Losartan and kidney damage
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Losartan and Kidney Damage: A Comprehensive Review
Introduction to Losartan and Kidney Health
Losartan, an angiotensin II receptor antagonist, is widely used to manage hypertension and protect kidney function, particularly in patients with diabetes and chronic kidney disease (CKD). This article synthesizes recent research on the effects of losartan on kidney damage, highlighting its benefits and potential risks.
Losartan's Protective Effects in Diabetic Nephropathy
Renal Benefits in Type 2 Diabetes
Losartan has been shown to confer significant renal benefits in patients with type 2 diabetes and nephropathy. A large-scale study involving 1513 patients demonstrated that losartan significantly reduced the incidence of a doubling of serum creatinine concentration and end-stage renal disease (ESRD) by 25% and 28%, respectively, compared to placebo1. Additionally, losartan reduced proteinuria by 35%, indicating its effectiveness in slowing the progression of renal disease beyond its blood pressure-lowering effects1.
Combination Therapy in Diabetic Nephropathy
While combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) like losartan can decrease proteinuria, it also poses safety concerns. A study on combination therapy with losartan and lisinopril in patients with type 2 diabetes found no significant benefit in reducing the progression of kidney disease and highlighted increased risks of hyperkalemia and acute kidney injury7. This suggests that while losartan alone is beneficial, combining it with other similar agents requires careful consideration.
Losartan in Acute Kidney Injury and Chronic Kidney Disease
Acute Kidney Injury (AKI) to Chronic Kidney Disease (CKD) Transition
Losartan has shown promise in reducing the progression from AKI to CKD. In a murine model, losartan administration post-AKI significantly reduced mortality, blood pressure, albuminuria, azotemia, and kidney fibrosis compared to controls, indicating its potential to mitigate long-term kidney damage following AKI9.
Comparative Efficacy in CKD
In a comparative study between losartan and amlodipine in patients with proteinuric CKD and hypertension, losartan was more effective in reducing urinary protein excretion over a 12-month period, suggesting its superior renoprotective effects5. This reduction in proteinuria is crucial as it is a marker of kidney damage and a predictor of disease progression.
Mechanisms of Renoprotection
Renin-Angiotensin System (RAS) and Renal Dopaminergic System (RDS) Balance
Losartan helps maintain a balance between the RAS and RDS, which is crucial for renal sodium management and inflammation control. In a study on fructose-overloaded rats, losartan prevented metabolic and hemodynamic alterations, reduced pro-inflammatory and pro-fibrotic markers, and prevented renal damage, highlighting its role in maintaining renal homeostasis3.
Biomarkers of Kidney Injury
Losartan's effectiveness in reducing kidney injury is also reflected in biomarkers. In a study on nondiabetic proteinuric kidney disease, losartan significantly decreased urinary kidney injury molecule 1 (KIM-1) levels, a sensitive biomarker for early tubular damage, paralleling the reduction in proteinuria4. This suggests that losartan not only reduces clinical markers of kidney damage but also biochemical indicators of tubular injury.
Potential Risks and Considerations
Risk of Renal Impairment
Despite its benefits, losartan can pose risks, particularly in patients with preexisting renal impairment or those on concomitant diuretics. A case report highlighted renal impairment in a patient with a history of type II diabetes and vascular disease after starting losartan, emphasizing the need for careful monitoring in at-risk populations10.
Prophylactic Use in Nephrotoxicity
Losartan, when used prophylactically, has shown some protective effects against nephrotoxicity induced by agents like cisplatin. However, its combination with other protective agents like vitamin E did not enhance its protective effects, suggesting potential pharmacokinetic or pharmacodynamic interactions that need further investigation6.
Conclusion
Losartan offers significant renoprotective benefits, particularly in patients with diabetic nephropathy and CKD, by reducing proteinuria and slowing disease progression. However, its use requires careful consideration of potential risks, especially in patients with preexisting renal conditions. Ongoing research and long-term studies are essential to fully understand the balance between its benefits and risks in various patient populations.
Sources and full results
Most relevant research papers on this topic
Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
Losartan significantly reduces the risk of kidney damage and end-stage renal disease in patients with type 2 diabetes and nephropathy, while maintaining overall cardiovascular health.
RCT
Large Human Trial
Highly CitedThe effect of angiotensin 1-7 and losartan on renal ischemic/reperfusion injury in male rats
Losartan significantly reduces kidney damage after ischemia/reperfusion in male rats, suggesting its potential as a protective agent against kidney damage.
RCT
Animal StudyLosartan prevents the imbalance between renal dopaminergic and renin angiotensin systems induced by fructose overload. l-Dopa/dopamine index as new potential biomarker of renal dysfunction.
Losartan effectively prevents the imbalance between the renin angiotensin and renal dopaminergic systems induced by fructose overload, preventing hypertension and kidney damage.
RCTAnimal StudyEffect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial.
Losartan, sodium restriction, and hydrochlorothiazide treatment decrease urinary KIM-1 levels in nondiabetic chronic kidney disease patients with proteinuria, indicating reduced tubular damage.
RCTHighly CitedRenoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension--a report of the Japanese Losartan Therapy Intended for the Global Renal Protection in Hypertensive Patients (JLIGHT) study.
Losartan reduces proteinuria in patients with chronic kidney disease and hypertension, potentially contributing to its renal protective benefit beyond blood pressure control.
RCTHighly CitedAdministration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats.
Vitamin E and losartan as prophylaxes showed some protective effects, but the combination of both did not protect against cisplatin-induced nephrotoxicity in rats.
RCTAnimal StudyCombined 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.
RCTLarge Human TrialHighly CitedLosartan
Losartan effectively reduces the risk of developing kidney disease and death in type 2 diabetes patients, with similar effects to enalapril on kidney function.
RCTLarge Human TrialLosartan reduces ensuing chronic kidney disease and mortality after acute kidney injury
Losartan can reduce chronic kidney disease and mortality after acute kidney injury, with hydralazine showing no similar beneficial effect.
Non-RCTAnimal StudyRenal Impairment Associated with Losartan
Losartan may cause renal impairment in patients at risk for renal failure, so clinicians should be aware of this potential risk when prescribing the drug.
Case Report