Lisinopril acute kidney injury
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Lisinopril and Acute Kidney Injury: A Comprehensive Review
Introduction to Lisinopril and Acute Kidney Injury
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is widely used to manage hypertension, heart failure, and chronic kidney disease. However, its association with acute kidney injury (AKI) has been a subject of extensive research. This article synthesizes findings from multiple studies to provide a clear understanding of the relationship between lisinopril and AKI.
Lisinopril's Protective Effects Against Drug-Induced Nephrotoxicity
Doxorubicin-Induced Acute Kidney Injury
Research has shown that lisinopril can mitigate the nephrotoxic effects of doxorubicin, a common anticancer drug. In a study involving male Wistar rats, lisinopril administration significantly reduced serum creatinine and blood urea nitrogen (BUN) levels, markers of kidney injury. Additionally, it decreased oxidative stress markers such as myeloperoxidase (MPO) and malondialdehyde (MDA), while increasing total antioxidant capacity (TAC) in kidney tissues. These findings suggest that lisinopril can protect against doxorubicin-induced AKI by reducing oxidative stress and inflammation .
Adriamycin Nephropathy
Another study focused on adriamycin-induced nephropathy found that lisinopril not only reduced proteinuria and systolic blood pressure but also increased renalase accumulation in kidney tissues. Renalase is an enzyme that plays a crucial role in kidney function. The study concluded that lisinopril's protective effects might be partially attributed to its ability to regulate renalase expression and secretion, thereby attenuating adriamycin-induced kidney injury .
Adverse Effects and Risks of Lisinopril
Case Reports of AKI
Despite its protective effects in some contexts, lisinopril has been implicated in causing AKI in certain cases. For instance, a 24-year-old man developed AKI while being treated with deferasirox and lisinopril for chronic iron overload. The discontinuation of both drugs led to a significant reduction in serum creatinine levels, indicating that lisinopril contributed to the kidney injury . Another case involved a 26-year-old man who experienced worsening renal azotaemia and AKI while on lisinopril therapy for secondary hypertension. His kidney function did not normalize even after stopping the medication, highlighting the potential severity of lisinopril-induced AKI .
Combination Therapy Risks
Studies have also examined the risks associated with combining lisinopril with other medications. For example, adding lisinopril to losartan, an angiotensin II receptor blocker (ARB), in patients with type 2 diabetes and proteinuria increased the risk of hyperkalemia and AKI. The combination therapy did not show significant benefits in terms of reducing the progression of kidney disease but did increase adverse events, leading to the early termination of the study 47.
Mechanisms of Lisinopril-Induced AKI
Impaired Autoregulation and Hypotension
The mechanisms underlying lisinopril-induced AKI are complex and multifactorial. One hypothesis is that ACE inhibitors like lisinopril impair renal autoregulation, making the kidneys more susceptible to hypotension-induced injury. This is particularly concerning in patients with preexisting chronic kidney disease (CKD) or those on concurrent medications that affect renal perfusion .
Renal Artery Stenosis
In some cases, lisinopril-induced AKI may be linked to underlying conditions such as renal artery stenosis. For instance, a patient with secondary hypertension and renal artery stenosis experienced severe AKI while on lisinopril. The drug's discontinuation did not fully restore kidney function, suggesting that the underlying vascular condition exacerbated the drug's nephrotoxic effects .
Conclusion
Lisinopril has demonstrated both protective and harmful effects on kidney function, depending on the context and patient-specific factors. While it can mitigate drug-induced nephrotoxicity in some cases, it also poses a risk of AKI, particularly when used in combination with other medications or in patients with underlying renal conditions. Clinicians should carefully monitor kidney function and consider individual patient risk factors when prescribing lisinopril to minimize the potential for acute kidney injury.
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