology, Год журнала: 2018, Номер 47(Suppl. 1), С. 3 - 13

Опубликована: Янв. 1, 2018

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked dysfunctions renal glomerulus involving function podocyte epithelial cells, including foot process effacement.Developments imaging technology are improving knowledge detailed structure human and cortex. processes attach themselves glomerular capillaries at basement membrane (GBM) forming intercellular junctions form slit diaphragm filtration barriers maintain normal function. Damage this area implicated disease. Injured podocytes undergo effacement whereby they lose their spread out, leading reduction barrier Effacement typically presence proteinuria focal segmental glomerulosclerosis, minimal change disease, diabetes. It thought be due breakdown actin cytoskeleton processes, complex contractile apparatuses allow dynamically reorganize according changes requirements. The depletion correlates development sclerosis chronic kidney Focal adhesion complexes interact underlying GBM bind within prevent detachment. Key Messages: Knowledge helping advance our mechanics filtering process, opening way variety new potential applications for clinical targeting.

Язык: Английский

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Molecular mechanisms of renal aging

Kidney International, Год журнала: 2017, Номер 92(3), С. 569 - 579

Опубликована: Июль 18, 2017

Язык: Английский

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Glomerular Aging and Focal Global Glomerulosclerosis

Journal of the American Society of Nephrology, Год журнала: 2015, Номер 26(12), С. 3162 - 3178

Опубликована: Июнь 3, 2015

Kidney aging is associated with an increasing proportion of globally scarred glomeruli, decreasing renal function, and exponentially ESRD prevalence. In model systems, podocyte depletion causes glomerulosclerosis, suggesting age-associated glomerulosclerosis could be caused by a similar mechanism. We measured number, size, density, glomerular volume in 89 normal kidney samples from living deceased donors poles nephrectomies. Podocyte nuclear density decreased age due to combination number per glomerulus increased volume. Compensatory cell hypertrophy prevented change the tuft occupied podocytes. Young kidneys had high reserve (podocyte >300 106µm3), but 70–80 years age, average to, <100 106µm3, corresponding hypertrophy. older detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at younger ages podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio). Moreover, kidneys, proteinaceous material accumulated Bowman space glomeruli low density. subset these mass events occurred association becoming binucleate (mitotic catastrophe) subsequent wrinkling capillaries, collapse, periglomerular fibrosis. young patients underlying diseases pathologic identified focal global glomerulosclerosis. reduction may therefore directly lead all progressive can considered superimposed accelerators this process.

Язык: Английский

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Obesity and chronic kidney disease

AJP Endocrinology and Metabolism, Год журнала: 2022, Номер 324(1), С. E24 - E41

Опубликована: Ноя. 16, 2022

The prevalence of obesity has increased dramatically during the past decades, which been a major health problem. Since 1975, number people with worldwide nearly tripled. An increasing studies find as driver chronic kidney disease (CKD) progression, and mechanisms are complex include hemodynamic changes, inflammation, oxidative stress, activation renin-angiotensin-aldosterone system (RAAS). Obesity-related is characterized by glomerulomegaly, often accompanied localized segmental glomerulosclerosis lesions. In these patients, early symptoms atypical, microproteinuria being main clinical manifestation nephrotic syndrome rare. Weight loss RAAS blockers have protective effect on obesity-related CKD, but even so, significant proportion patients eventually progress to end-stage renal despite treatment. Thus, it critical comprehend underlying CKD create new tactics for slowing or stopping progression. this review, we summarize current knowledge disease, its pathological future perspectives

Язык: Английский

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