Lisinopril and kidney protection
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Lisinopril and Kidney Protection: A Comprehensive Review
Introduction to Lisinopril and Kidney Protection
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is widely used for managing hypertension and heart failure. Its potential benefits extend to kidney protection, particularly in patients with diabetic nephropathy and other chronic kidney diseases. This article synthesizes findings from multiple studies to elucidate the renoprotective effects of lisinopril.
Lisinopril in Diabetic Nephropathy
Comparative Studies with Other Antihypertensives
Several studies have compared the efficacy of lisinopril with other antihypertensive agents in patients with diabetic nephropathy. A study comparing lisinopril with nisoldipine in hypertensive type 1 diabetic patients found that while both drugs had similar effects on blood pressure, lisinopril significantly reduced albuminuria, a marker of kidney damage, by 52% from baseline, whereas nisoldipine did not show such an effect 1. Another study comparing lisinopril with atenolol in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients demonstrated that lisinopril reduced albuminuria by 45%, compared to only 12% with atenolol, despite similar blood pressure reductions in both groups 23.
Long-Term Effects
Long-term studies have shown that lisinopril can slow the progression of kidney disease. In a 42-month study, lisinopril was found to reduce the rate of decline in glomerular filtration rate (GFR) more effectively than atenolol, particularly in the initial phase of treatment 3. This suggests that lisinopril not only controls blood pressure but also offers additional kidney protection.
Lisinopril in Non-Diabetic Nephropathies
Mild Proteinuric Non-Diabetic Nephropathies
Lisinopril has also been studied in patients with non-diabetic chronic kidney diseases. In patients with mild proteinuria, lisinopril was more effective than other antihypertensive agents in slowing the progression of renal insufficiency. Over a follow-up period of approximately 22.5 months, patients treated with lisinopril showed a significantly slower decline in renal function compared to those on alternative therapies 7.
Adriamycin Nephropathy
In models of adriamycin-induced nephropathy, lisinopril has been shown to reduce proteinuria and glomerulosclerosis, indicating its potential to protect against structural kidney damage. The antiproteinuric effect of lisinopril was found to predict long-term protection against renal damage, supporting the hypothesis that reducing proteinuria is a key mechanism of its renoprotective action 9.
Mechanisms of Renoprotection
Oxidative Stress and Inflammation
Lisinopril's renoprotective effects are partly attributed to its ability to reduce oxidative stress and inflammation. In hypertensive rat models, lisinopril treatment significantly decreased markers of oxidative stress and improved renal antioxidant enzyme activities, thereby mitigating renal damage 5. Additionally, lisinopril has been shown to regulate renalase, a kidney enzyme involved in blood pressure regulation, further contributing to its protective effects 6.
Combination Therapies
Combining lisinopril with other agents, such as l-arginine, has been explored to enhance its renoprotective effects. In a study on passive Heymann nephritis, a severe model of membranous nephropathy, the combination of lisinopril and l-arginine was more effective in reducing proteinuria and renal damage than either treatment alone 8. However, combination therapy with angiotensin receptor blockers (ARBs) has shown increased risks of adverse events, such as hyperkalemia and acute kidney injury, highlighting the need for careful consideration of combination treatments 10.
Conclusion
Lisinopril has demonstrated significant renoprotective effects in both diabetic and non-diabetic nephropathies. Its ability to reduce albuminuria, slow the decline in GFR, and mitigate oxidative stress and inflammation underscores its potential as a key therapeutic agent in managing chronic kidney diseases. While combination therapies may offer additional benefits, they also pose risks that must be carefully managed. Overall, lisinopril remains a valuable tool in the nephrologist's arsenal for protecting kidney function.
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Most relevant research papers on this topic
Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy.
Both lisinopril and nisoldipine have similar long-term renoprotective effects in hypertensive type 1 diabetic patients with diabetic nephropathy.
RCT
Highly CitedImpact of Lisinopril and Atenolol on Kidney Function in Hypertensive NIDDM Subjects With Diabetic Nephropathy
Lisinopril effectively reduces albuminuria more than atenolol in hypertensive NIDDM patients with diabetic nephropathy, potentially improving kidney function.
RCTHighly CitedLong-Term Effect of Lisinopril and Atenolol on Kidney Function in Hypertensive NIDDM Subjects With Diabetic Nephropathy
Both lisinopril and atenolol effectively reduce kidney function decline in hypertensive NIDDM patients with diabetic nephropathy.
RCTHighly CitedThe effect of swimming exercise on adenine-induced kidney disease in rats, and the influence of curcumin or lisinopril thereon
Moderate swimming exercise, curcumin, or lisinopril alone can significantly improve kidney disease symptoms, but combining them with exercise may provide additional nephroprotection.
RCT
Animal Study
Rigorous JournalLisinopril attenuates renal oxidative injury in l-NAME-induced hypertensive rats
Lisinopril treatment can reduce biochemical alterations in l-NAME-induced hypertensive renal damage caused by oxidative stress.
RCTAnimal StudyLisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy
Lisinopril may reduce adriamycin-induced kidney injury by controlling blood pressure, partially due to increased renalase expression and secretion.
RCTAnimal StudyEffect of Lisinopril on the progression of renal insufficiency in mild proteinuric non-diabetic nephropathies.
Lisinopril has a specific renoprotective effect in addition to blood pressure control in patients with mild proteinuria, slowing the progression of non-diabetic chronic renal diseases.
RCTCombining lisinopril and l-arginine slows disease progression and reduces endothelin-1 in passive Heymann nephritis.
Combining l-arginine with ACE inhibitors can slow disease progression and reduce endothelin-1 in patients with severe nephropathy not fully responsive to ACE inhibition.
Antiproteinuric effect predicts renal protection by angiotensin-converting enzyme inhibition in rats with established adriamycin nephrosis.
Angiotensin-converting enzyme inhibition lowers proteinuria and prevents glomerulosclerosis in rats with established adriamycin nephrosis, with individual short-term antiproteinuric effects predicting protection against glomerular damage.
Non-RCTAnimal StudyHighly CitedCombined angiotensin inhibition for the treatment of diabetic nephropathy.
Combination therapy with an ACE inhibitor and an ARB is associated with an increased risk of adverse events in patients with diabetic nephropathy.
RCT
Large Human TrialHighly Cited