Lisinopril aki
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Lisinopril and Acute Kidney Injury (AKI): Insights from Recent Research
Introduction to Lisinopril and AKI
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is commonly used to manage hypertension and heart failure. However, its role in acute kidney injury (AKI) has been a subject of extensive research. This article synthesizes findings from multiple studies to provide a comprehensive understanding of the relationship between lisinopril and AKI.
Lisinopril's Protective Effects Against Drug-Induced AKI
Doxorubicin-Induced AKI
A study investigated the protective effects of lisinopril against doxorubicin (DOX)-induced AKI in male Wistar rats. DOX, a widely used anticancer agent, is known for its nephrotoxic effects. The study found that oral administration of lisinopril (20 mg/kg) for 15 consecutive days significantly mitigated DOX-induced kidney damage. Key markers such as serum creatinine, blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1) were reduced, while total antioxidant capacity (TAC) in kidney tissues increased. Additionally, there was a notable decrease in cleaved caspase-3 and NF-κB immunostainings, indicating reduced apoptosis and inflammation in kidney tissues1.
Risks of Dual Renin-Angiotensin System Blockade
Increased Incidence of AKI
The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) Study highlighted the risks associated with dual renin-angiotensin system (RAS) blockade using lisinopril and losartan. The study found that the incidence of AKI was significantly higher in patients receiving combination therapy compared to those on monotherapy (12.2 vs. 6.7 per 100 patient-years). Despite the increased risk of AKI, patients in the combination therapy group showed better recovery of kidney function and lower 30-day mortality rates2.
Clinical Case of Dual Therapy
A clinical case further illustrated the complications of dual RAS blockade. A patient with nephrotic range proteinuria and elevated serum creatinine levels was initially treated with losartan. When lisinopril was added to the regimen, the patient developed AKI, necessitating a reduction in the losartan dose. This case underscores the need for careful monitoring and dose adjustments when using dual RAS blockade to manage proteinuria3.
Nephrotoxin Exposure and AKI
Lisinopril as a Nephrotoxin
A retrospective cohort study at the University of Iowa Hospital identified lisinopril as one of the common nephrotoxins associated with AKI in adults. The study found that high nephrotoxin exposure, including lisinopril, significantly increased the risk of developing AKI, particularly stage 2-3 AKI, and was associated with higher mortality rates4.
Interaction with Other Medications
Another case report highlighted the potential for AKI when lisinopril is used in combination with other medications. A patient with chronic kidney disease (CKD) developed AKI after starting linagliptin, a DPP-IV inhibitor, while on lisinopril. The hypothesized mechanism involved renal hypoperfusion due to linagliptin-induced natriuresis and intravascular volume contraction, exacerbated by lisinopril's effects on renal autoregulation5.
Conclusion
Lisinopril has demonstrated both protective and harmful effects in the context of AKI. While it can mitigate drug-induced nephrotoxicity, its use, especially in combination with other RAS blockers or nephrotoxic drugs, requires careful monitoring. Clinicians should weigh the benefits against the risks and adjust treatment protocols accordingly to prevent AKI and ensure optimal patient outcomes.
Sources and full results
Most relevant research papers on this topic
Anti-oxidant impact of Lisinopril and Enalapril against acute kidney injury induced by doxorubicin in male Wistar rats: involvement of kidney injury molecule-1
Lisinopril and Enalapril can reduce the adverse effects of doxorubicin on acute kidney injury in rats, potentially increasing its clinical use.
RCT
Animal StudyIncidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System Blockade.
Dual renin-angiotensin system blockade is associated with an increased risk of AKI compared to monotherapy, but AKI in monotherapy leads to lower kidney function recovery rates, higher mortality, and higher kidney disease progression.
RCT
Large Human TrialDual therapy difficulties in angiotensin blockade for proteinuria: a teachable moment.
The patient's proteinuria improved with losartan, but creatinine levels remained elevated, and lisinopril use led to fatigue and hypotension, ultimately leading to discontinuing lisinopril use and restoring normal blood pressure.
Case ReportNephrotoxin Exposure and Acute Kidney Injury in Adults
Nephrotoxin exposure in adults is common and significantly associated with acute kidney injury development, including stage 2–3 AKI and mortality.
Observational StudyAcute Kidney Injury Associated with Linagliptin
Linagliptin may cause acute kidney injury in patients with chronic kidney disease, requiring caution and monitoring when combined with ACE-inhibitors.
Case ReportGISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico.
Lisinopril alone or combined with transdermal glyceryl trinitrate significantly reduces overall mortality and severe ventricular dysfunction after acute myocardial infarction.
RCTLarge Human Trial
Highly CitedLisinopril attenuates acute hypoxic pulmonary vasoconstriction in humans.
Lisinopril significantly reduces the pulmonary pressor response to hypoxemia without decreasing baseline mean arterial pressure or total pulmonary vascular resistance, suggesting it may be a useful adjunctive treatment for hypoxemic pulmonary hypertension.
RCTLisinopril ameliorates paraquat-induced lung fibrosis.
Lisinopril effectively protects against paraquat-induced lung fibrosis, potentially due to inhibition of angiotensin II or proline moiety.
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.
RCTOral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice
Oral lisinopril increases ACE2 in tissues relevant to COVID-19 transmission and pathogenesis, but the addition of losartan prevents these increases in ACE2 levels.
RCTAnimal Study