Aqueous garlic extract improves renal clearance via vasodilatory/antioxidant mechanisms and mitigated proteinuria via stabilization of glomerular filtration barrier

In recent years, several publications reported that nanoparticles larger than the kidney filtration threshold were found intact in the urine after being injected into laboratory mice. This theoretically should not be possible, as it is widely known that the kidneys prevent molecules larger than 6–8 nm from escaping into the urine. This is interesting because it implies that some nanoparticles can overcome the size limit for renal clearance. What kinds of nanoparticles can “bypass” the glomerular filtration barrier and cross into the urine? What physical and chemical characteristics are essential for nanoparticles to have this ability? And what are the biomolecular and cellular mechanisms that are involved? This review attempts to answer those questions and summarize known reports of renal-clearable large nanoparticles.

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Faculty Opinions recommendation of Janus kinase 2/signal transducer and activator of transcription 3 inhibitors attenuate the effect of cardiotrophin-like cytokine factor 1 and human focal segmental glomerulosclerosis serum on glomerular filtration barrier.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725428053.793530397 ◽

2017 ◽

Author(s):

Jochen Reiser

Keyword(s):

Glomerular Filtration ◽

Focal Segmental Glomerulosclerosis ◽

Janus Kinase ◽

Signal Transducer ◽

Janus Kinase 2 ◽

Glomerular Filtration Barrier ◽

Filtration Barrier ◽

Segmental Glomerulosclerosis ◽

Transcription 3

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Faculty Opinions recommendation of Intracellular calcium signaling regulates glomerular filtration barrier permeability: the role of the PKGIα-dependent pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726705461.793522765 ◽

2016 ◽

Author(s):

Bellamkonda Kishore ◽

Daria Ilatovskaya

Keyword(s):

Calcium Signaling ◽

Intracellular Calcium ◽

Glomerular Filtration ◽

Glomerular Filtration Barrier ◽

Barrier Permeability ◽

Filtration Barrier ◽

Intracellular Calcium Signaling ◽

Dependent Pathway

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Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

Cells ◽

10.3390/cells10071815 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1815

Author(s):

Jan Boeckhaus ◽

Oliver Gross

Keyword(s):

Glomerular Filtration ◽

Alport Syndrome ◽

Large Scale ◽

Case Series ◽

Hereditary Diseases ◽

Glomerular Filtration Barrier ◽

Early Effect ◽

Filtration Barrier ◽

First Case ◽

Sodium Glucose Cotransporter

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

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Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

Scientific Reports ◽

10.1038/s41598-021-85040-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cleo C. L. van Aanhold ◽

Manon Bos ◽

Katrina M. Mirabito Colafella ◽

Marie-Louise P. van der Hoorn ◽

Ron Wolterbeek ◽

...

Keyword(s):

Glomerular Filtration ◽

Early Stage ◽

Vascular Inflammation ◽

Angiogenesis Inhibitor ◽

Serum Levels ◽

Dependent Manner ◽

Glomerular Filtration Barrier ◽

Soluble Thrombomodulin ◽

Filtration Barrier ◽

Glomerular Endothelium

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

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Nck Proteins Maintain the Adult Glomerular Filtration Barrier

Journal of the American Society of Nephrology ◽

10.1681/asn.2009010056 ◽

2009 ◽

Vol 20 (7) ◽

pp. 1533-1543 ◽

Cited By ~ 64

Author(s):

Nina Jones ◽

Laura A. New ◽

Megan A. Fortino ◽

Vera Eremina ◽

Julie Ruston ◽

...

Keyword(s):

Glomerular Filtration ◽

Glomerular Filtration Barrier ◽

Filtration Barrier

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Abstract 516: Knockdown of the Hypertension Associated Gene NOSTRIN Alters Glomerular Barrier Function in Zebrafish (Danio rerio)

Hypertension ◽

10.1161/hyp.60.suppl_1.a516 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Torsten Kirsch ◽

Jessica Kaufeld ◽

Ron Korstanje ◽

Dirk Hentschel ◽

Hermann Haller ◽

...

Keyword(s):

Glomerular Filtration ◽

Barrier Function ◽

Morphological Changes ◽

Glomerular Filtration Barrier ◽

Cell Dysfunction ◽

Larval Zebrafish ◽

Filtration Barrier ◽

Important Regulator ◽

Glomerular Barrier ◽

Prime Source

The bioavailability of nitric oxide (NO) has been associated with the development and progression of vascular and renal disease. NOSTRIN (for eNOS Traffic Inducer) has primarily been recognized as one important regulator of eNOS, the prime source of NO in the cardiovascular system, with a possible role in the pathogenesis of pre-eclampsia and the development of increased intrahepatic resistance in liver disease. Here, we identified NOSTRIN in the center of a QTL-overlap region in rat and human trait loci that are associated with hypertension. Glomerular NOSTRIN expression is detectable in podocytes in human and rat glomeruli and podocytic NOSTRIN expression is diminished in hypertensive kidney disease. We show that knockdown of NOSTRIN alters the glomerular filtration barrier function in larval zebrafish, inducing proteinuria and leading to ultrastructural morphological changes on the endothelial as well as epithelial side and the GBM of the glomerular capillary loop. We also demonstrate that NOSTRIN interacts with proteins associated with the podocyte slit membrane. We conclude that NOSTRIN expression is an important factor for the integrity of the glomerular filtration barrier. Disease related alteration of NOSTRIN expression may not only affect the vascular endothelium and therefore contribute to endothelial cell dysfunction but may also contribute to the development of podocyte disease and proteinuria.

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