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Tubular Mechanisms in Proteinuria

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Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance

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Abstract

Chronic progressive nephropathies, independent of the type of initial insult, are often associated with high levels of urinary protein excretion. In addition to well established glomerular role in proteinuria, recent studies have shown that proximal tubular cell plays important role in development of proteinuria both under physiologic and pathologic conditions. Many single-site mutations and complete PTC dysfunction result in a high level of albuminuria, without any histologic or electron microscopy structural alterations in the glomerular filtration barrier. Reabsorption of filtered albumin involves a low-capacity/high-affinity megalin-cubulin receptor-mediated process and a high-capacity/low-affinity, process that could be fluid-phase endocytosis. Future studies are warranted examining proteinuria not only as a glomerular impairment but also as proximal tubule dysfunction and may lead to many new advances in the diagnosis and treatment of proteinuric states.

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Abbreviations

AKI:

Acute kidney injury

AP1:

Activator protein 1

BAD:

Bcl-2 associated death promoter

BASP:

Brain abundant signal protein 1

Bcl-2:

B cell lymphoma 2

Bcl-xL:

B-cell lymphoma-extra large

BMP:

Bone morphogenic protein

DAMP:

Danger-associated molecular patterns

DT:

Diphtheria toxin

EGF:

Epidermal growth factor

EMT:

Epithelial-to-mesenchymal transition

ER:

Endoplasmic reticulum

ERK:

Extracellular signal related kinases

FADD:

Fas associated protein with death domain

FcRn:

Neonatal Fc receptor

FITC:

Fluorescein isothiocyanate

HMG-CoA:

3-hydroxy-3-methylglutaryl CoA

IgG:

Immunoglobulin

IL:

Inter-leukin

K d :

Dissociation constant

kD:

Kilo dalton

MAP:

Mitogen activated protein

MCP:

Monocyte chemoattractant protein

MHC:

Major histocompatibility complex

MWF:

Munich-Wistar Fromter

NF-kB:

Nuclear factor kappa-light chain-enhancer of activated B cells

NHE3:

Na+/H+ exchanger isoform3

NLR:

Nod like Receptor

NLRP3:

NOD- like receptor family Pyrin domain containing 3

OK:

Opossum kidney

PDGF:

Platelet derived growth factor

PKB:

Protein kinase B

PPAR:

Peroxisome proliferator activated receptor

PT:

Proximal tubule

PTC:

Proximal tubular cell

RANTES:

Regulated on activation normal T cell expressed and secreted

RAP:

Receptor associated protein

RCT:

Random control trial

TGF:

Tumor growth factor

TIMP:

Tissue inhibitors of metalloproteinases

TLR:

Toll-like receptors

UTP:

Uridine Tri-phosphate

α SMA:

α-Smooth muscle actin

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Authors and Affiliations

  1. The Roudebush VA Medical Centre, Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Sudhanshu K. Verma & Bruce A. Molitoris

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  1. Sudhanshu K. Verma
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  2. Bruce A. Molitoris
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Correspondence to Bruce A. Molitoris .

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  1. Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA

    Judith Blaine

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Verma, S.K., Molitoris, B.A. (2016). Tubular Mechanisms in Proteinuria. In: Blaine, J. (eds) Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance. Springer, Cham. https://doi.org/10.1007/978-3-319-43359-2_3

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