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ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling.

Westerweel PE, Joles JA, den Ouden K, Goldschmeding R, Rookmaaker MB, Verhaar MC - Nephron Extra (2012)

Bottom Line: AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance.Proteinuria, however, is effectively prevented by ACE-I treatment.Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT

Background/aims: ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment.

Methods: Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12), dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were left untreated (n = 14). All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28.

Results: Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels.

Conclusions: In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.

No MeSH data available.


Related in: MedlinePlus

Development of proteinuria over the course of anti-Thy1 glomerulonephritis. Induction of anti-Thy1 glomerulonephritis caused a transient rise in proteinuria in untreated rats (CON aThy1), which was not affected by treatment with calcium-antagonist amlodipine (Ca-A aThy1), but nearly fully prevented by treatment with the ACE inhibitor perindopril (ACE-I aThy1). * p < 0.05 compared to untreated controls.
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Figure 1: Development of proteinuria over the course of anti-Thy1 glomerulonephritis. Induction of anti-Thy1 glomerulonephritis caused a transient rise in proteinuria in untreated rats (CON aThy1), which was not affected by treatment with calcium-antagonist amlodipine (Ca-A aThy1), but nearly fully prevented by treatment with the ACE inhibitor perindopril (ACE-I aThy1). * p < 0.05 compared to untreated controls.

Mentions: In control rats, induction of glomerulonephritis caused an increase in urinary protein excretion peaking at day 7 (fig. 1). ACE-I treatment significantly reduced the development of proteinuria and resulted in normalization of proteinuria at day 14 when proteinuria was still high in controls (p < 0.01 for treatment interaction in two-way ANOVA for time and treatment interaction). Ca-A treatment did not affect the development of proteinuria (fig. 1).


ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling.

Westerweel PE, Joles JA, den Ouden K, Goldschmeding R, Rookmaaker MB, Verhaar MC - Nephron Extra (2012)

Development of proteinuria over the course of anti-Thy1 glomerulonephritis. Induction of anti-Thy1 glomerulonephritis caused a transient rise in proteinuria in untreated rats (CON aThy1), which was not affected by treatment with calcium-antagonist amlodipine (Ca-A aThy1), but nearly fully prevented by treatment with the ACE inhibitor perindopril (ACE-I aThy1). * p < 0.05 compared to untreated controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3318936&req=5

Figure 1: Development of proteinuria over the course of anti-Thy1 glomerulonephritis. Induction of anti-Thy1 glomerulonephritis caused a transient rise in proteinuria in untreated rats (CON aThy1), which was not affected by treatment with calcium-antagonist amlodipine (Ca-A aThy1), but nearly fully prevented by treatment with the ACE inhibitor perindopril (ACE-I aThy1). * p < 0.05 compared to untreated controls.
Mentions: In control rats, induction of glomerulonephritis caused an increase in urinary protein excretion peaking at day 7 (fig. 1). ACE-I treatment significantly reduced the development of proteinuria and resulted in normalization of proteinuria at day 14 when proteinuria was still high in controls (p < 0.01 for treatment interaction in two-way ANOVA for time and treatment interaction). Ca-A treatment did not affect the development of proteinuria (fig. 1).

Bottom Line: AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance.Proteinuria, however, is effectively prevented by ACE-I treatment.Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT

Background/aims: ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment.

Methods: Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12), dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were left untreated (n = 14). All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28.

Results: Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels.

Conclusions: In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.

No MeSH data available.


Related in: MedlinePlus