Should a patient with impaired renal function, elevated alanine transaminase (ALT) and aspartate transaminase (AST), and hypertension be started on losartan (losartan) for its renal protective benefits?

From the Guidelines

Starting losartan is an appropriate choice for this patient with hypertension and reduced kidney function, given its renal protective benefits and effectiveness in blood pressure control, as supported by the 2021 KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease 1. The patient's current blood pressure of 150/90 mmHg and reduced kidney function, with a GFR of 54 and elevated creatinine levels of 1.11-1.28, indicate the need for initiation of antihypertensive therapy. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, losartan is a suitable option for patients with hypertension, with a recommended dose of 50-100 mg daily 1. Losartan, an angiotensin II receptor blocker (ARB), offers dual benefits of blood pressure control and renoprotection by reducing intraglomerular pressure and proteinuria through efferent arteriole dilation. The mild liver enzyme elevations (ALT 44, AST 47) are not contraindications to losartan therapy. It is essential to monitor kidney function and potassium levels within 1-2 weeks after initiation, as ARBs like losartan can cause temporary GFR decreases and hyperkalemia. Lifestyle modifications, including sodium restriction, regular exercise, and weight management, should complement pharmacological treatment. The KDIGO guideline recommends a target systolic blood pressure of <120 mmHg for patients with chronic kidney disease, which can be achieved with losartan therapy, and the guideline also suggests that renin-angiotensin system inhibitors (RASi), such as losartan, can reduce the risk of kidney failure and major cardiovascular events in patients with CKD 1. Therefore, initiating losartan 50 mg once daily, with potential titration to 100 mg daily if blood pressure remains elevated, is a reasonable approach for this patient.

From the FDA Drug Label

8.7 Renal Impairment Patients with renal insufficiency have elevated plasma concentrations of losartan and its active metabolite compared to subjects with normal renal function. No dose adjustment is necessary in patients with renal impairment unless a patient with renal impairment is also volume depleted

5.3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan. Monitor renal function periodically in these patients Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan

The patient has a GFR of 54, which indicates renal impairment.

• Losartan can be used in patients with renal impairment, but no dose adjustment is necessary unless the patient is also volume depleted.
• The patient is not currently on BP meds and has a BP of 150/90, so starting losartan may be beneficial for BP control.
• However, it is essential to monitor renal function periodically due to the patient's renal impairment.
• Losartan may provide renal protective benefits, but this should be weighed against the potential risks, and renal function should be closely monitored 2, 2.

From the Research

Patient Profile

• Average creatinine (Cr) level: 1.11-1.28
• Current glomerular filtration rate (GFR): 54
• Alanine transaminase (ALT) level: 44
• Aspartate transaminase (AST) level: 47
• Blood pressure (BP): 150/90
• Not currently on BP medication

Considerations for Starting Losartan

• Losartan has shown promise in reducing blood pressure and providing renal protection, although its efficacy in this regard is still being studied 3
• The drug has been found to be effective in lowering blood pressure in elderly patients with hypertension, with a similar incidence of treatment-related adverse events as other antihypertensive agents 4
• Losartan may contribute to the regression of left ventricular hypertrophy associated with chronic hypertension and increase exercise capacity in patients with heart failure 4

Renal Protective Benefits

• Angiotensin-converting enzyme (ACE) inhibitors are currently considered the drugs of choice for patients with renal insufficiency due to their ability to reduce intraglomerular hypertension, angiotensin II-induced glomerular growth, proteinuria, and hyperlipidemia 3
• Losartan, an angiotensin II receptor antagonist, has shown potential in providing renal protection, although more research is needed to fully understand its effects 3, 4

Potential Risks and Considerations

• Losartan has been associated with an increase in transaminases in less than 2% of cases, and rare cases of drug-induced liver injury have been reported 5
• The optimal dosing of losartan may vary depending on patient characteristics, such as sex, age, and kidney function 6
• Patients with poorer kidney function and severe heart failure symptoms may not benefit from high-dose losartan 6