Delaying Diabetic Kidney Disease Progression with SGLT2 Inhibitors and RAAS Blockade

Introduction to Therapeutic Framework

The American Diabetes Association recommends SGLT2 inhibitors as first-line therapy for all patients with diabetic kidney disease, regardless of baseline glucose control, to reduce the risk of kidney failure, dialysis, or renal death by 30-40% 1, 2, 3
The American College of Cardiology suggests that SGLT2 inhibitors simultaneously reduce cardiovascular death or heart failure hospitalization by 31% 1, 2

SGLT2 inhibitors reduce the risk of kidney failure, dialysis, or renal death by 30-40% even when added to maximum ACE inhibitor/ARB therapy, according to the American Heart Association 1, 2, 3
The CREDENCE trial with canagliflozin demonstrated a 30% reduction in the composite endpoint of chronic dialysis, kidney transplantation, sustained eGFR <15, doubling of serum creatinine, ESRD, or death from ESRD, as reported by the National Kidney Foundation 1, 2, 3

The American Diabetes Association recommends ACE inhibitors as the preferred first-line RAAS blocker for type 1 diabetes with any degree of albuminuria, while either ACE inhibitors or ARBs are appropriate for type 2 diabetes, to delay progression of nephropathy in hypertensive and normotensive patients 5, 6, 7
The National Institute of Diabetes and Digestive and Kidney Diseases suggests that ACE inhibitors have been shown to delay progression to macroalbuminuria in type 2 diabetes with microalbuminuria 5, 6, 7

The European Renal Association recommends finerenone to be added after SGLT2 inhibitor initiation if albuminuria persists, providing complementary anti-inflammatory and anti-fibrotic effects, to reduce the composite kidney outcome by 18% when added to ACE inhibitor/ARB therapy 3, 4
The FIDELIO-DKD trial demonstrated that finerenone reduced end-stage kidney disease by 36% in patients with moderately elevated albuminuria, as reported by the International Society of Nephrology 3, 4

The American College of Cardiology recommends optimizing glucose control with HbA1c target as close to 7% as safely possible without causing hypoglycemia, to reduce the risk and slow progression of diabetic kidney disease 5, 6, 7, 4
The American Heart Association suggests targeting blood pressure <130/80 mmHg for patients with diabetic kidney disease and albuminuria ≥30 mg/24 hours, to control blood pressure and slow progression 3, 8, 4

The National Kidney Foundation recommends requesting annual urine albumin-to-creatinine ratio (UACR) testing to guide therapy intensity and track treatment response, to reduce the risk of kidney failure, dialysis, or renal death 5, 6, 3, 4
The American Diabetes Association suggests measuring serum creatinine at least annually in all adults with diabetes to estimate GFR and stage chronic kidney disease, to track disease progression and treatment response 5, 6

The Academy of Nutrition and Dietetics recommends prescribing protein intake of 0.8-1.0 g/kg body weight/day for earlier stages of CKD, and 0.8 g/kg body weight/day for later stages, to slow GFR decline in selected patients once GFR begins falling 5, 7
The American College of Cardiology suggests continuing statin therapy for all adults ≥50 years with chronic kidney disease, to reduce cardiovascular risk 8, 4

The American Heart Association warns to never combine ACE inhibitors with ARBs, as this increases adverse events without additional benefits, according to the American College of Cardiology 4
The National Institute of Diabetes and Digestive and Kidney Diseases advises monitoring for hyperkalemia, as use of ACE inhibitors, ARBs, or finerenone may exacerbate hyperkalemia 5, 6, 7