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February 24, 2005Journal of the American Society of Nephrology

Regression of Glomerulosclerosis with High-Dose Angiotensin Inhibition Is Linked to Decreased Plasminogen Activator Inhibitor-1

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Why the study?

Does high-dose AT1RA or ACEI regress glomerulosclerosis in a rat model of 5/6 nephrectomy?

Population

Adult male Sprague Dawley rats with 5/6 nephrectomy (Nx) and established glomerulosclerosis

Comparison

High-dose angiotensin II type 1 receptor… vs Control with no further treatment (CONT)

Design

Preclinical, Rats were divided into groups with equal biopsy sclerosis

Follow-up

4 weeks

Authors

LMLijun MaHenry Ford Health SystemSNShinya NakamuraAkita UniversityJAJean‐Claude AldigierCentre National de la Recherche Scientifique

Discussion

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Implication

Hypothesis-generating for AT1RA-mediated glomerulosclerosis regression in experimental models; human translation untested.

Structured PICO

Does high-dose AT1RA or ACEI regress glomerulosclerosis in a rat model of 5/6 nephrectomy?

P
Population
Adult male Sprague Dawley rats with 5/6 nephrectomy (Nx) and established glomerulosclerosis
I
Intervention
High-dose angiotensin II type 1 receptor antagonist (AT1RA), high-dose angiotensin I converting enzyme inhibitor (ACEI), or varying AT1RA+ACEI combinations for 4 weeks
C
Comparator
Control with no further treatment (CONT)
O
Outcome
Change in glomerulosclerosis from biopsy (8 weeks post-Nx) to autopsy (12 weeks post-Nx)surrogate

High-dose angiotensin inhibition can mediate the regression of existing glomerulosclerosis in a rat model, linked to decreased plasminogen activator inhibitor-1.

Limitations

  • Potential confounding effect as some groups had higher BP and proteinuria

Cite This Study

Ma et al. (2005) studied this question.

synapsesocial.com/papers/6a7043bfce524a4339c40592https://doi.org/10.1681/asn.2004060492
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function.1993 · 406 citations
  2. 2Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis.1995 · 535 citations
  3. 3Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes2001 · 6,044 citations