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Angiotensin II receptor blockade and progression of nondiabetic-mediated renal disease
1Rush University Hypertension Center, Rush Presbyterian/St. Luke's Medical Center, Chicago, Illinois, USA.
Abstract:
While the bulk of the existing data are in diabetic renal disease, there are some animal and clinical studies that compare the effects of angiotensin I (AT-1) receptor antagonists to angiotensin converting enzyme (ACE) inhibitors in renal disease of nondiabetic origin. Based on these data, preservation of renal function and morphology occurs with AT-1 receptor antagonists in animal models where renal injury is hemodynamically mediated such as in the remnant kidney. Conversely, in non-hemodynamically mediated renal injury such as in puromycin nephrosis, AT-1 receptor antagonists have not consistently protected against declines in glomerular filtration rate or development of interstitial fibrosis. This may, however, be related to dosage, since high doses of AT-1 receptor antagonists show some protection against progression in these models. It is too early, however, to make judgments regarding the clinical impact of the AT-1 receptor antagonists on progression of nondiabetic renal disease. The result of the ELITE trial support the concept that progression of renal dysfunction associated with heart failure is ameliorated to a similar extent between ACE inhibitors and the AT-1 receptor antagonist, losartan. The AT-1 receptor antagonist group also had fewer side effects including the absence of cough as well as a lower, albeit not statistically significant, incidence of hyperkalemia. Thus, the emerging database supports the concept that AT-1 receptor antagonists have an efficacy similar to ACE inhibitors for preserving renal function and morphology in hemodynamically mediated renal injury. It is unclear, however, whether this drug class will reduce immunologically-mediated renal injury.
Insights
Angiotensin II (AT-1) receptor antagonists preserve kidney function in hemodynamically mediated injury, similar to ACE inhibitors. Their role in non-diabetic renal disease, especially immunologically-mediated injury, requires further investigation.
Area of Science:
- Nephrology
- Pharmacology
- Cardiology
Background:
- Existing data primarily focus on diabetic renal disease.
- Studies compare angiotensin II (AT-1) receptor antagonists and angiotensin converting enzyme (ACE) inhibitors in non-diabetic renal conditions.
- Renal injury can be hemodynamically or non-hemodynamically mediated.
Purpose of the Study:
- To compare the efficacy of AT-1 receptor antagonists and ACE inhibitors in non-diabetic renal disease.
- To evaluate the impact of AT-1 receptor antagonists on renal function and morphology in different types of renal injury models.
- To assess the clinical impact and side effect profile of AT-1 receptor antagonists compared to ACE inhibitors.
Main Methods:
- Review of animal and clinical studies comparing AT-1 receptor antagonists and ACE inhibitors.
- Analysis of data from hemodynamically mediated renal injury models (e.g., remnant kidney).
- Evaluation of data from non-hemodynamically mediated renal injury models (e.g., puromycin nephrosis).
- Consideration of results from the ELITE trial regarding renal dysfunction in heart failure.
Main Results:
- AT-1 receptor antagonists preserve renal function and morphology in hemodynamically mediated injury models.
- Protection against glomerular filtration rate decline and fibrosis is inconsistent in non-hemodynamically mediated injury, potentially dose-dependent.
- The ELITE trial suggests similar amelioration of renal dysfunction in heart failure between ACE inhibitors and losartan (an AT-1 receptor antagonist).
- AT-1 receptor antagonists showed a favorable side effect profile, including less cough and lower hyperkalemia incidence.
Conclusions:
- AT-1 receptor antagonists demonstrate efficacy comparable to ACE inhibitors in preserving renal function and morphology in hemodynamically mediated renal injury.
- The effectiveness of AT-1 receptor antagonists in reducing immunologically-mediated renal injury remains uncertain.
- Further clinical judgment on the impact of AT-1 receptor antagonists in non-diabetic renal disease progression is pending.
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01:29Acute Kidney Injury II: Pathophysiology
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