Is it appropriate to increase lisinopril (Angiotensin-Converting Enzyme Inhibitor) or switch to losartan (Angiotensin II Receptor Blocker) in a 65-year-old male presenting with proteinuria and hypertension?

From the Guidelines

For a 65-year-old male with proteinuria and elevated blood pressure, increasing the lisinopril dose would be the appropriate first-line management rather than switching to losartan. ACE inhibitors like lisinopril are preferred initial agents for patients with proteinuria and hypertension due to their well-established renoprotective effects, as supported by 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 1. The dose should be titrated upward gradually (e.g., from 10mg to 20mg daily) while monitoring blood pressure, renal function, and potassium levels.

Some key points to consider in the management of this patient include:

• The goal blood pressure target for patients with CKD is <130/80 mm Hg, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• ACE inhibitors and ARBs have been shown to reduce proteinuria and slow progression of kidney disease by decreasing intraglomerular pressure through efferent arteriolar dilation, although ACE inhibitors have more robust evidence supporting their use as first-line therapy in this clinical scenario 1.
• Regular monitoring of serum creatinine and potassium is essential, particularly within 1-2 weeks after dose adjustments, as these medications can cause acute kidney injury or hyperkalemia in susceptible individuals.
• If the patient experiences intolerable side effects such as persistent cough, then switching to losartan (an ARB) would be reasonable, with goal doses as outlined in the KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease 1.

It is also important to note that the combination of an ACE inhibitor and an ARB should be avoided due to reported harms demonstrated in several large cardiology trials and in diabetic nephropathy trials 1.

From the FDA Drug Label

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). Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine concentration

Increasing lisinopril or switching to losartan may be considered in a 65-year-old male presenting with proteinuria and hypertension, as losartan has been shown to reduce proteinuria and slow the progression of renal disease in patients with type 2 diabetes and nephropathy 2.

• Key benefits of losartan include a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease, or death, as well as a 25% reduction in sustained doubling of serum creatinine and a 29% reduction in end-stage renal disease.
• Losartan also reduces proteinuria by an average of 34% and slows the decline in glomerular filtration rate by 13%. However, the decision to increase lisinopril or switch to losartan should be made on a case-by-case basis, taking into account the individual patient's specific clinical circumstances and medical history.

From the Research

Treatment Options for Proteinuria and Hypertension

• The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality 3.
• Drugs interfering with the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), should be used as first-line antihypertensive therapy in patients with proteinuria 3, 4.
• ACEIs, such as lisinopril, and ARBs, such as losartan, have a blood pressure-independent antiproteinuric effect and can be used to decrease proteinuria in patients with chronic kidney disease (CKD) 3, 4, 5.

Increasing Lisinopril or Switching to Losartan

• If blood pressure levels are still out of goal, a diuretic should be added to the regimen, or a combination of an ACEI with an ARB or other classes of medications shown to decrease protein excretion should be considered to decrease proteinuria further 3.
• The combination therapy of an ACEI and an ARB can be considered to optimize renoprotection in hypertensive patients with CKD and proteinuria 4, 6.
• Losartan has been shown to decrease proteinuria and urinary angiotensinogen excretion in non-diabetic patients with CKD, and can be considered as an alternative to lisinopril in patients with proteinuria and hypertension 5.

Considerations for Treatment

• The choice of antihypertensive therapy should be based on the individual patient's characteristics, such as the presence of CKD, proteinuria, and hypertension 3, 4.
• The goal of treatment should be to achieve a blood pressure goal of less than 130/80 mmHg in patients with proteinuria to achieve maximal renal and cardiovascular protection 3, 4.
• The treatment regimen should be titrated based on the patient's response to therapy, with the goal of achieving optimal blood pressure control and reducing proteinuria 7.