What is the safest antihypertensive medication for a patient with impaired renal function (GFR in the 50s), mildly elevated liver function tests (LFTs), and sustained mild hypercreatininemia (Creatinine (Cr) 1.16-1.22)?

From the Guidelines

For a patient with a GFR in the 50s, mildly elevated liver function tests, and sustained creatinine of 1.16-1.22, the safest blood pressure medication would be a long-acting calcium channel blocker such as amlodipine, starting at 5 mg daily. This recommendation is based on the fact that calcium channel blockers are generally well-tolerated in patients with reduced kidney function and mild hepatic impairment, as they undergo minimal renal elimination and don't require significant dose adjustments for moderate kidney dysfunction 1. Amlodipine specifically has minimal impact on GFR and doesn't worsen renal function. Some key points to consider when choosing a blood pressure medication for this patient include:

• The patient's GFR is in the 50s, which indicates moderate kidney dysfunction
• The patient has mildly elevated liver function tests, which may affect the metabolism of certain medications
• The patient has a sustained creatinine of 1.16-1.22, which indicates some degree of kidney impairment Considering these factors, the following options may be considered:
• A low-dose thiazide-like diuretic such as chlorthalidone 12.5 mg daily, though careful monitoring of electrolytes and kidney function would be necessary 1
• Beta-blockers, but they require careful dosing with hepatic impairment and are not recommended as first-line agents unless the patient has specific indications like coronary artery disease or heart failure 1
• ACE inhibitors and ARBs, which are beneficial for kidney protection in many cases, but require close monitoring as they can cause acute changes in kidney function, especially in patients with already compromised GFR 1 Regular monitoring of blood pressure, kidney function, and electrolytes is essential regardless of the medication chosen. It's also important to note that the patient's specific clinical context and medical history should be taken into account when making a final decision. In general, the goal is to choose a medication that will effectively control the patient's blood pressure while minimizing the risk of adverse effects and interactions with other medications. The patient's kidney function and liver function should be closely monitored while on the chosen medication.

From the FDA Drug Label

1. 3 Nephropathy in Type 2 Diabetic Patients The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]). Treatment with losartan resulted in a 16% risk reduction in this endpoint (see Figure 4 and Table 4) Treatment with losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality (see Table 4).

The safest blood pressure medication for a patient with GFR in the 50s, LFTs mildly elevated, Cr 1.16-1.22 sustained is losartan.

• Key benefits:
  • Reduced risk of doubling of serum creatinine by 25%
  • Reduced risk of end-stage renal disease (ESRD) by 29%
  • Reduced proteinuria by an average of 34%
  • Reduced rate of decline in glomerular filtration rate during the study by 13% 2 2

From the Research

Patient Profile

• GFR in the 50s
• LFTs mildly elevated
• Cr 1.16-1.22 sustained

Medication Options

• Losartan: an angiotensin II receptor antagonist
• Amlodipine: a calcium channel blocker

Study Findings

• A study published in 2003 3 found that losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.
• Another study published in 2018 4 found that amlodipine is a powerful, well-tolerated, and safe antihypertensive agent that is widely used either alone or as a key component of combination therapy for hypertension.
• A study published in 2003 5 compared the effectiveness, safety, and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension, and found that both drugs were comparably safe and effective treatment options.
• A study published in 2019 6 discussed the importance of measuring glomerular filtration rate (GFR) in patients with CKD, and found that measured GFR can be useful to individualize therapy among patients with CKD.
• A study published in 2019 7 assessed the pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings, and found that the co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction.

Safety Considerations

• Losartan may be a safer option for patients with CKD and hypertension, as it has been shown to have renoprotective effects 3.
• Amlodipine may also be a safe option, as it is a well-tolerated and safe antihypertensive agent 4, 5.
• The combination of amlodipine and losartan may cause additive haemodynamic changes, but it is generally well-tolerated 7.