From the Guidelines
For patients with diabetes and chronic kidney disease (CKD), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are the most optimal first-line antihypertensive medications, as they provide renoprotective effects beyond blood pressure control. The most recent and highest quality study, 1, recommends targeting a systolic blood pressure (SBP) of <120 mm Hg, which is consistent with the KDIGO guideline. Specific options include lisinopril (ACEI) starting at 5-10 mg daily, gradually increasing to 20-40 mg daily as tolerated, or losartan (ARB) starting at 25-50 mg daily, increasing to 50-100 mg daily.
These medications are preferred because they not only lower blood pressure but also reduce proteinuria and slow the progression of diabetic kidney disease by decreasing intraglomerular pressure. They provide renoprotective effects beyond blood pressure control by blocking the renin-angiotensin-aldosterone system, which is often overactive in diabetic nephropathy. The ADA/KDIGO consensus report, 1, also recommends using ACEIs or ARBs for patients with type 1 or type 2 diabetes and CKD, titrated to the maximum antihypertensive or highest tolerated dose.
When starting these medications, monitor serum creatinine and potassium levels within 1-2 weeks of initiation, as they can cause acute increases in creatinine (up to 30% is acceptable) and hyperkalemia, especially in advanced CKD. If blood pressure targets (typically <130/80 mmHg) aren't achieved with maximum tolerated doses, adding a calcium channel blocker like amlodipine (5-10 mg daily) or a thiazide-like diuretic such as chlorthalidone (12.5-25 mg daily) is recommended as second-line therapy. For patients with more advanced CKD (eGFR <30 ml/min), a loop diuretic like furosemide may be needed instead of thiazides.
Some key points to consider when managing hypertension in patients with diabetes and CKD include:
- Targeting an SBP of <120 mm Hg, as recommended by KDIGO, 1
- Using ACEIs or ARBs as first-line antihypertensive medications, as recommended by ADA/KDIGO, 1
- Monitoring serum creatinine and potassium levels when starting ACEIs or ARBs, as recommended by various guidelines
- Adding a calcium channel blocker or thiazide-like diuretic as second-line therapy if blood pressure targets are not achieved, as recommended by various guidelines.
The European Society of Cardiology guidelines, 1, also support the use of ACEIs or ARBs in patients with diabetes and hypertension, with a target blood pressure of <130/80 mmHg. Overall, the use of ACEIs or ARBs as first-line antihypertensive medications in patients with diabetes and CKD is supported by multiple guidelines and studies, including 1, 1, and 1.
From the FDA Drug Label
The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study involving 1513 patients treated with losartan or placebo, the overall incidences of reported adverse events were similar for the two groups. Discontinuations of losartan because of side effects were similar to placebo (19% for losartan, 24% for placebo) The adverse events, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with losartan and occurring with ≥2% difference in the losartan group vs placebo on a background of conventional antihypertensive therapy, were asthenia/fatigue, chest pain, hypotension, orthostatic hypotension, diarrhea, anemia, hyperkalemia, hypoglycemia, back pain, muscular weakness, and urinary tract infection.
The most optimal antihypertensive for someone with diabetes and chronic kidney disease is losartan, as it has been shown to be effective in reducing blood pressure and slowing the progression of kidney disease in patients with type 2 diabetes and nephropathy, as demonstrated in the RENAAL study 2.
- Key benefits of losartan include:
- Reduced risk of end-stage renal disease
- Slowed progression of kidney disease
- Effective in reducing blood pressure
- Well-tolerated with a similar side effect profile to placebo
- Important considerations:
- Monitor potassium levels and kidney function regularly
- Adjust dosage as needed to minimize side effects
- Consider combining with other antihypertensive agents if necessary to achieve blood pressure goals
From the Research
Optimal Antihypertensive Therapy
The optimal antihypertensive therapy for someone with diabetes and chronic kidney disease (CKD) involves the use of multiple agents to achieve blood pressure control and slow the progression of kidney disease.
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are traditional agents that have been used for 20 years to preserve kidney function 3.
- Sodium-glucose cotransporter 2 inhibitors have shown a potential class effect on improving renal outcomes, independent of their effect on glycemic parameters 3, 4, 5.
- Non-steroidal mineralocorticoid receptor antagonists, such as finerenone, have been approved for the management of CKD in people with type 2 diabetes 3, 4, 5.
Combination Therapy
Combination therapy is often necessary to achieve adequate blood pressure control in patients with CKD and diabetes.
- The use of ACEIs or ARBs in combination with a thiazide diuretic or a calcium channel blocker is recommended for patients with CKD and proteinuria 6.
- Losartan, an angiotensin-II-receptor antagonist, has been shown to reduce the incidence of a doubling of the serum creatinine concentration and end-stage renal disease in patients with type 2 diabetes and nephropathy 7.
Lifestyle Modifications and Glycemic Control
In addition to antihypertensive therapy, lifestyle modifications and glycemic control are important for managing CKD in patients with diabetes.
- Metformin and sodium-glucose cotransporter-2 inhibitors are first-line agents for glycemic control in patients with type 2 diabetes and CKD 4.
- Individualized HbA1c targets and cardiovascular disease risk reduction are also important considerations in the management of patients with type 2 diabetes and CKD 4.