The cornerstone of treatment of diabetic nephropathy involves glycemic control and blood pressure control. Blockade of the renin-angiotensin system with an ACE inhibitor or angiotensin receptor blocker (ARB) is recommended, typically to the maximal tolerated dose, because these agents both reduce blood pressure and levels of proteinuria, which, along with glycemic control, are the most important modifiable risk factors for progression of diabetic nephropathy to ESKD. Combined use of any two of the three renin-angiotensin system drug classes (ACE inhibitor, ARB, and direct renin inhibitor) is not recommended given the results of several clinical trials that revealed more adverse events with these combinations (hyperkalemia, hypotension, AKI), without additional cardiovascular or renal benefits. Combining ACE inhibitors or ARBs with mineralocorticoid receptors (spironolactone or eplerenone) has been shown in small studies to be a safe and effective antiproteinuric strategy in diabetic nephropathy, but the risk for hyperkalemia should be considered. For patients with type 2 diabetes and CKD, the American Diabetes Association recommends that physicians consider use of a sodium–glucose cotransporter 2 inhibitor when the estimated glomerular filtration rate is >30 mL/min/1.73 m2 with a urine albumin-creatinine ratio >30 mg/g. The recommendation is more strongly advised in patients with a higher-grade albuminuria (urine albumin-creatinine ratio >300 mg/g), in which the sodium–glucose cotransporter 2 inhibitor will reduce progression of kidney disease and/or cardiovascular events. In patients with CKD who have additional cardiovascular risk factors, a glucagon-like peptide 1 receptor agonist will also reduce the risk for CKD progression, cardiovascular events, or both.
The 2017 high blood pressure guideline from the American College of Cardiology (ACC), the American Heart Association (AHA), and nine other organizations recommends a blood pressure target of <130/80 mm Hg for patients with hypertension and diabetes mellitus and/or CKD. The American Diabetes Association recommends that most patients with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mm Hg and a diastolic blood pressure goal of <90 mm Hg; lower systolic and diastolic blood pressure targets, such as 130/80 mm Hg, may be appropriate for individuals at high risk of cardiovascular disease, if they can be achieved without undue treatment burden.