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Unilateral ureteral obstruction: beyond obstruction

  • Nephrology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Unilateral ureteral obstruction is a popular experimental model of renal injury. However, the study of the kidney response to urinary tract obstruction is only one of several advantages of this model. Unilateral ureteral obstruction causes subacute renal injury characterized by tubular cell injury, interstitial inflammation and fibrosis. For this reason, it serves as a model both of irreversible acute kidney injury and of events taking place during human chronic kidney disease. Being a unilateral disease, it is not useful to study changes in global kidney function, but has the advantage of a low mortality and the availability of an internal control (the non-obstructed kidney). Experimental unilateral ureteral obstruction has illustrated the molecular mechanisms of apoptosis, inflammation and fibrosis, all three key processes in kidney injury of any cause, thus providing information beyond obstruction. Recently this model has supported key concepts on the role in kidney fibrosis of epithelial–mesenchymal transition, tubular epithelial cell G2/M arrest, the anti-aging hormone Klotho and renal innervation. We now review the experimental model and its contribution to identifying novel therapeutic targets in kidney injury and fibrosis, independently of the noxa.

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Abbreviations

α-SMA:

Alpha-smooth muscle actin

ACE:

Angiotensin-converting enzyme

AKI:

Acute kidney injury

Alk3:

Activin-like kinase-3

AngII:

Angiotensin II

ARB:

Angiotensin receptor blocker

B1R:

Kinin B1 receptor

BMP-7:

Bone morphogenetic protein-7

CGRP:

Calcitonin gene-related peptide

CKD:

Chronic kidney disease

ECM:

Extracellular matrix

EGFR:

Epithelial growth factor

EMT:

Epithelial to mesenchymal transition

HE4:

Human epididymis protein 4

H/E:

Hematoxilyn/eosin staining

HIPK2:

Homeo-domain-interacting protein kinase 2

ICAM-1:

Intercelullar adhesion molecule-1

MAPK:

Mitogen-acivated protein kinase

MCP-1:

Macrophages chemoattractant protein-1

NMDA:

N-methyl-d-aspartate

NMDAR:

N-methyl-d-aspartate receptor

OPN:

Osteopontin

PAI-1:

Plasminogen activator inhibitor-1

PPARα:

Peroxisome proliferator-activated receptor alpha

RIPK1:

Receptor-interacting serine/threonine protein kinase 1

RIPK2:

Receptor-interacting serine/threonine protein kinase 2

TGF-β1:

Transforming growth factor-beta 1

TNFR1:

Tumor necrosis factor receptor-1

TNFR2:

Tumor necrosis factor receptor-2

TNFα:

Tumor necrosis factor-alpha

TMS:

Trichrome Masson’s staining

TWEAK:

TNF-like weak inducer of apoptosis

UUO:

Unilateral ureteral obstruction

VCAM-1:

Vascular cell adhesion molecule-1

VDR:

Vitamin D receptor

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Acknowledgments

The study was supported by the following: grant support: FIS 081564, PS09/00447, PI07/0020, CP08/1083, ISCIII-RETIC, REDinREN/RD06/0003, REDin-REN/RD06/0004, FEDER funds, RD12/0021, Comunidad de Madrid/CIFRA S2010/BMD-2378; salary support: FIS to ABM, MDSN, ABS, MCI; FIS and IIS-FJD to AMR; Fundación Conchita Rábago to ACU and SB; Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO.

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Authors and Affiliations

  1. Unidad de Diálisis, IIS-Fundación Jiménez Díaz, Av. Reyes Católicos, 2, 28040, Madrid, Spain

    Alvaro C. Ucero, Alberto Benito-Martin, Maria C. Izquierdo, Ana B. Sanz, Adrian M. Ramos, Sergio Berzal, Marta Ruiz-Ortega, Jesus Egido & Alberto Ortiz

  2. Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 2-4, 28029, Madrid, Spain

    Marta Ruiz-Ortega, Jesus Egido & Alberto Ortiz

  3. IDIPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain

    Maria D. Sanchez-Niño

  4. Fundación Renal Iñigo Álvarez de Toledo-IRSIN, C/José Abascal, 42, 28003, Madrid, Spain

    Alberto Ortiz

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  1. Alvaro C. Ucero
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  2. Alberto Benito-Martin
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  3. Maria C. Izquierdo
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  5. Ana B. Sanz
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  9. Jesus Egido
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  10. Alberto Ortiz
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Correspondence to Alberto Ortiz.

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Ucero, A.C., Benito-Martin, A., Izquierdo, M.C. et al. Unilateral ureteral obstruction: beyond obstruction. Int Urol Nephrol 46, 765–776 (2014). https://doi.org/10.1007/s11255-013-0520-1

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  • DOI: https://doi.org/10.1007/s11255-013-0520-1

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