How does lisinopril protect kidneys
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Lisinopril's Protective Effects on Kidney Function
Introduction to Lisinopril and Kidney Protection
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is widely used to manage hypertension and heart failure. Its role in protecting kidney function, particularly in patients with diabetic nephropathy and other kidney diseases, has been extensively studied. This article synthesizes research findings on how lisinopril protects the kidneys.
Reduction of Albuminuria in Diabetic Nephropathy
One of the primary mechanisms by which lisinopril protects the kidneys is by reducing albuminuria, a condition characterized by excessive albumin in the urine, which is a marker of kidney damage. Studies have shown that lisinopril significantly reduces urinary albumin excretion compared to other antihypertensive treatments. For instance, in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) and diabetic nephropathy, lisinopril reduced albuminuria by 55%, compared to only 15% with atenolol 12. This reduction in albuminuria is crucial as it indicates a slowing down of kidney damage progression.
Preservation of Glomerular Filtration Rate (GFR)
Lisinopril also helps in preserving the glomerular filtration rate (GFR), which is a measure of kidney function. Although the decline in GFR was similar between lisinopril and other treatments like atenolol in some studies, the reduction in albuminuria suggests a protective effect on the kidneys 12. In type 1 diabetic patients with diabetic nephropathy, lisinopril showed a significant reduction in the initial decline of GFR compared to nisoldipine, another antihypertensive drug 4.
Modulation of Renalase and Blood Pressure
Lisinopril's protective effects extend to its influence on renalase, an enzyme involved in the metabolism of catecholamines, which are stress hormones that can affect kidney function. In a study on adriamycin-induced nephropathy in rats, lisinopril treatment resulted in decreased proteinuria, lower systolic blood pressure, and fewer morphological kidney lesions. This was associated with increased renalase expression in the kidney, suggesting that lisinopril may protect the kidneys by modulating renalase levels and reducing blood pressure 3.
Impact on Proliferative and Apoptotic Pathways
In conditions like autosomal recessive polycystic kidney disease (ARPKD), lisinopril has been shown to reduce the activation of proliferative signaling markers and apoptotic pathways. Chronic treatment with lisinopril led to a significant reduction in markers of cell proliferation and apoptosis, which are involved in the progression of kidney cysts and damage. This indicates that lisinopril can beneficially alter cellular pathways to reduce kidney damage 5.
Combination Therapies for Enhanced Protection
Combining lisinopril with other treatments can enhance its protective effects. For example, combining lisinopril with l-arginine, a precursor of nitric oxide, significantly reduced proteinuria and improved kidney function in a rat model of membranous nephropathy. This combination therapy also reduced the levels of endothelin-1, a protein that contributes to kidney damage, more effectively than lisinopril alone 7. Additionally, combining lisinopril with moderate exercise or natural products like curcumin has shown to offer additional nephroprotection in chronic kidney disease models 6.
Conclusion
Lisinopril protects the kidneys through multiple mechanisms, including reducing albuminuria, preserving GFR, modulating renalase levels, and altering proliferative and apoptotic pathways. Its effectiveness can be further enhanced when used in combination with other treatments. These findings underscore the importance of lisinopril in managing kidney diseases, particularly in patients with diabetic nephropathy and other chronic kidney conditions.
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Most relevant research papers on this topic
Long-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.
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 CitedLisinopril 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.
RCT
Animal StudyLong-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.
RCTHighly CitedChronic treatment with lisinopril decreases proliferative and apoptotic pathways in autosomal recessive polycystic kidney disease
Chronic lisinopril treatment can reduce renal cyst development in autosomal recessive polycystic kidney disease by altering proliferative and apoptotic pathways.
Non-RCTAnimal StudyThe 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.
RCTAnimal Study
Rigorous JournalCombining 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.
Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril.
Nifedipine improves kidney transplant function more effectively than lisinopril over a 2-year period in hypertensive renal transplant patients treated with cyclosporin.
RCTHighly 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 CitedEffect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.
ACE inhibitor treatment can slow renal disease progression in type II diabetes mellitus patients, with lisinopril showing the most significant benefit for this group.
RCTLarge Human TrialHighly Cited