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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

Glomerulosclerosis during late-phase anti-Thy1 glomerulonephritis. In kidney sections of rats with late-phase anti-Thy1 glomerulonephritis, a proportion of glomeruli showed signs of segmental glomerulosclerosis, which was histologically quantified using the GSI (see Animals and Methods section for specification of the scoring procedure). The GSI was higher in ACE inhibitor perindopril-treated animals (ACE-I aThy1) than in untreated controls (CON aThy1). Treatment with calcium-antagonist amlodipine (Ca-A aThy1) did not affect the development of glomerulosclerosis. * p < 0.05 compared to untreated controls.
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Figure 3: Glomerulosclerosis during late-phase anti-Thy1 glomerulonephritis. In kidney sections of rats with late-phase anti-Thy1 glomerulonephritis, a proportion of glomeruli showed signs of segmental glomerulosclerosis, which was histologically quantified using the GSI (see Animals and Methods section for specification of the scoring procedure). The GSI was higher in ACE inhibitor perindopril-treated animals (ACE-I aThy1) than in untreated controls (CON aThy1). Treatment with calcium-antagonist amlodipine (Ca-A aThy1) did not affect the development of glomerulosclerosis. * p < 0.05 compared to untreated controls.

Mentions: At day 28, nearly all microaneurysms had resolved, but around one third of glomeruli showed segmental glomerular sclerosis (fig. 2). At day 28, ACE-I-treated animals had a slightly higher average glomerulosclerosis score than controls, which was statistically significant (GSI 0.49 ± 0.07 vs. 0.36 ± 0.03, p < 0.05; fig. 3). To further evaluate possible adverse fibrotic remodeling, we assessed intrarenal intima-media thickness as this was pathologically increased with ACE inhibition in experimental kidney transplantation [17]. Indeed also in our model, ACE-I treatment was associated with signs of renal artery vasculopathy, with a significantly increased wall thickness of the cortical arteriesat day 28 (intima-media surface area 4,046 ± 419 vs. 2,689 ± 195 μm2, p < 0.05; fig. 4). GSI in Ca-A-treated animals did not differ from controls (0.39 ± 0.06 vs. 0.36 ± 0.03, p = not significant; fig. 3), and cortical artery wall thickness was unchanged in untreated controls and Ca-A-treated animals at day 28 (fig. 4).


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)

Glomerulosclerosis during late-phase anti-Thy1 glomerulonephritis. In kidney sections of rats with late-phase anti-Thy1 glomerulonephritis, a proportion of glomeruli showed signs of segmental glomerulosclerosis, which was histologically quantified using the GSI (see Animals and Methods section for specification of the scoring procedure). The GSI was higher in ACE inhibitor perindopril-treated animals (ACE-I aThy1) than in untreated controls (CON aThy1). Treatment with calcium-antagonist amlodipine (Ca-A aThy1) did not affect the development of glomerulosclerosis. * 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 3: Glomerulosclerosis during late-phase anti-Thy1 glomerulonephritis. In kidney sections of rats with late-phase anti-Thy1 glomerulonephritis, a proportion of glomeruli showed signs of segmental glomerulosclerosis, which was histologically quantified using the GSI (see Animals and Methods section for specification of the scoring procedure). The GSI was higher in ACE inhibitor perindopril-treated animals (ACE-I aThy1) than in untreated controls (CON aThy1). Treatment with calcium-antagonist amlodipine (Ca-A aThy1) did not affect the development of glomerulosclerosis. * p < 0.05 compared to untreated controls.
Mentions: At day 28, nearly all microaneurysms had resolved, but around one third of glomeruli showed segmental glomerular sclerosis (fig. 2). At day 28, ACE-I-treated animals had a slightly higher average glomerulosclerosis score than controls, which was statistically significant (GSI 0.49 ± 0.07 vs. 0.36 ± 0.03, p < 0.05; fig. 3). To further evaluate possible adverse fibrotic remodeling, we assessed intrarenal intima-media thickness as this was pathologically increased with ACE inhibition in experimental kidney transplantation [17]. Indeed also in our model, ACE-I treatment was associated with signs of renal artery vasculopathy, with a significantly increased wall thickness of the cortical arteriesat day 28 (intima-media surface area 4,046 ± 419 vs. 2,689 ± 195 μm2, p < 0.05; fig. 4). GSI in Ca-A-treated animals did not differ from controls (0.39 ± 0.06 vs. 0.36 ± 0.03, p = not significant; fig. 3), and cortical artery wall thickness was unchanged in untreated controls and Ca-A-treated animals at day 28 (fig. 4).

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