How does losartan protect kidneys
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Losartan's Protective Effects on Kidney Health
Introduction to Losartan and Kidney Protection
Losartan, an angiotensin II receptor blocker (ARB), is widely recognized for its protective effects on the kidneys, particularly in patients with chronic kidney disease (CKD), hypertension, and diabetes. This article synthesizes findings from multiple studies to elucidate how losartan confers renal protection.
Reduction of Proteinuria in Chronic Kidney Disease
One of the primary mechanisms by which losartan protects the kidneys is through the reduction of proteinuria. In a study comparing losartan with amlodipine in patients with proteinuric CKD and hypertension, losartan significantly reduced 24-hour urinary protein excretion over a 12-month period, whereas amlodipine did not show such an effect . This reduction in proteinuria is crucial as it helps in slowing the progression of kidney damage.
Protection Against Ischemia/Reperfusion Injury
Losartan also demonstrates protective effects against ischemia/reperfusion (I/R) injury, a major cause of acute kidney injury. Research involving male Wistar rats showed that losartan, either alone or in combination with angiotensin 1-7, significantly decreased levels of serum urea nitrogen, creatinine, and other markers of kidney damage following I/R injury . This suggests that losartan can mitigate the adverse effects of I/R by modulating the renin-angiotensin system.
Benefits in Diabetic Nephropathy
In patients with type 2 diabetes and nephropathy, losartan has been shown to reduce the incidence of doubling serum creatinine levels and the progression to end-stage renal disease (ESRD). A large-scale study involving 1513 patients found that losartan reduced the risk of these outcomes by 25% and 28%, respectively, compared to placebo . Additionally, losartan significantly decreased proteinuria by 35%, highlighting its role in managing diabetic nephropathy.
Improvement of Renal Blood Flow and Oxygen Delivery
Losartan also helps in maintaining renal blood flow and oxygen delivery, particularly during hypotensive events induced by anesthesia. In a study with pigs, losartan pre-treatment improved recovery of renal blood flow and oxygen delivery after propofol-induced hypotension, suggesting that losartan can counteract angiotensin II-mediated renal vasoconstriction .
Early Diabetic Nephropathy and Structural Preservation
In a study involving American Indians with type 2 diabetes, losartan was found to preserve kidney structure, particularly in patients with microalbuminuria. The study showed that losartan treatment resulted in lower mesangial fractional volume, indicating less structural damage to the kidneys .
Protection Against Drug-Induced Nephrotoxicity
Losartan has also been studied for its protective effects against nephrotoxicity induced by drugs such as cisplatin. Research indicates that losartan can mitigate oxidative stress and reduce kidney damage markers in cisplatin-treated rats, without affecting the drug's uptake by the kidneys 610. This suggests that losartan can be a valuable adjunct therapy in preventing drug-induced kidney injury.
Modulation of Renal Angiogenesis Factors
Losartan's protective effects extend to conditions like chronic intermittent hypoxia (CIH), often seen in obstructive sleep apnea. Studies have shown that losartan can modulate the renal renin-angiotensin system and angiogenesis factors, thereby reducing peritubular capillary loss and kidney damage in CIH models .
Conclusion
Losartan offers multifaceted protection for the kidneys through mechanisms such as reducing proteinuria, mitigating ischemia/reperfusion injury, preserving kidney structure in diabetic nephropathy, improving renal blood flow, and protecting against drug-induced nephrotoxicity. These benefits make losartan a critical therapeutic agent in managing various forms of kidney disease.
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