Mechanism Underlying Selective Albuminuria in Minimal Change Nephrotic Syndrome

As water and solutes are filtered through the slit membrane, it is an a priori concept that a slit membrane is an essential filtration barrier for proteins, including albumin. However, in cases of minimal change nephrotic syndrome, the number of slit membranes is reduced by the foot process effacement and tight junction-like cell adhesion. Furthermore, albumin endocytosis is enhanced in the podocytes under condition of minimal change disease, and albumin is selectively transported by the albumin receptor FcRn. Suppressing the endocytosis of albumin with anti-FcRn antibody decreases the urinary protein level. The expression of motor molecules, such as cytoplasmic dynein 1 and myosin IX, is increased in the podocytes under conditions of minimal change nephrotic syndrome, suggesting the enhanced transport of vesicles containing albumin. Podocyte vesicle transport may play an important role in the pathology of selective albuminuria in cases of nephrotic syndrome.

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Decreased Podocyte Vesicle Transcytosis and Albuminuria in APC C-Terminal Deficiency Mice with Puromycin-Induced Nephrotic Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms222413412 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13412

Author(s):

Saaya Hatakeyama ◽

Akihiro Tojo ◽

Hiroshi Satonaka ◽

Nami O. Yamada ◽

Takao Senda ◽

...

Keyword(s):

Electron Microscopy ◽

Nephrotic Syndrome ◽

Basal Area ◽

Minimal Change Nephrotic Syndrome ◽

Cytoplasmic Dynein ◽

Renal Tissue ◽

Minimal Change ◽

Vesicle Transport ◽

Kidney Size ◽

Foot Process

In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced.

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Foot process fusion and glomerular filtration rate in minimal change nephrotic syndrome

Kidney International ◽

10.1038/ki.1984.76 ◽

1984 ◽

Vol 25 (4) ◽

pp. 696-700 ◽

Cited By ~ 44

Author(s):

Sven-Olof Bohman ◽

Georg Jaremko ◽

Ann-Britt Bohlin ◽

Ulla Berg

Keyword(s):

Nephrotic Syndrome ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Foot Process

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Mechanisms of Glomerular Albumin Filtration and Tubular Reabsorption

International Journal of Nephrology ◽

10.1155/2012/481520 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 89

Author(s):

Akihiro Tojo ◽

Satoshi Kinugasa

Keyword(s):

Early Stage ◽

Collecting Duct ◽

Distal Tubule ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Membrane Rupture ◽

Filtration Barrier ◽

Podocyte Detachment ◽

Foot Process

Albumin is filtered through the glomerulus with a sieving coefficient of 0.00062, which results in approximately 3.3 g of albumin filtered daily in human kidneys. The proximal convoluted tubule reabsorbs 71%, the loop of Henle and distal tubule 23%, and collecting duct 3% of the glomerular filtered albumin, thus indicating that the kidney plays an important role in protein metabolism. Dysfunction of albumin reabsorption in the proximal tubules, due to reduced megalin expression, may explain the microalbuminuria in early-stage diabetes. Meanwhile, massive nonselective proteinuria is ascribed to various disorders of the glomerular filtration barrier, including podocyte detachment, glomerular basement membrane rupture, and slit diaphragm dysfunction in focal segmental glomerulosclerosis, membranous nephropathy, and other glomerulonephritis. Selective albuminuria associated with foot process effacement and tight junction-like slit alteration is observed in the patients with minimal-change nephrotic syndrome, and the albumin uptake is enhanced in the podocyte cell body, possibly mediated by albumin receptors in the low-dose puromycin model. The role of enhanced podocyte albumin transport needs to be investigated to elucidate the mechanism of the selective albuminuria in minimal-change disease.

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